INDRA statements for KCNK2

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phosphosite cbn pc11 biopax bel_lc signor biogrid lincs_drug tas hprd trrust ctd virhostnet phosphoelm drugbank omnipath | geneways tees isi trips rlimsp medscan sparser eidos reach
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Arachidonic acid affects KCNK2
| 1 5 31
Arachidonic acid activates KCNK2.
| 1 5 28
Arachidonic acid activates KCNK2. 33 / 33
| 1 5 28
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"As shown in XREF_FIG, TREK-1 current was potentiated by 10muM arachidonic acid (AA) and application of SPA (10 -6 M) inhibited the AA activated TREK-1 current."
28105440
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"Since TREK and TRAAK channels are activated by arachidonic acid, it has been suggested that the mechanically sensitive phospholipase A 2 could mediate these effects XREF_BIBR although TRAAK mechanical activation is still possible in the presence of phospholipase A 2 inhibitors."
23691227
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"TRAAK, TREK-1, and TREK-2 channels are activated by arachidonic acid (AA)."
26919430
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"As shown in XREF_FIG, TREK-1 current was potentiated by 10muM arachidonic acid (AA) and application of SPA (10 -6 M) inhibited the AA activated TREK-1 current."
28105440
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"Swelling activated and arachidonic acid induced currents are TREK-1 in rat bladder smooth muscle cells."
26911303
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"Therefore, we suppose that the mechanical stretch due to the mastication activates phospholipase A (2) to release arachidonic acid (AA) from membrane, then, the released AA activates TREK-1."
17786632
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"The present study showed that treatment of uterine strips with TREK-1 channel inhibitor L-methionine insignificantly increased uterine contraction, while treatment with TREK-1 activator arachidonic acid caused a dramatic reduction in uterine contraction, suggesting that the TREK-1 is active and functional during pregnancy in rats."
29416642
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"Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels."
32317978
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"Although known as an inhibitor of many K + channels [13], AA also has been demonstrated to stimulate hEAG1 [16], Kir2.3 [17], and the TREK subfamily of K2P channels, including TREK-1, TREK-2, and TRAAK [18]."
30661462
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"The effect of cochlin was opposite to the well-known effects of shear stress stimulation by fluid flow or arachidonic acid (20microM), which significantly increased TREK-1 current by 72.1 +/-21.9% and 148.7 +/-50.1%, respectively (n = 5 each; Fig."
28352076
reach
"Our data suggest that the opening of background K (+) channels, like TREK-1 and TRAAK, which are activated by arachidonic acid and other polyunsaturated fatty acids such as docosahexaenoic acid and linolenic acid, is a significant factor in this neuroprotective effect."
10775263
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"Furthermore, as predicted based on arachidonic acid activation of both TREK-1 and TREK-2, some of the small molecules from this TREK-2 HTS were found to activate both TREK-1 and TREK-2."
27805811
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"In a number of experiments, we examined the action of AA on membrane patches, keeping in mind that AA could stimulate TREK-1 directly [21]."
30661462
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"Application of 10 muM arachidonic acid (AA) (free fatty acid) to cells expressing TREK-1 robustly activates TREK-1."
28793254
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"Application of arachidonic acid (10 mumol/L), chloroform (1 mmol/L) or etomidate (10 mumol/L) substantially increased TREK-1 channel currents in CHO and hTREK -1 cells."
27397543
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"Finally, we show that Glu306, an amino acid that has previously been found to be important in the modulation of TREK-1 by arachidonic acid, membrane stretch and internal pH, is critical for the activating effects of the anesthetic gases."
14742687
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"Therefore, we suppose that the mechanical stretch due to the mastication activates phospholipase A (2) to release arachidonic acid (AA) from membrane, then, the released AA activates TREK-1."
17786632
sparser
"TREK1, TREK2, and TRAAK are activated by arachidonic acid (AA) and other polyunsaturated fatty acids, such as docosahexaenoic acid and linoleic acid [ xref xref xref xref xref ]."
27790056
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"Arachidonic acid (an activator of TREK channels) had no effect on this conductance."
16265669
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"The activation of TREK-1 by AA and inhibition by forskolin were closely linked to membrane hyperpolarization and depolarization, respectively."
23858003
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"TREK1, TREK2, and TRAAK are activated by arachidonic acid (AA) and other polyunsaturated fatty acids, such as docosahexaenoic acid and linoleic acid [XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR]."
27790056
reach
"Application of 10 muM arachidonic acid (AA) (free fatty acid) to cells expressing TREK-1 robustly activates TREK-1."
28793254
sparser
"Our data suggest that the opening of background K(+) channels, like TREK-1 and TRAAK, which are activated by arachidonic acid and other polyunsaturated fatty acids such as docosahexaenoic acid and linolenic acid, is a significant factor in this neuroprotective effect."
10775263
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"Single channel recording via patch clamping showed that the TREK-1 outward currents in astrocytes could be activated by arachidonic acid (AA) or chloroform with the conductance of 113 +/-14 and 120 +/-13pS, respectively."
24402080
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"However, the addition of AA to cells can activate TREK-1 in seconds, and our lipidomics study incorporated AA over 15 min."
28793254
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"Similarly, arachidonic acid is suggested to activate TREK1 through incorporation in the outer leaflet of the bilayer XREF_BIBR and yet arachidonic does not stimulate TRPC5 XREF_BIBR."
19324410
sparser
"Arachidonic acid (AA) which is generated during CRH stimulation activates TREK-1 channels and causes hyperpolarization."
22225940
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"It is unlikely that block of phospholipase A 2 underlies the substantive effects on TREK and TRESK channels seen here, because arachidonic acid enhances TREK (and TRAAK) channels (Fink et al., 1996; Enyedi and Czirjak, 2010) and blocks TRESK channels (Sano et al., 2003; Kang et al., 2004)."
26914156
sparser
"The activation of TREK-1 by AA and inhibition by forskolin were closely linked to membrane hyperpolarization and depolarization, respectively."
23858003
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"Activation of TREK-1 by arachidonic acid (AA) is proposed to occur by a process linked to stretch activation (Brohawn, 2015)."
28242754
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"Importantly, in uterine strips treated simultaneously with progesterone and L-methionine, no significant reduction in uterine contraction was observed, and the uterine contraction was at levels similar to those in control tissues without progesterone or L-methionine treatment, suggesting opposing effects of L-methionine and progesterone on TREK-1 channel mediated uterine relaxation TREK-1 activator arachidonic acid causes no further effect on progesterone induced uterine relaxation."
29416642
sparser
"In inside-out patches, AA activated TRAAK, TREK-1, and TREK-2 channels with EC 50 values of 1.2 ± 0.1, 6.9 ± 1.2, and 3.8 ± 0.4 μM, respectively ( xref B and S6C)."
26919430
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"Mouse TREK-1 and TREK-2 channel currents were both significantly increased by AA, BL-1249, and CDC, similar to their human homologs."
32317978
Arachidonic acid inhibits KCNK2.
| 1
Arachidonic acid inhibits KCNK2. 1 / 1
| 1
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"TREK-1 inhibitor L-methionine partly reversed uterine relaxation caused by the progesterone, while TREK-1 activator arachidonic acid did not cause significant change in progesterone induced relaxation."
29416642
Arachidonic acid decreases the amount of KCNK2.
| 1
Arachidonic acid decreases the amount of KCNK2. 1 / 1
| 1
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"AA also rescued the decreased glutamate uptake and increased mRNA, as well as protein levels of GLT-1 and TREK-1."
27865879
Arachidonic acid binds KCNK2.
| 1
Arachidonic acid binds KCNK2. 1 / 1
| 1
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"We tested for direct binding of AA to TREK-1 and found both omega-3 and omega-6 AA (free fatty acid) competed with FL-PIP 2 (XREF_FIG)."
28793254
COCH affects KCNK2
| 1 15 19
COCH binds KCNK2.
| 1 15 12
COCH binds KCNK2. 26 / 26
| 1 14 12
sparser
"This data supports the idea that monomeric cochlin interacts with TREK-1 in the physiological environment causing a small increase in TREK-1 current resulting in a positive effect on outflow and a reduction in IOP."
28352076
reach
"Results presented here indicate that the interaction of TREK-1 and cochlin play an important role for maintaining IOP homeostasis. ""
28729644
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"Results presented here indicate that the interaction of TREK-1 and cochlin play an important role for maintaining IOP homeostasis."
28352076
reach
"We next probed functional interaction between cochlin and TREK-1 using the voltage sensitive dye, bis-(1, 3-dibutylbarbituric acid) trimethine oxonol (DiBAC)."
21886777
sparser
"To assess if cochlin interaction with TREK-1 also modulates the channel current, human TREK-1 was transiently expressed in HEK293 cells, and channel activity was monitored using whole-cell patch clamping."
28352076
sparser
"Taken together, these data suggest interaction of cochlin with TREK-1 is involved in formation of filopodia-like protrusions."
21886777
reach
"Voltage sensitive dye, bis-(1, 3-dibutylbarbituric acid) trimethine oxonol (DiBAC) intake studies XREF_BIBR further showed that TREK-1 interaction with cochlin is functional resulting in activation of TREK-1 channel and concomitant changes in TM cell shapes XREF_BIBR."
22496787
reach
"The interaction of cochlin and TREK-1 becomes an area of interest as both are components that seem to be needed for IOP regulation, as seen in the silencing experiments."
28352076
sparser
"This is consistent with the observation that similar amounts of cochlin are associated with greater amounts of TREK-1 in human TM samples, modeled through the application of shear stress (Fig.  xref )."
28352076
reach
"The TREK-1 and cochlin interaction is not sufficiently supported with the collagen gel assays and fluorescein transport assays alone but they lay the foundation for the remainder of our studies."
28352076
sparser
"These results suggest basement membrane proteins are elevated concomitant with secretion of cochlin in glaucomatous tissue and interaction of cochlin with TREK-1, stretch-activated channel (SAC) proteins and annexin A2 may mediate effects of cochlin."
21886777
sparser
"These observations are consistent with and corroborates our previous studies xref , xref , demonstrating similar changes in cell shape and interaction of multimerized cochlin with TREK-1 channels xref ."
28352076
sparser
"Previously, we postulated a model in which multimerized cochlin binding to TREK-1 changes cell shape and motility."
28352076
reach
"A direct or functional interaction of cochlin and TREK-1 remains to be demonstrated, however, a potential functional interaction between cochlin and TREK-1 may exist XREF_BIBR."
22496787
sparser
"A direct or functional interaction of cochlin and TREK-1 remains to be demonstrated, however, a potential functional interaction between cochlin and TREK-1 may exist xref ."
22496787
sparser
"The TREK-1 and cochlin interaction is not sufficiently supported with the collagen gel assays and fluorescein transport assays (Fig.  xref ) alone but they lay the foundation for the remainder of our studies."
28352076
sparser
"The interaction of cochlin and TREK-1 becomes an area of interest as both are components that seem to be needed for IOP regulation, as seen in the silencing experiments."
28352076
reach
"To assess if cochlin interaction with TREK-1 also modulates the channel current, human TREK-1 was transiently expressed in HEK293 cells, and channel activity was monitored using whole-cell patch clamping."
28352076
sparser
"The data presented here suggests that mechanical forces are possibly transmitted through cochlin-TREK-1 protein-protein interactions."
21886777
reach
"This data supports the idea that monomeric cochlin interacts with TREK-1 in the physiological environment causing a small increase in TREK-1 current resulting in a positive effect on outflow and a reduction in IOP."
28352076
reach
"Previously, we postulated a model in which multimerized cochlin binding to TREK-1 changes cell shape and motility."
28352076
reach
"Cochlin interacts with Annexin A2, SLC44A2, and potentially TREK-1."
28028002
sparser
"To investigate if the cochlin-TREK-1 interaction produced significant rearrangements in cellular organization within the TM cells, we measured fluorescein dye transport using an Ussing-type chamber across a trilayer of TM cells cultured on a PVDF membrane (Fig.  xref )."
28352076
sparser
"Interaction of cochlin and mechanosensitive channel TREK-1 in trabecular meshwork cells influences the regulation of intraocular pressure."
28352076
reach
"Our data, for the first time, suggests the involvement of an interaction of cochlin and TREK-1 in glaucoma and renders this interaction a target for therapy."
28352076
sparser
"Cochlin-TREK-1 interaction has functional consequences and results in changes in cell shape and motility."
21886777
COCH binds ANXA2 and KCNK2. 1 / 1
| 1
sparser
"Cochlin interacts with TREK-1 and annexin A2."
21886777
COCH inhibits KCNK2.
| 5
COCH inhibits KCNK2. 5 / 5
| 5
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"Multimeric cochlin induced a statistically significant decrease in TREK-1 current of 36.8 +/-11.2%; n = 5; p < 0.05 vs. baseline; Fig."
28352076
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"Physiological concentrations of multimeric but not monomeric cochlin reduce TREK-1 current."
28729644
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"TREK-1 basal channel activity was strongly reduced by multimerized cochlin at physiological concentrations (10nM)."
28352076
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"Physiological concentrations of multimeric but not monomeric cochlin reduce TREK-1 current."
28352076
reach
"In the diseased model, as supported by our data, multimerized cochlin decreases TREK-1 current, which may in turn decrease outflow, as a result of the cellular structure changes induced by the interaction of both proteins."
28352076
COCH activates KCNK2.
| 2
COCH activates KCNK2. 2 / 2
| 2
reach
"In fact, monomeric cochlin produced a small but significant increase in TREK-1 current, thus potentially favoring cell relaxation."
28352076
reach
"Multimeric cochlin modulates TREK-1 channel current."
28352076
KCNK2 affects COCH
| 1 15 13
KCNK2 binds COCH.
| 1 15 12
COCH binds KCNK2. 26 / 26
| 1 14 12
sparser
"This data supports the idea that monomeric cochlin interacts with TREK-1 in the physiological environment causing a small increase in TREK-1 current resulting in a positive effect on outflow and a reduction in IOP."
28352076
reach
"Results presented here indicate that the interaction of TREK-1 and cochlin play an important role for maintaining IOP homeostasis. ""
28729644
reach
"Results presented here indicate that the interaction of TREK-1 and cochlin play an important role for maintaining IOP homeostasis."
28352076
reach
"We next probed functional interaction between cochlin and TREK-1 using the voltage sensitive dye, bis-(1, 3-dibutylbarbituric acid) trimethine oxonol (DiBAC)."
21886777
sparser
"To assess if cochlin interaction with TREK-1 also modulates the channel current, human TREK-1 was transiently expressed in HEK293 cells, and channel activity was monitored using whole-cell patch clamping."
28352076
sparser
"Taken together, these data suggest interaction of cochlin with TREK-1 is involved in formation of filopodia-like protrusions."
21886777
reach
"Voltage sensitive dye, bis-(1, 3-dibutylbarbituric acid) trimethine oxonol (DiBAC) intake studies XREF_BIBR further showed that TREK-1 interaction with cochlin is functional resulting in activation of TREK-1 channel and concomitant changes in TM cell shapes XREF_BIBR."
22496787
reach
"The interaction of cochlin and TREK-1 becomes an area of interest as both are components that seem to be needed for IOP regulation, as seen in the silencing experiments."
28352076
sparser
"This is consistent with the observation that similar amounts of cochlin are associated with greater amounts of TREK-1 in human TM samples, modeled through the application of shear stress (Fig.  xref )."
28352076
reach
"The TREK-1 and cochlin interaction is not sufficiently supported with the collagen gel assays and fluorescein transport assays alone but they lay the foundation for the remainder of our studies."
28352076
sparser
"These results suggest basement membrane proteins are elevated concomitant with secretion of cochlin in glaucomatous tissue and interaction of cochlin with TREK-1, stretch-activated channel (SAC) proteins and annexin A2 may mediate effects of cochlin."
21886777
sparser
"These observations are consistent with and corroborates our previous studies xref , xref , demonstrating similar changes in cell shape and interaction of multimerized cochlin with TREK-1 channels xref ."
28352076
sparser
"Previously, we postulated a model in which multimerized cochlin binding to TREK-1 changes cell shape and motility."
28352076
reach
"A direct or functional interaction of cochlin and TREK-1 remains to be demonstrated, however, a potential functional interaction between cochlin and TREK-1 may exist XREF_BIBR."
22496787
sparser
"A direct or functional interaction of cochlin and TREK-1 remains to be demonstrated, however, a potential functional interaction between cochlin and TREK-1 may exist xref ."
22496787
sparser
"The TREK-1 and cochlin interaction is not sufficiently supported with the collagen gel assays and fluorescein transport assays (Fig.  xref ) alone but they lay the foundation for the remainder of our studies."
28352076
sparser
"The interaction of cochlin and TREK-1 becomes an area of interest as both are components that seem to be needed for IOP regulation, as seen in the silencing experiments."
28352076
reach
"To assess if cochlin interaction with TREK-1 also modulates the channel current, human TREK-1 was transiently expressed in HEK293 cells, and channel activity was monitored using whole-cell patch clamping."
28352076
sparser
"The data presented here suggests that mechanical forces are possibly transmitted through cochlin-TREK-1 protein-protein interactions."
21886777
reach
"This data supports the idea that monomeric cochlin interacts with TREK-1 in the physiological environment causing a small increase in TREK-1 current resulting in a positive effect on outflow and a reduction in IOP."
28352076
reach
"Previously, we postulated a model in which multimerized cochlin binding to TREK-1 changes cell shape and motility."
28352076
reach
"Cochlin interacts with Annexin A2, SLC44A2, and potentially TREK-1."
28028002
sparser
"To investigate if the cochlin-TREK-1 interaction produced significant rearrangements in cellular organization within the TM cells, we measured fluorescein dye transport using an Ussing-type chamber across a trilayer of TM cells cultured on a PVDF membrane (Fig.  xref )."
28352076
sparser
"Interaction of cochlin and mechanosensitive channel TREK-1 in trabecular meshwork cells influences the regulation of intraocular pressure."
28352076
reach
"Our data, for the first time, suggests the involvement of an interaction of cochlin and TREK-1 in glaucoma and renders this interaction a target for therapy."
28352076
sparser
"Cochlin-TREK-1 interaction has functional consequences and results in changes in cell shape and motility."
21886777
COCH binds ANXA2 and KCNK2. 1 / 1
| 1
sparser
"Cochlin interacts with TREK-1 and annexin A2."
21886777
KCNK2 activates COCH.
| 1
KCNK2 activates COCH. 1 / 1
| 1
reach
"The mechanosensitive channel TREK-1 could underlie cochlin mechanosensing."
28028002
Phosphatidylinositol phosphate affects KCNK2
| 5 17
Phosphatidylinositol phosphate inhibits KCNK2. 8 / 8
| 8
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"However, crude increases in PIP 2 concentration after initial activation have been shown to inactivate TREK-1 in cell culture, consistent with our direct PIP 2 antagonism playing a role in vivo."
28793254
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"Exogenous PIP 2 application was reported to reduce TREK1 response to various activating stimuli, including acidosis and membrane stretch."
20396900
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"Our assay shows PIP 2 binds with high affinity (0.87 muM) but surprisingly can directly antagonize TREK-1 in liposomes."
28793254
reach
"Because PIP 2 appears to antagonize TREK-1, it is unclear whether binding of small molecules is directly competing or if there are multiple conformations that lead to antagonism."
28793254
reach
"Our assay shows PIP 2 binds with high affinity (0.87 mM) but surprisingly can directly antagonize TREK-1 in liposomes."
28793254
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"These data, combined with previous studies of PLD2 activation of TREK-1, led us to propose a model where PIP 2 can directly antagonize TREK-1."
28793254
reach
"Channels like TREK-1 that are agonized by PA and directly inhibited by PIP 2 [XREF_BIBR] are likely the most affected since PEtOH and PIP 2 would combine to antagonize PA, and PA is in relatively low concentrations in the cell."
30529033
reach
"So why does PIP 2 antagonize TREK-1 in liposomes when PA and PG are activating?"
28793254
Phosphatidylinositol phosphate binds KCNK2. 7 / 7
| 4 3
sparser
"The opposite effect of low and high levels of PIP 2 in the presence of PG ( xref and xref ) may suggest multiple sites for PIP 2 binding to TREK-1."
28793254
reach
"Consistent with the ion flux data, ethanol had no effect on PIP 2 binding to TREK-1 or TRAAK (XREF_FIG) while norfluoxetine (NFX), a TREK-1 specific allosteric antagonist [XREF_BIBR], completely blocked PIP 2 binding (p < 0.0001) to TREK-1."
30529033
reach
"We show that PIP 2 directly binds to TREK-1 and competes with lipid agonists PA and phosphatidylglycerol (PG) in purified liposomes."
28793254
sparser
"To eliminate the potential artifacts from the luciferase enzyme or the fluorophore attached to the probe, we confirmed PIP 2 binding to TREK-1 in a radioactive version of the lipid binding assay using a tritiated ( 3 H) PIP 2 and a scintillation proximity assay (SPA). xref shows binding of 3 H-PIP 2 to detergent-purified TREK-1 channel; FL-PIP 2 dose-dependently competed with 3 H-PIP 2 (K d , 0.80 μM; Hill slope, −0.85) (see also xref )."
28793254
sparser
"To test PIP 2 binding to TREK-1, we fused a nanoluciferase (Nluc) to the C terminus of the channel and identified a soluble fluorescent PIP 2 (FL-PIP 2 ) analog suitable for binding to TREK-1. xref shows a cartoon of the assay design."
28793254
reach
"Given that our soluble binding assay shows that PIP 2 binds the channel, we reasoned PIP 2 could bind and antagonize TREK-1."
28793254
sparser
"Consistent with the ion flux data, ethanol had no effect on PIP 2 binding to TREK-1 or TRAAK ( xref ) while norfluoxetine (NFX), a TREK-1 specific allosteric antagonist[ xref ], completely blocked PIP 2 binding (p<0.0001) to TREK-1."
30529033
Phosphatidylinositol phosphate binds KCNK2 and KCNK4. 1 / 1
| 1
sparser
"Consistent with the ion flux data, ethanol had no effect on PIP 2 binding to TREK-1 or TRAAK ( xref ) while norfluoxetine (NFX), a TREK-1 specific allosteric antagonist[ xref ], completely blocked PIP 2 binding (p<0.0001) to TREK-1."
30529033
Phosphatidylinositol phosphate activates KCNK2. 6 / 6
| 6
reach
"Since TREK channels are activated by PIP 2 it is possible that the DCPIB effect is mediated via an allosteric enhancement of the PIP 2 effect rather than a direct competition with it."
26837888
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"In contrast with PG and PA, increasing concentrations of PIP 2 (0.5, 1, and 2 mol%) failed to activate TREK-1 : the highest concentration of PIP 2, 2 mol%, induced the least flux (XREF_FIG and XREF_FIG)."
28793254
reach
"These findings combined with Comoglio 's model of localization of PLD2 in the activation of TREK-1 suggest PIP 2 could indirectly activate TREK-1 through increasing PLD2 activation and production of PA and PG agonists (see XREF_SUPPLEMENTARY)."
28793254
reach
"As mentioned, PIP 2 could also indirectly activate TREK-1 through the enzyme PLD2."
28793254
reach
"Unexpectedly, sub-saturating PIP 2 (0.5 mol%) in the presence of 10 mol% PG enhanced TREK-1 activity (XREF_FIG and XREF_FIG)."
28793254
reach
"PIP 2 can also indirectly activate TREK-1 through PIP 2 agonism of PLD2 [XREF_BIBR], making PIP 2 regulation complicated [XREF_BIBR]."
30529033
KCNK2 affects cell population proliferation
| 8 14
KCNK2 activates cell population proliferation. 8 / 8
| 5 8
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"XREF_BIBR Overexpression of TREK-1 in healthy prostate epithelial cells increased their proliferation ability."
30863095
reach
"The fact that TREK-1 contributes to cell proliferation might in part explain our finding that TREK-1 expression was positively associated with GS and T staging."
25962960
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"The authors also found that TREK-1 blockers could inhibit cell proliferation of ovarian cancer cells through reducing early apoptosis and increasing late apoptosis."
25962960
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"XREF_BIBR In contrast, the knockdown of TREK-1 significantly inhibited the proliferation of prostate cancer cells."
30863095
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"Taken together, our results demonstrated that TREK-1 knockdown inhibited cell proliferation of PCa cells."
25962960
reach
"In addition, TREK-1 knockdown significantly attenuated prostate cancer cell proliferation both in vitro and in vivo."
28264681
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"Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell cycle arrest."
25962960
reach
"The two-pore domain K + channel, TREK1, increases proliferation of PC-3 and LNCaP prostate cancer cells."
23882223
KCNK2 inhibits cell population proliferation. 5 / 5
| 3 5
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"Over-expressed human TREK-1 inhibits CHO cell proliferation via inhibiting PKA and p38 MAPK pathways and subsequently inducing G1 arrest."
27397543
reach
"Bupivacaine and curcumin, two strong TREK-1 channel inhibitors, significantly increased embryonic NSC viability and proliferation while transfection of hTREK-1 decreased cell proliferation in embryonic NSCs."
21069514
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"The TREK-1 blocker curcumin reduced proliferation by 44% at 120 hrs at the highest concentration tested (XREF_FIG D), whereas L-methionine (XREF_FIG A) and L-methioninol, blockers of stretch dependent channels thought to be TREK-1, showed no effect (P> 0.05) on proliferation."
23305490
reach
"Moreover, blockages of TREK-1 by bupivacaine have been demonstrated to upregulate bone cell proliferation."
23425722
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"TREK-1 overexpression suppresses CHO cell proliferation by inhibiting the activity of PKA and p38 and MAPK signaling pathways and subsequently inducing G1 phase cell arrest."
27397543
Modified KCNK2 inhibits cell population proliferation. 1 / 1
| 1
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"Although the mechanism by which TREK-1 expression affects cellular functions remains unclear, it is believed, under hypoxic conditions, that the upregulation of TREK-1 expression inhibits the activity of protein kinase A and the expression of cyclin D1 [XREF_BIBR] and decreases neuronal stem cell [XREF_BIBR], astrocyte [XREF_BIBR], and human osteoblasts proliferation [XREF_BIBR, XREF_BIBR]."
28053983
COPB2 affects KCNK2
| 13
COPB2 binds KCNK2.
| 6
COPB2 binds KCNK2. 6 / 6
| 6
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"Several in vitro and in vivo binding assays confirmed the protein protein interaction between TREK1 and beta-COP."
20362547
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"The competitive inhibition assay revealed that the interaction between Flag-beta-COP and GFP-TREK1 was reduced dramatically with the addition of TREK1-N."
20362547
reach
"In addition, we confirmed the interaction between TREK1 and beta-COP under native conditions in PC3 prostate cancer cell, which highly expressed TREK1 channels [19]."
20362547
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"To investigate the interaction between TREK1 and beta-COP in vivo, N-terminal tagged vectors expressing Flag tagged TREK1 (Flag-TREK1) and GFP tagged beta-COP (GFP-beta-COP) were co-transfected into HEK293T cells."
20362547
reach
"The protein protein interaction between TREK1 and beta-COP was confirmed using the yeast two-hybrid and GST pull-down assays."
20362547
reach
"The direct binding of beta-COP with TREK1 in vivo was strongly supported by Immunoprecipitation experiment with an anti-TREK1 antibody in PC3 cells and by the co-localization of RFP-beta-COP with GFP-TREK1 at the plasma membrane of COS-7 cells."
20362547
COPB2 increases the amount of KCNK2.
| 3
COPB2 increases the amount of KCNK2. 3 / 3
| 3
reach
"Cell-surface expression of TREK1 (HA) was also increased over 90% by beta-COP."
20362547
reach
"The COPI complex is reportedly involved in the anterograde and retrograde transport of various proteins [16], and beta-COP has been shown to directly bind to the N-terminus and enhance the expression of TREK1 (KCNK2), which is a member of the KCNK channel protein family [16]."
27207835
reach
"Cell-surface biotinylation experiments clearly showed that beta-COP increased the surface expression of TREK1."
20362547
COPB2 activates KCNK2.
| 2
COPB2 activates KCNK2. 2 / 2
| 2
reach
"Beta-COP promoted surface expression and whole-cell currents of TREK1."
20362547
reach
"These results indicated that beta-COP enhances the channel activity and surface expression of TREK1 via the protein protein interaction with its N-terminal region in vivo."
20362547
COPB2 inhibits KCNK2.
| 1
COPB2 inhibits KCNK2. 1 / 1
| 1
reach
"Moreover, beta-COP shRNA inhibited plasma membrane localization of the TREK1 channel significantly."
20362547
COPB2 decreases the amount of KCNK2.
| 1
COPB2 decreases the amount of KCNK2. 1 / 1
| 1
reach
"In addition, beta-COP shRNA inhibited surface expression of the TREK channels significantly."
20362547
PKA affects KCNK2
| 6 6
PKA phosphorylates KCNK2.
| 3 4
PKA phosphorylates KCNK2. 7 / 7
| 3 4
sparser
"It has also been suggested that PKA phosphorylates TREK1 and converts it into a voltage-dependent channel xref ."
24086441
reach
"It has also been suggested that PKA phosphorylates TREK1 and converts it into a voltage dependent channel XREF_BIBR."
24086441
reach
"PKA directly phosphorylates TRPV1 and the heat sensitive potassium channel TREK, and in both cases, this phosphorylation modulates the electrophysiological properties of the channel."
15249591
sparser
"PKA directly phosphorylates TRPV1 and the heat-sensitive potassium channel TREK ( xref , xref , xref ), and in both cases, this phosphorylation modulates the electrophysiological properties of the channel."
15249591
sparser
"In addition, phosphorylation of TREK-1 by protein kinase A or C can results in channel inactivation."
11165377
reach
"In addition to its role in adipocyte differentiation, some reports indicate that PKA phosphorylates the COOH terminal region of the TREK subfamily and inhibits channel activity [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
25501330
reach
"In addition, phosphorylation of TREK-1 by protein kinase A or C can results in channel inactivation."
11165377
PKA inhibits KCNK2.
| 2 1
PKA inhibits KCNK2. 3 / 3
| 2 1
sparser
"These findings demonstrate that, in addition to the well-described PKA-dependent TREK-1 inhibition, ACTH, NPS-ACTH, forskolin, and 8-pCPT-2′-O-Me-cAMP also inhibit these K + channels by a PKA-independent signaling pathway."
18663135
reach
"TREK-1 activation, unlike TRAAK, is reversed by protein kinase A and protein kinase C stimulation [18,19 **,20,24 **,27,30 **]."
11454447
sparser
"The inhibitory process is attributable to an increase of the intracellular cAMP concentration by riluzole that produces a protein kinase A-dependent inhibition of TREK-1."
10779373
PKA binds KCNK2.
| 1
PKA binds KCNK2. 1 / 1
| 1
sparser
"Previous studies have described an interaction between Popeye domain‐containing proteins (Popdc1 and Popdc2) and TREK‐1 that is important for its regulation by protein kinase A, with implications for pacemaking in the mouse. xref Similarly, even earlier work identified an association between TREK‐1 and A kinase anchor protein 150 that controls response of channel to Gs‐coupled receptor activation. xref Our new findings together with our previous work xref indicate that β IV ‐spectrin associates with TREK‐1 and is essential for its proper membrane targeting in myocytes throughout the heart."
27098968
PKA activates KCNK2.
| 1
PKA activates KCNK2. 1 / 1
| 1
reach
"The inhibitory process is attributable to an increase of the intracellular cAMP concentration by riluzole that produces a protein kinase A dependent inhibition of TREK-1."
10779373
KCNK2 affects BDNF
| 1 11
KCNK2 decreases the amount of BDNF.
| 6
Modified KCNK2 decreases the amount of BDNF. 3 / 3
| 3
reach
"XREF_FIG, we found that the knockdown of TREK-1 increased BDNF expression and that the over-expression of TREK-1 decreased the level of BDNF with increasing doses of isoflurane."
28870160
reach
"As demonstrated in XREF_FIG, Plenti-TREK-1-GFP infection significantly increased TREK-1 expression in astrocytes compared with Plenti-sham-GFP infection cells (P < 0.05), and TREK-1 overexpression exhibited similar effects to the isoflurane dependent changes in the expression of BDNF, Bax and caspase-3, as TREK-1 overexpression reduced the expression of BDNF, and increased the expression of Bax and caspase-3, which was also observed for isoflurane treatment in XREF_FIG."
28944872
reach
"However, TREK-1 overexpression in astrocytes significantly downregulated BDNF expression, and upregulated Bax and caspase-3 expression."
28944872
KCNK2 decreases the amount of BDNF. 3 / 3
| 3
reach
"XREF_FIG, we found that the knockdown of TREK-1 increased BDNF expression and that the over-expression of TREK-1 decreased the level of BDNF with increasing doses of isoflurane."
28870160
reach
"To our surprise, the knockdown of TREK-1 in astrocytes induced a significant increase in the expression of BDNF after treating with 2.4% isoflurane compared with expression in the vector group, but this increase was nonsignificant with the administration of 3.6%, possibly because the inhibitory effects of isoflurane at this high dose were so strong that the knockdown of TREK-1 could not rescue the expression of BDNF."
28870160
reach
"TREK-1 negatively regulated BDNF expression during isoflurane induced astrocytic toxicity."
28870160
KCNK2 inhibits BDNF.
| 3
KCNK2 inhibits BDNF. 3 / 3
| 3
reach
"We also found TREK-1 blockade could enhance the synthesis of BDNF in astrocytes, which might be important in neuroprotection [21]."
29438799
reach
"Furthermore, overexpression of TREK-1 in astrocytes downregulated BDNF, and upregulated Bax and caspase-3, while TREK-1 shRNA effectively reversed the isoflurane dependent changes in BDNF, Bax and caspase-3 expression."
28944872
reach
"Overexpression of TREK-1 downregulates BDNF, and upregulates Bax and caspase-3."
28944872
KCNK2 binds BDNF.
| 1 1
BDNF binds KCNK2. 2 / 2
| 1 1
sparser
"Taken together, the results of the present study indicate that isoflurane-induced cell damage in astrocytes may be associated with TREK-1-mediated inhibition of BDNF and provide a reference for the safe use of isoflurane anesthesia in infants and children."
28944872
reach
"To investigate the downstream mechanism responsible for the neuroprotective effects elicited by TREK-1 inhibition in isoflurane induced astrocytic cytotoxicity, we analysed the association between TREK-1 and BDNF."
28870160
KCNK2 increases the amount of BDNF.
| 1
KCNK2 increases the amount of BDNF. 1 / 1
| 1
reach
"The inhibition and over-expression of TREK-1 tended to up- and down-regulate, respectively, the expression of BDNF."
28870160
3',5'-cyclic AMP affects KCNK2
| 11
3',5'-cyclic AMP inhibits KCNK2.
| 8
3',5'-cyclic AMP inhibits KCNK2. 8 / 8
| 8
reach
"Accordingly, it was previously reported that TREK-1 inhibition by cAMP is voltage dependent and less effective at positive potentials."
23858003
reach
"Because cAMP analogs inhibited increase of the PDBu elicited K2P currents produced by divalent cataions, we suggest that cAMP may inhibit TREK1 channel without PKA activation."
24086441
reach
"The decrease in cAMP concentration (as a result of reduced adenylate cyclase activity) in 5-HT neurons is also thought to induce TREK-1 opening because of a consequent reduction of phosphorylation of Ser333 by PKA XREF_BIBR."
20405001
reach
"TREK-1 and TREK-2 (which was not represented on the original Affymetrix chip) are inhibited by cAMP via PKA and exhibit outward rectification in physiological solutions [XREF_BIBR]."
17643200
reach
"Previously, it had been shown that TREK-1 inhibition by cAMP was voltage dependent and less effective at positive potentials."
23858003
reach
"This hypothesis is supported by an earlier report that suggested that cAMP might inhibit the TREK1 channel independently from PKA in bovine adrenal zona fasciculata cells XREF_BIBR."
24086441
reach
"In this regard, of the 15 members of the K2P K + channels family, only TREK-1 and TREK-2 are inhibited by cAMP."
23858003
reach
"Adrenocorticotropic hormone and cAMP may inhibit TREK-1 by a PKA independent signaling pathway XREF_BIBR."
24086441
3',5'-cyclic AMP activates KCNK2.
| 3
3',5'-cyclic AMP activates KCNK2. 3 / 3
| 3
reach
"Interestingly, as outlined in Table 5, a vast majority of identified binding and reaction partners of AKAP5 is altered in BD, being either up-regulated (cAMP dependent protein kinase A and its regulatory subunit II, calmodulin 1, GTPase activating protein 1 and TREK-1), or down-regulated (PSD95; NMDA-type glutamate receptor 2B and beta-adrenergic receptor), or represent susceptibility genes for BD (SAP97, calcineurin, AMPA-type glutamate receptor)."
23462372
reach
"In addition, cAMP was supposed to negatively modulate the interaction of TREK-1 with POPDC proteins."
30863095
reach
"Interestingly, cAMP analogs have been reported to enhance TREK1 mRNA independently from PKA in adrenocortical cells XREF_BIBR."
24086441
KCNK2 affects COPB1
| 10
COPB1 binds KCNK2. 9 / 9
| 9
sparser
"The direct binding of β-COP with TREK1 in vivo was strongly supported by Immunoprecipitation experiment with an anti-TREK1 antibody in PC3 cells ( Fig. 2 C) and by the co-localization of RFP-β-COP with GFP-TREK1 at the plasma membrane of COS-7 cells ( Fig. 2 D)."
20362547
sparser
"In this study, we demonstrated for the first time that β-COP directly interacts with N-terminal region of TREK1."
20362547
sparser
"We present that the first interacting molecule, β-COP, directly interacting with N-terminal region of TREK1."
20362547
sparser
"To investigate the interaction between TREK1 and β-COP in vivo , N-terminal tagged vectors expressing Flag-tagged TREK1 (Flag-TREK1) and GFP-tagged β-COP (GFP-β-COP) were co-transfected into HEK293T cells."
20362547
sparser
"Especially, we clearly showed that β-COP was associated with TREK1 in native condition at the PC3 cells ( Fig. 2 C)."
20362547
sparser
"In this study, we provide an evidence for a direct protein–protein interaction between β-COP, a subunit of Coat Protein Complex I (COPI), and the TREK1 channel."
20362547
sparser
"The protein–protein interaction between TREK1 and β-COP was confirmed using the yeast two-hybrid and GST pull-down assays."
20362547
sparser
"Based on these data, we concluded that β-COP can directly bind with the N-terminal region of TREK1 channels."
20362547
sparser
"This protein–protein interaction between β-COP and TREK1 channel was confirmed by several in vitro assays and in vivo assays ( Figs."
20362547
COPB1 binds KCNK2, Akap5, and Mtap2. 1 / 1
| 1
sparser
"Also, bindings of AKAP150 (A-Kinase-Anchoring Protein), Mtap2 (Microtubule-Associated Protein 2) and β-COP (Coat Protein Complex) to TREK channels enhance surface expression [19] ."
28676394
Isoflurane affects KCNK2
| 2 9
Isoflurane increases the amount of KCNK2.
| 4
Isoflurane increases the amount of KCNK2. 4 / 4
| 4
reach
"The present study suggested that isoflurane exposure increased the TREK1 expression in spinal cord ischemic injury rats."
27469140
reach
"Isoflurane exposure decreases BDNF levels and increases Bax, caspase-3 and TREK-1 expression in astrocytes."
28944872
reach
"This study suggested that isoflurane pre-conditioning activated TREK1 expression in ischemic spinal cord injury rats, which may suppress apoptosis."
28480032
reach
"The results of the current study indicate that isoflurane administration in vitro significantly upregulated TREK-1 expression in astrocytes."
28944872
Isoflurane activates KCNK2.
| 2 4
Isoflurane activates KCNK2. 4 / 4
| 2 4
reach
"Notably, TREK-1 is activated by clinical concentrations of isoflurane, and is involved in the effects of isoflurane preconditioning."
28944872
reach
"XREF_BIBR examined TASK and TREK-1, and found that TREK-1 was activated by chloroform, diethyl ether, halothane and isoflurane, while TASK was activated by halothane and isoflurane."
20735416
reach
"These results indicate that isoflurane administration may promote TREK-1 activity and apoptosis in astrocytes, and inhibit BDNF expression."
28944872
reach
"Chloroform, diethyl ether, halothane and isoflurane activated TREK-1, whereas only halothane and isoflurane activated TASK."
10321245
Isoflurane decreases the amount of KCNK2.
| 1
Isoflurane decreases the amount of KCNK2. 1 / 1
| 1
reach
"Isoflurane exposure decreases BDNF levels and increases Bax, caspase-3 and TREK-1 expression in astrocytes."
28944872
KCNK2 affects Akap5
| 7 2
KCNK2 binds Akap5. 5 / 5
| 3 2
sparser
"The association of AKAP150 with TREK channels integrates them into a postsynaptic scaffold where both G-protein-coupled membrane receptors (as demonstrated here for beta2AR) and TREK-1 dock simultaneously."
17110924
reach
"Inhibition of the TREK-1 and AKAP150 complex by Gs coupled receptors such as serotonin 5HT4sR and noradrenaline beta2AR is as extensive as for TREK-1 alone, but is faster."
17110924
sparser
"Recently, we demonstrated that A-kinase anchoring protein AKAP150 binds to a major regulatory domain of TREK-1, promoting drastic changes in channel regulation by polyunsaturated fatty acids, pH, and stretch, and by G-protein-coupled receptors to neurotransmitters and hormones."
18716213
reach
"Mtap2 and AKAP150 can bind to TREK-1 simultaneously and modulate the channel synergistically."
26772438
sparser
"Furthermore, the association of AKAP150 with TREK1 channels integrates them into postsynaptic scaffolds where G protein-coupled membrane receptors and channels dock simultaneously."
18998088
KCNK2 binds Akap5 and Mtap2. 3 / 3
| 3
sparser
"TREK Channel Interactions with AKAP150 and Mtap2."
21358977
sparser
"Mtap2 and AKAP150 can bind to TREK-1 simultaneously and modulate the channel synergistically ( xref )."
26772438
sparser
"In particular, AKAP150 and Mtap2 interact simultaneously with the C-terminus of TREK1 and enhance cell-surface expression and activation of the channel [15] ."
20362547
COPB1 binds KCNK2, Akap5, and Mtap2. 1 / 1
| 1
sparser
"Also, bindings of AKAP150 (A-Kinase-Anchoring Protein), Mtap2 (Microtubule-Associated Protein 2) and β-COP (Coat Protein Complex) to TREK channels enhance surface expression [19] ."
28676394
Spadin affects KCNK2
| 8
Spadin inhibits KCNK2.
| 6
Spadin inhibits KCNK2. 6 / 6
| 6
reach
"Furthermore, spadin was unable to prevent activation of TREK-1 by BL-1249, CDC, or the related bioactive lipid, DHA."
32317978
reach
"Here, we showed that spadin blocked TREK-1 current exactly as it did for the transiently transfected TREK-1 channels (XREF_FIG)."
22022421
reach
"Moreover, spadin blocks TREK-1 with higher affinity, IC 50 ~ 40-60 nM vs. IC 50 ~ 6 muM for the most used SSRI fluoxetine."
28955242
reach
"Electrophysiological studies show that spadin efficiently blocks the TREK-1 activity in COS-7 cells, cultured pyramidal neurons, as well as CA3 hippocampal neurons in brain slices of wild-type mice and not in kcnk2 -/- mice, suggesting a specific effect of spadin on the TREK-1 channel."
20405001
reach
"Direct inhibition of TREK-1 by spadin may also contribute to enhanced 5-HT neuron excitability."
20405001
reach
"Electrophysiological studies showed that spadin efficiently blocked the TREK-1 activity in COS-7 cells, cultured hippocampal pyramidal neurons, and CA3 hippocampal neurons in brain slices."
20405001
Spadin binds KCNK2.
| 2
KCNK2 binds spadin. 2 / 2
| 2
reach
"XREF_FIG shows that spadin bound specifically to TREK-1 with an affinity of about 10 nM."
20405001
reach
"Taken together, these results indicate that TREK-1 and NTSR3 and Sortilin are not only associated within the plasma membrane but that spadin interacts directly with TREK-1 to functionally inhibit its activity."
20405001
KCNK2 affects phosphatidylinositol phosphate
| 5 3
Phosphatidylinositol phosphate binds KCNK2. 7 / 7
| 4 3
sparser
"The opposite effect of low and high levels of PIP 2 in the presence of PG ( xref and xref ) may suggest multiple sites for PIP 2 binding to TREK-1."
28793254
reach
"Consistent with the ion flux data, ethanol had no effect on PIP 2 binding to TREK-1 or TRAAK (XREF_FIG) while norfluoxetine (NFX), a TREK-1 specific allosteric antagonist [XREF_BIBR], completely blocked PIP 2 binding (p < 0.0001) to TREK-1."
30529033
reach
"We show that PIP 2 directly binds to TREK-1 and competes with lipid agonists PA and phosphatidylglycerol (PG) in purified liposomes."
28793254
sparser
"To eliminate the potential artifacts from the luciferase enzyme or the fluorophore attached to the probe, we confirmed PIP 2 binding to TREK-1 in a radioactive version of the lipid binding assay using a tritiated ( 3 H) PIP 2 and a scintillation proximity assay (SPA). xref shows binding of 3 H-PIP 2 to detergent-purified TREK-1 channel; FL-PIP 2 dose-dependently competed with 3 H-PIP 2 (K d , 0.80 μM; Hill slope, −0.85) (see also xref )."
28793254
sparser
"To test PIP 2 binding to TREK-1, we fused a nanoluciferase (Nluc) to the C terminus of the channel and identified a soluble fluorescent PIP 2 (FL-PIP 2 ) analog suitable for binding to TREK-1. xref shows a cartoon of the assay design."
28793254
reach
"Given that our soluble binding assay shows that PIP 2 binds the channel, we reasoned PIP 2 could bind and antagonize TREK-1."
28793254
sparser
"Consistent with the ion flux data, ethanol had no effect on PIP 2 binding to TREK-1 or TRAAK ( xref ) while norfluoxetine (NFX), a TREK-1 specific allosteric antagonist[ xref ], completely blocked PIP 2 binding (p<0.0001) to TREK-1."
30529033
Phosphatidylinositol phosphate binds KCNK2 and KCNK4. 1 / 1
| 1
sparser
"Consistent with the ion flux data, ethanol had no effect on PIP 2 binding to TREK-1 or TRAAK ( xref ) while norfluoxetine (NFX), a TREK-1 specific allosteric antagonist[ xref ], completely blocked PIP 2 binding (p<0.0001) to TREK-1."
30529033
KCNK2 affects apoptotic process
| 8
KCNK2 inhibits apoptotic process.
| 6
KCNK2 inhibits apoptotic process. 6 / 6
| 6
reach
"The over-expression of TREK1 could decrease apoptosis and NADH in neurons."
27469140
reach
"Kcnk2 overexpression enhanced the viability and inhibited the apoptosis of the H/R treated PC12 cells."
31959866
reach
"In addition, upregulation of Kcnk2 or knockdown of Foxd3 promoted the cell viability and reduced the apoptosis of the H/R treated PC12 cells."
31959866
reach
"However, blockade of TREK1 channels raised the number of hypoxia induced neuronal apoptosis in a neuron-astrocyte co-culture indicating a neuroprotective role of TREK1 channels after hypoxia [XREF_BIBR]."
24373160
reach
"Taken together, this result indicated that the over-expression of TREK1 might reduce the apoptosis of neurons to play a role of neuroprotection."
27469140
reach
"The results indicated that TREK1 could decrease neurons apoptosis caused by hypoxia or ischemia."
27469140
KCNK2 activates apoptotic process.
| 2
KCNK2 activates apoptotic process. 2 / 2
| 2
reach
"TREK-1 deficiency promoted apoptosis in HO exposed lungs."
25126877
reach
"Furthermore, in an in vivo model of Acute Lung Injury (ALI) we recently found that TREK-1 deficiency led to increased lung damage and AEC apoptosis but decreased BAL cytokine levels [XREF_BIBR]."
26001192
TKDC affects KCNK2
| 7
TKDC inhibits KCNK2.
| 4
TKDC inhibits KCNK2. 4 / 4
| 4
reach
"Inhibition of TREK channels by TKDC."
28851868
reach
"In contrast, the application of TKDC to the intracellular side of the channel did not significantly inhibit TREK-1 activity."
28851868
reach
"We then investigated whether other TREK subfamily members were also inhibited by TKDC."
28851868
reach
"The application of TKDC to the extracellular face of the membrane (outside-out recording) consistently inhibited TREK-1."
28851868
TKDC binds KCNK2.
| 2
KCNK2 binds TKDC. 2 / 2
| 2
reach
"In the S complex simulations, the interactions between TKDC and TREK-1 were stable."
28851868
reach
"A TREK-1 and TKDC complex simulation system (termed S complex) was built by inserting the docking model of TREK-1 and TKDC into an explicit membrane environment."
28851868
TKDC activates KCNK2.
| 1
TKDC activates KCNK2. 1 / 1
| 1
reach
"Compared with the DMSO control, TKDC did not significantly increase TREK-1 internalization."
28851868
POMC affects KCNK2
| 3 4
POMC inhibits KCNK2.
| 3 3
POMC inhibits KCNK2. 6 / 6
| 3 3
reach
"This leak-type K + channel, later identified as TREK-1 of the two-pore K + (K2P) channel family, was potently inhibited by ACTH and AngII, leading directly to membrane depolarization."
23858003
sparser
"In contrast to forskolin, the inhibition of TREK-1 by ACTH was voltage independent."
23858003
sparser
"Adrenocorticotropic hormone and cAMP may inhibit TREK-1 by a PKA-independent signaling pathway xref ."
24086441
reach
"In contrast to forskolin, the inhibition of TREK-1 by ACTH was voltage independent."
23858003
sparser
"Second, TREK-1 inhibition by NPS-ACTH was insensitive to PKA inhibitors."
18663135
reach
"Adrenocorticotropic hormone and cAMP may inhibit TREK-1 by a PKA independent signaling pathway XREF_BIBR."
24086441
POMC decreases the amount of KCNK2.
| 1
POMC decreases the amount of KCNK2. 1 / 1
| 1
reach
"The putative TREK-1 current expressed by human AZF cells was potently and effectively inhibited by ACTH (XREF_FIG)."
23858003
PLD2 affects KCNK2
| 1 3 4
PLD2 binds KCNK2.
| 2 1
KCNK2 binds PLD2. 2 / 2
| 2
sparser
"PA appears to activate TREK-1 as phospholipase D2 (PLD2) directly binds to TREK-1 and activates the channel through local production of lipid ( xref )."
28793254
sparser
"PA and PG are both products of the enzyme PLD2 ( xref ), and we expect these lipids to agonize the channel as PLD2 binds directly to the C terminus of TREK-1 and activates the channel ( xref ) (see also xref )."
28793254
KCNK2 binds PLD2 and phospholipase. 1 / 1
| 1
reach
"PA appears to activate TREK-1 as phospholipase D2 (PLD2) directly binds to TREK-1 and activates the channel through local production of lipid."
28793254
PLD2 activates KCNK2.
| 1 1 2
PLD2 activates KCNK2. 3 / 3
| 1 1 2
reach
"Even though all three of the channels are sensitive to PA, we found that only TREK1 and TREK2 are potentiated by PLD2 and that none of these channels is modulated by PLD1, indicating surprising selectivity."
25197053
reach
"These data, combined with previous studies of PLD2 activation of TREK-1, led us to propose a model where PIP 2 can directly antagonize TREK-1."
28793254
sparser
"These data, combined with previous studies of PLD2 activation of TREK-1 ( xref ), led us to propose a model where PIP 2 can directly antagonize TREK-1."
28793254
PLD2 inhibits KCNK2.
| 1
PLD2 inhibits KCNK2. 1 / 1
| 1
reach
"The lack of PLD2 activity indirectly inhibited TREK-1 currents."
31124840
Mtap2 affects KCNK2
| 5 2
KCNK2 binds Akap5 and Mtap2. 3 / 3
| 3
sparser
"TREK Channel Interactions with AKAP150 and Mtap2."
21358977
sparser
"Mtap2 and AKAP150 can bind to TREK-1 simultaneously and modulate the channel synergistically ( xref )."
26772438
sparser
"In particular, AKAP150 and Mtap2 interact simultaneously with the C-terminus of TREK1 and enhance cell-surface expression and activation of the channel [15] ."
20362547
KCNK2 binds Mtap2. 2 / 2
| 2
reach
"Mtap2 and AKAP150 can bind to TREK-1 simultaneously and modulate the channel synergistically."
26772438
reach
"Mtap2 binding to TREK-1 and TREK-2 does not affect directly channel properties but enhances channel surface expression and current density."
18716213
KCNK10 binds KCNK2 and Mtap2. 1 / 1
| 1
sparser
"Mtap2 binding to TREK-1 and TREK-2 does not affect directly channel properties but enhances channel surface expression and current density."
18716213
COPB1 binds KCNK2, Akap5, and Mtap2. 1 / 1
| 1
sparser
"Also, bindings of AKAP150 (A-Kinase-Anchoring Protein), Mtap2 (Microtubule-Associated Protein 2) and β-COP (Coat Protein Complex) to TREK channels enhance surface expression [19] ."
28676394
KCNK2 affects MCP-1
| 7
KCNK2 activates MCP-1.
| 5
KCNK2 activates MCP-1. 5 / 5
| 5
reach
"We recently reported the expression of K2P channels in alveolar epithelial cells (AECs) and found that TNF-alpha stimulation of TREK-1 deficient AECs caused decreased IL-6 secretion but increased MCP-1 secretion in vitro [XREF_BIBR, XREF_BIBR]."
25126877
reach
"We found that TREK-1 deficiency altered the cytokine release profile of alveolar epithelial cells upon TNF-alpha stimulation, resulting in decreased IL-6 and increased MCP-1 secretion [XREF_BIBR, XREF_BIBR]."
25126877
reach
"In summary, we report for the first time that TREK-1 deficiency in human AECs resulted in increased MCP-1 production and secretion, and this effect appeared unrelated to alterations in JNK-, PKC- or Ca (2+)-mediated signaling pathways in TREK-1 deficient cells."
23977412
reach
"Interestingly, while TREK-1 deficiency resulted in decreased IL-6 and increased MCP-1 secretion from both mouse [XREF_BIBR] and human alveolar epithelial cells [XREF_BIBR, XREF_BIBR], overexpression of TREK-1 had no further effect on MCP-1 secretion when compared to control cells [XREF_BIBR]."
26001192
reach
"In contrast to IL-6 secretion, we found that TREK-1 deficiency resulted in increased MCP-1 production and secretion, although baseline MCP-1 gene expression was unchanged in TREK-1 deficient cells."
23977412
KCNK2 increases the amount of MCP-1.
| 2
KCNK2 increases the amount of MCP-1. 2 / 2
| 2
reach
"As noted previously [XREF_BIBR], at baseline and after TNF-alpha stimulation, TREK-1 deficient cells secreted increased amounts of MCP-1 when compared to control cells (XREF_FIG and XREF_FIG)."
26001192
reach
"Our data revealed that TREK-1 deficient AECs secrete lower amounts of IL-6 but increased amounts of MCP-1 upon TNF-alpha stimulation [XREF_BIBR - XREF_BIBR]."
26001192
KCNK2 affects CASP3
| 7
KCNK2 increases the amount of CASP3.
| 3
Modified KCNK2 increases the amount of CASP3. 2 / 2
| 2
reach
"However, TREK-1 overexpression in astrocytes significantly downregulated BDNF expression, and upregulated Bax and caspase-3 expression."
28944872
reach
"As demonstrated in XREF_FIG, Plenti-TREK-1-GFP infection significantly increased TREK-1 expression in astrocytes compared with Plenti-sham-GFP infection cells (P < 0.05), and TREK-1 overexpression exhibited similar effects to the isoflurane dependent changes in the expression of BDNF, Bax and caspase-3, as TREK-1 overexpression reduced the expression of BDNF, and increased the expression of Bax and caspase-3, which was also observed for isoflurane treatment in XREF_FIG."
28944872
KCNK2 increases the amount of CASP3. 1 / 1
| 1
reach
"Furthermore, lentiviral mediated short hairpin RNA knockdown of TREK-1 effectively inhibited the isoflurane induced changes in BDNF, Bax and caspase-3 expression."
28944872
KCNK2 activates CASP3.
| 2
KCNK2 activates CASP3. 2 / 2
| 2
reach
"Overexpression of TREK-1 downregulates BDNF, and upregulates Bax and caspase-3."
28944872
reach
"Furthermore, overexpression of TREK-1 in astrocytes downregulated BDNF, and upregulated Bax and caspase-3, while TREK-1 shRNA effectively reversed the isoflurane dependent changes in BDNF, Bax and caspase-3 expression."
28944872
KCNK2 inhibits CASP3.
| 1
KCNK2 inhibits CASP3. 1 / 1
| 1
reach
"On the other hand, TREK1 silence (si-TREK1) significantly increased the caspase-3 activity and percentage of sub-G1 cells (p < 0.05)."
27469140
KCNK2 decreases the amount of CASP3.
| 1
Modified KCNK2 decreases the amount of CASP3. 1 / 1
| 1
reach
"As demonstrated in XREF_FIG, Plenti-TREK-1-GFP infection significantly increased TREK-1 expression in astrocytes compared with Plenti-sham-GFP infection cells (P < 0.05), and TREK-1 overexpression exhibited similar effects to the isoflurane dependent changes in the expression of BDNF, Bax and caspase-3, as TREK-1 overexpression reduced the expression of BDNF, and increased the expression of Bax and caspase-3, which was also observed for isoflurane treatment in XREF_FIG."
28944872
Progesterone affects KCNK2
| 6
Progesterone activates KCNK2.
| 5
Progesterone activates KCNK2. 5 / 5
| 5
reach
"Importantly, in uterine strips treated simultaneously with progesterone and L-methionine, no significant reduction in uterine contraction was observed, and the uterine contraction was at levels similar to those in control tissues without progesterone or L-methionine treatment, suggesting opposing effects of L-methionine and progesterone on TREK-1 channel mediated uterine relaxation TREK-1 activator arachidonic acid causes no further effect on progesterone induced uterine relaxation."
29416642
reach
"No statistical difference in oxytocin contraction was observed in tissues treated with progesterone plus arachidonic acid compared with the uterine strips treated with arachidonic acid alone or progesterone alone, suggesting that both arachidonic acid and progesterone activate TREK-1 mediated uterine relaxation to a similar extent Uterine stretch causes no further effect on progesterone induced uterine relaxation."
29416642
reach
"To determine whether the progesterone induced changes in uterine contraction are related TREK-1 activity, we tested the effects of TREK-1 inhibitor L-methionine (1 mM)."
29416642
reach
"The low levels of TREK-1 in proliferative phase endometrium, led us to examine whether progesterone might be driving TREK-1 down-regulation given its critical role in secretory endometrium."
23305490
reach
"The protein amount of TREK-1 was significantly enhanced in uterine strips treated with progesterone compared with control non treated uterine strips."
29416642
Progesterone decreases the amount of KCNK2.
| 1
Progesterone decreases the amount of KCNK2. 1 / 1
| 1
reach
"Our finding that progesterone did not lead to reduced TREK-1 expression implies additional regulatory mechanisms governing molecular expression of this channel."
23305490
Halothane affects KCNK2
| 2 6
Halothane activates KCNK2.
| 2 5
Halothane activates KCNK2. 5 / 5
| 2 5
reach
"XREF_BIBR examined TASK and TREK-1, and found that TREK-1 was activated by chloroform, diethyl ether, halothane and isoflurane, while TASK was activated by halothane and isoflurane."
20735416
reach
"As previously reported, arachidonic acid (20 microM) stimulated all of these channels, and a volatile anesthetic, halothane (1 mM) augmented TREK-1 and TREK-2 but not TRAAK."
16075240
reach
"Halothane activation of the related K2P channels TREK1 and TASK1 could be abolished by mutating a 6 amino acid motif located in the C-terminal domain (Talley and Bayliss, 2002), suggesting that halothane interacts directly with the channels."
21855646
reach
"Chloroform, diethyl ether, halothane and isoflurane activated TREK-1, whereas only halothane and isoflurane activated TASK."
10321245
reach
"XREF_BIBR expressed TREK-1 channels on HEK-293 cells and showed that TREK-1 currents were enhanced by nitrous oxide, xenon, cyclopropane and halothane."
20735416
Halothane inhibits KCNK2.
| 1
Halothane inhibits KCNK2. 1 / 1
| 1
reach
"They can be grouped according to sequence homology and functional similarities into several subfamilies, including : the halothane inhibited THIK-1 channel and related nonfunctional THIK-2; arachidonic acid and mechanosensitive TREK channels (TREK-1, TREK-2 and TRAAK); the weakly inwardly rectifying TWIK channels (TWIK-1, TWIK-2) and the nonfunctional KCNK7; and the acid sensitive TASK channels (TASK-1, TASK-2, TASK-3)."
11738652
SORT1 affects KCNK2
| 2 4
SORT1 binds KCNK2.
| 2 3
SORT1 binds KCNK2. 5 / 5
| 2 3
sparser
"Interestingly, sortilin physically interacts with the two pore domain potassium channel TREK-1 and the PE as well as its synthetic analog spadin is able to block the activation of TREK-1 highlighting their role in the depression pathology."
30670975
reach
"This interaction between TREK-1 and NTSR3 and Sortilin led us to examine whether NT and/or the partial NTSR3 and Sortilin propeptide (i.e. spadin) were able to act on TREK-1 channel activity."
20405001
reach
"This would lead to the internalization of the TREK-1 and Sortilin complex in early endosome and subsequently to its degradation."
20405001
sparser
"The association of TREK-1 with the sorting protein sortilin prompted us to investigate the behavior of mice deleted from the gene encoding sortilin ( Sort1 −/− )."
30127743
reach
"In physiological conditions (XREF_FIG), TREK-1 and NTSR3 and Sortilin would associate in the TGN vesicle, where spadin is hydrolyzed by furin."
20405001
SORT1 inhibits KCNK2.
| 1
SORT1 bound to two pore domain potassium channel inhibits KCNK2. 1 / 1
| 1
reach
"Interestingly, sortilin physically interacts with the two pore domain potassium channel TREK-1 and the PE as well as its synthetic analog spadin is able to block the activation of TREK-1 highlighting their role in the depression pathology."
30670975
Popdc proteins affects KCNK2
| 6
Popdc proteins binds KCNK2.
| 3
KCNK2 binds Popdc proteins. 3 / 3
| 3
reach
"The two-pore channel TREK-1 interacts with all three Popdc proteins."
24646234
reach
"Popdc proteins interact with the two-pore channel TREK-1 and enhance its current."
24282731
reach
"Popdc proteins interact with TREK-1 and Cav3."
24646234
Popdc proteins activates KCNK2.
| 3
Popdc proteins activates KCNK2. 3 / 3
| 3
reach
"Importantly, the increase in TREK-1 conductivity is accompanied by an about 2-fold higher membrane localisation of TREK-1, suggesting that Popdc proteins modulate membrane trafficking of TREK-1."
26772438
reach
"It is therefore believed that Popdc proteins modulate TREK-1 trafficking."
24646234
reach
"It is therefore plausible that Popdc proteins modulate TREK-1 trafficking."
27500161
PPY affects KCNK2
| 6
PPY inhibits KCNK2.
| 3
PPY inhibits KCNK2. 3 / 3
| 3
reach
"For example, TWIK and TWIK related K + (TREK) demonstrate high sensitivity to acidic pH inside the cell while the activity of the TWIK related acid sensitive K + (TASK) is inhibited by weak changes in extracellular pH XREF_BIBR, XREF_BIBR, XREF_BIBR."
25490401
reach
"TREK-1 was inhibited by acidic pH o via a sensor, His126 XREF_BIBR."
26879043
reach
"I TREK-1, w-c of WT is largely suppressed by pH e 6.9, and the inhibition is slightly attenuated in K312A and E315A."
28988317
PPY activates KCNK2.
| 3
PPY activates KCNK2. 2 / 2
| 2
reach
"We, therefore, examined whether any of these mutations affect pHi gating, and found that four of these eight mutants caused a marked shift in the pH activation of TREK-1 (XREF_FIG)."
21822218
reach
"Intracellular acidification (pH 7.0) increased the basal amplitude of TREK-1 current and resulted in hyperpolarizaton."
21343252
PPY activates KCNK2-T167P. 1 / 1
| 1
reach
"TREK-1 is also activated by external alkalinization [XREF_BIBR], but we found that pH 9.0 failed to activate the TREK-1 T167P mutant (not shown)."
27228168
KCNK2 affects isoflurane
| 6
KCNK2 activates isoflurane.
| 5
KCNK2 activates isoflurane. 5 / 5
| 5
reach
"Furthermore, the mRNA and protein expression of TREK-1 increased significantly in the 1.0 MAC (P < 0.05) and 1.5 MAC (P < 0.01) isoflurane treated groups."
28944872
reach
"In our study, isoflurane significantly decreased NADH, furthermore, over-expression of TREK1 also significantly decreased NADH, which further indicated that isoflurane induced neuroprotection by up-regulation of TREK1."
27469140
reach
"The over-expression of TREK-1 contributed to isoflurane induced astrocytic cytotoxicity."
28870160
reach
"TREK-1 mediates isoflurane induced cytotoxicity in astrocytes."
28870160
reach
"TREK-1 pathway mediates isoflurane induced memory impairment in middle aged mice."
29042297
KCNK2 inhibits isoflurane.
| 1
KCNK2 inhibits isoflurane. 1 / 1
| 1
reach
"As demonstrated in XREF_FIG, Lv-shRNA-TREK-1 infection significantly decreased TREK-1 mRNA and protein expression (P < 0.05) in astrocytes compared with Lv-shRNA-sham cells, and inhibited the effect of 1.0 and 1.5 MAC isoflurane on the expression of TREK-1, BDNF, Bax and caspase-3 (P < 0.05)."
28944872
KCNK2 affects COPB2
| 6
COPB2 binds KCNK2. 6 / 6
| 6
reach
"Several in vitro and in vivo binding assays confirmed the protein protein interaction between TREK1 and beta-COP."
20362547
reach
"The competitive inhibition assay revealed that the interaction between Flag-beta-COP and GFP-TREK1 was reduced dramatically with the addition of TREK1-N."
20362547
reach
"In addition, we confirmed the interaction between TREK1 and beta-COP under native conditions in PC3 prostate cancer cell, which highly expressed TREK1 channels [19]."
20362547
reach
"To investigate the interaction between TREK1 and beta-COP in vivo, N-terminal tagged vectors expressing Flag tagged TREK1 (Flag-TREK1) and GFP tagged beta-COP (GFP-beta-COP) were co-transfected into HEK293T cells."
20362547
reach
"The protein protein interaction between TREK1 and beta-COP was confirmed using the yeast two-hybrid and GST pull-down assays."
20362547
reach
"The direct binding of beta-COP with TREK1 in vivo was strongly supported by Immunoprecipitation experiment with an anti-TREK1 antibody in PC3 cells and by the co-localization of RFP-beta-COP with GFP-TREK1 at the plasma membrane of COS-7 cells."
20362547
Morphine(1+) affects KCNK2
| 1 4
Morphine(1+) activates KCNK2. 5 / 5
| 1 4
reach
"The pain relieving actions of morphine may be linked to TREK1 channel activity since morphine, acting through mu receptors, has been shown to enhance TREK1 current directly, and TREK1 knockout mice showed significantly less morphine induced analgesia than wild-type animals (Devilliers et al., 2013)."
29150838
reach
"Furthermore, more recent work has shown that morphine, acting through mu opioid receptors, enhances TREK-1 current directly."
26914156
sparser
"Of particular interest for a role in nociceptors is TREK1, based on the striking finding that TREK1 can be activated by morphine via mu opioid receptors, with analgesic action of morphine in TREK1 knockout animals being reduced by about half xref ."
28596533
reach
"Of particular interest for a role in nociceptors is TREK1, based on the striking finding that TREK1 can be activated by morphine via mu opioid receptors, with analgesic action of morphine in TREK1 knockout animals being reduced by about half 222."
28596533
reach
"Activation of TREK-1 by morphine results in analgesia without adverse side effects."
24346231
Copper(2+) affects KCNK2
| 1 2 3
Copper(2+) activates KCNK2. 5 / 5
| 1 2 3
reach
"In this study, we show that the two-pore-domain potassium channels TREK-1 and TASK-3 are potently modulated by both copper and zinc."
15322244
sparser
"It was shown that copper activated TREK-1 while an inhibition was seen with TASK-3 xref ."
25490401
reach
"Using site directed mutagenesis, we show that Asp128 plays a critical role in the copper activation of TREK-1."
15322244
sparser
"Using site-directed mutagenesis, we show that Asp128 plays a critical role in the copper activation of TREK-1."
15322244
reach
"It was shown that copper activated TREK-1 while an inhibition was seen with TASK-3 XREF_BIBR."
25490401
KCNK2 affects potassium(1+)
| 5
KCNK2 activates potassium(1+).
| 4
KCNK2 activates potassium(1+). 4 / 4
| 4
reach
"Fluoxetine, a commonly used antidepressant, was reported to block the currents of several potassium channels, which are mediated by Kv1.1, Kv1.3, Kv1.4, Kv1.5, Kv3.1, Kv4.3, hERG and TREK-1 XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
26579425
reach
"l-Lactate-induced TREK1 upregulation is a novel finding of physiological significance as TREK1 channels contribute to neuroprotection by enhancing potassium buffering and glutamate clearance capacity of astrocytes."
27062641
reach
"TREK-1 may modulate potassium current of glomus cells and/or afferent nerve endings in the rat carotid body."
16344329
reach
"Initially the inhibition of the TREK 1 channel causes dissociation of the C-terminal domain from the cell membrane and prevents the passage of potassium ions."
28928667
KCNK2 inhibits potassium(1+).
| 1
KCNK2 inhibits potassium(1+). 1 / 1
| 1
reach
"Electrophysiological research has shown that SID1900 and the previously reported TREK1 blocker (spadin) efficiently blocked TREK-1 current in HEK293 cells and specifically blocked two-pore domain potassium channels in primary cultured rat hippocampal neurons."
26441141
KCNK2 affects p38
| 5
KCNK2 phosphorylates p38.
| 2
Modified KCNK2 leads to the phosphorylation of p38 on Y182. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
Modified KCNK2 leads to the phosphorylation of p38 on T180. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
KCNK2 dephosphorylates p38.
| 2
Modified KCNK2 leads to the dephosphorylation of p38 on T180. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
Modified KCNK2 leads to the dephosphorylation of p38 on Y182. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
KCNK2 activates p38.
| 1
KCNK2 activates p38. 1 / 1
| 1
reach
"TREK-1 overexpression suppresses CHO cell proliferation by inhibiting the activity of PKA and p38 and MAPK signaling pathways and subsequently inducing G1 phase cell arrest."
27397543
KCNK2 affects SORT1
| 2 3
SORT1 binds KCNK2. 5 / 5
| 2 3
sparser
"Interestingly, sortilin physically interacts with the two pore domain potassium channel TREK-1 and the PE as well as its synthetic analog spadin is able to block the activation of TREK-1 highlighting their role in the depression pathology."
30670975
reach
"This interaction between TREK-1 and NTSR3 and Sortilin led us to examine whether NT and/or the partial NTSR3 and Sortilin propeptide (i.e. spadin) were able to act on TREK-1 channel activity."
20405001
reach
"This would lead to the internalization of the TREK-1 and Sortilin complex in early endosome and subsequently to its degradation."
20405001
sparser
"The association of TREK-1 with the sorting protein sortilin prompted us to investigate the behavior of mice deleted from the gene encoding sortilin ( Sort1 −/− )."
30127743
reach
"In physiological conditions (XREF_FIG), TREK-1 and NTSR3 and Sortilin would associate in the TGN vesicle, where spadin is hydrolyzed by furin."
20405001
KCNK2 affects GNG4
| 4 1
GNG4 binds KCNK2. 5 / 5
| 4 1
sparser
"The interaction of TREK-1 N terminus with GNG4 was also confirmed by MBP pull-down assay ( Figure S5 C)."
23021213
reach
"We confirmed the interaction between full-length TREK-1 and GNG4 via coimmunoprecipitation by using the antibodies against hemagglutinin (HA) and green fluorescent protein (GFP) after heterologously expressing GFP-GNG4 and HA-TREK-1 in HEK293T cells."
23021213
sparser
"We confirmed the interaction between full-length TREK-1 and GNG4 via coimmunoprecipitation by using the antibodies against hemagglutinin (HA) and green fluorescent protein (GFP) after heterologously expressing GFP-GNG4 and HA-TREK-1 in HEK293T cells ( Figure 3 C)."
23021213
sparser
"To map out the region of GNG4 that interacts with TREK-1, we divided the GNG4 protein sequence (75 amino acids) into two segments, N (1–31)- and C (32–75)-terminal segments, and checked for protein-protein interaction with full-length TREK-1 by coimmunoprecipitation ( Figure 3 D)."
23021213
sparser
"A previous yeast two-hybrid screen suggested that N terminus of TREK-1 interacts with GNG4 (subtype 4 of G γ subunit) ( Kim et al., 2010 )."
23021213
KCNK2 affects BVES
| 5
KCNK2 binds BVES.
| 4
BVES binds KCNK2. 4 / 4
| 4
reach
"Indeed, our FRET analysis of Popdc1 and TREK-1 interaction support the concept of a rapid ligand mediated modulation of protein protein interactions [XREF_BIBR]."
24646234
reach
"XREF_BIBR Recently, an investigation of ion channels and electrogenic proteins in Xenopus oocytes demonstrated that TREK-1 functionally interacts with BVES and POPDC1."
30863095
reach
"This concept finds support from our analysis of the interaction of TREK-1 and Popdc1 in Xenopus oocytes."
24646234
reach
"Based on the interaction of POPDC1 and TREK-1, a bi-molecular Forster-resonance energy transfer (FRET) sensor was constructed."
29534001
KCNK2 increases the amount of BVES.
| 1
KCNK2 increases the amount of BVES. 1 / 1
| 1
reach
"Co-expression of both Popdc1 and TREK-1 results in a current, which is approximately 2-fold higher than without Popdc1 and probably is caused by an increased membrane presence of TREK-1."
27500161
KCNK2 affects BAX
| 5
KCNK2 increases the amount of BAX.
| 2
Modified KCNK2 increases the amount of BAX. 2 / 2
| 2
reach
"As demonstrated in XREF_FIG, Plenti-TREK-1-GFP infection significantly increased TREK-1 expression in astrocytes compared with Plenti-sham-GFP infection cells (P < 0.05), and TREK-1 overexpression exhibited similar effects to the isoflurane dependent changes in the expression of BDNF, Bax and caspase-3, as TREK-1 overexpression reduced the expression of BDNF, and increased the expression of Bax and caspase-3, which was also observed for isoflurane treatment in XREF_FIG."
28944872
reach
"However, TREK-1 overexpression in astrocytes significantly downregulated BDNF expression, and upregulated Bax and caspase-3 expression."
28944872
KCNK2 activates BAX.
| 2
KCNK2 activates BAX. 2 / 2
| 2
reach
"Overexpression of TREK-1 downregulates BDNF, and upregulates Bax and caspase-3."
28944872
reach
"Furthermore, overexpression of TREK-1 in astrocytes downregulated BDNF, and upregulated Bax and caspase-3, while TREK-1 shRNA effectively reversed the isoflurane dependent changes in BDNF, Bax and caspase-3 expression."
28944872
KCNK2 decreases the amount of BAX.
| 1
Modified KCNK2 decreases the amount of BAX. 1 / 1
| 1
reach
"As demonstrated in XREF_FIG, Plenti-TREK-1-GFP infection significantly increased TREK-1 expression in astrocytes compared with Plenti-sham-GFP infection cells (P < 0.05), and TREK-1 overexpression exhibited similar effects to the isoflurane dependent changes in the expression of BDNF, Bax and caspase-3, as TREK-1 overexpression reduced the expression of BDNF, and increased the expression of Bax and caspase-3, which was also observed for isoflurane treatment in XREF_FIG."
28944872
GNG4 affects KCNK2
| 4 1
GNG4 binds KCNK2. 5 / 5
| 4 1
sparser
"The interaction of TREK-1 N terminus with GNG4 was also confirmed by MBP pull-down assay ( Figure S5 C)."
23021213
reach
"We confirmed the interaction between full-length TREK-1 and GNG4 via coimmunoprecipitation by using the antibodies against hemagglutinin (HA) and green fluorescent protein (GFP) after heterologously expressing GFP-GNG4 and HA-TREK-1 in HEK293T cells."
23021213
sparser
"We confirmed the interaction between full-length TREK-1 and GNG4 via coimmunoprecipitation by using the antibodies against hemagglutinin (HA) and green fluorescent protein (GFP) after heterologously expressing GFP-GNG4 and HA-TREK-1 in HEK293T cells ( Figure 3 C)."
23021213
sparser
"To map out the region of GNG4 that interacts with TREK-1, we divided the GNG4 protein sequence (75 amino acids) into two segments, N (1–31)- and C (32–75)-terminal segments, and checked for protein-protein interaction with full-length TREK-1 by coimmunoprecipitation ( Figure 3 D)."
23021213
sparser
"A previous yeast two-hybrid screen suggested that N terminus of TREK-1 interacts with GNG4 (subtype 4 of G γ subunit) ( Kim et al., 2010 )."
23021213
AMPK affects KCNK2
| 1 4
AMPK inhibits KCNK2. 5 / 5
| 1 4
reach
"However, AMPK is known to contribute to hyperpolarizing shifts in the voltage dependence of Nav1.5, decreased amplitudes of BK Ca, TASK, and TREK channel currents, and decreased membrane expression of Kv7.1 and Kir2.1 channels [XREF_BIBR], all effects that would presumably enhance cellular activity."
23831352
reach
"XREF_BIBR Instead, they found that AMPK activation inhibited the activity of the two related channels TREK-1 and TREK-2."
23181165
reach
"To the extent that carotid body O (2) sensitivity is dependent on AMPK, our finding that TREK-1 and TREK-2 channels are inhibited by AMPK suggests that TREK channels may represent the AMPK inhibited background K (+) channels that mediate activation of glomus cells by hypoxia."
19840997
reach
"We found that TREK-1 and TREK-2 channels but not TASK-1 or TASK-3 channels are inhibited by AMPK."
19840997
sparser
"The effects of azide on TREK occlude subsequent channel inhibition by AMPK and are attenuated by expression of a dominant negative catalytic subunit of AMPK (dnAMPK), suggesting that metabolic stress modulates TREK channels by an AMPK mechanism."
19840997
AGT affects KCNK2
| 2 3
AGT inhibits KCNK2. 5 / 5
| 2 3
sparser
"Inhibition of TREK1 by AngII was found to be due to a rise in [Ca 2+ ] i rather than PIP2 depletion [ xref ]."
25476848
reach
"This leak-type K + channel, later identified as TREK-1 of the two-pore K + (K2P) channel family, was potently inhibited by ACTH and AngII, leading directly to membrane depolarization."
23858003
reach
"Bovine adrenocortical cells express bTREK-1 K (+) (bovine KCNK2) channels that are inhibited by ANG II through a Gq coupled receptor by separate Ca (2+) and ATP hydrolysis dependent signaling pathways."
21613605
sparser
"Both AngII and vasopressin strongly inhibited (~70–80%) TREK1 and depolarized the cells by ~30 mV [ xref ]."
25476848
reach
"Inhibition of TREK1 by AngII was found to be due to a rise in [Ca 2+] i rather than PIP2 depletion [XREF_BIBR]."
25476848
Sevoflurane affects KCNK2
| 2 4
Sevoflurane activates KCNK2.
| 1 3
Sevoflurane activates KCNK2. 3 / 3
| 1 3
reach
"Studies have shown that sevoflurane can activate TREK-1 pathway through an indirect pathway at the cellular level, thereby preventing cell damage caused by ischemia and hypoxia."
28966677
reach
"Sevoflurane preconditioning apparently activates TREK-1 in differentiated SH-SY5Y cells and rat brain, and leads to tolerance against ischaemia."
24154701
reach
"The intracellular signal transduction events after activation of TREK-1 by sevoflurane are still unclear."
24154701
Sevoflurane increases the amount of KCNK2.
| 1 1
Sevoflurane increases the amount of KCNK2. 1 / 1
| 1 1
reach
"Sevoflurane preconditioning increased expression of TREK-1."
24154701
Lithium chloride affects KCNK2
| 4
Lithium chloride activates KCNK2.
| 3
Lithium chloride activates KCNK2. 3 / 3
| 3
reach
"Lithium chloride (LiCl, 1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) increased TREK-1 currents by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 72 +/- 12%, respectively, whereas they had no effect on TREK-2 channel activity."
29156592
reach
"Application of LiCl (1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) significantly activated TREK-1 by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 42 +/- 12%, respectively (n = 5, p < 0.05, XREF_FIG a, c)."
29156592
reach
"The activation of TREK-1 by LiCl, gabapentin, valproate, and carbamazepine was reversible and dose dependent."
29156592
Lithium chloride increases the amount of KCNK2.
| 1
Lithium chloride increases the amount of KCNK2. 1 / 1
| 1
reach
"In addition, western blot analysis showed LiCl and carbamazepine slightly upregulated TREK-1 expression, but not TREK-2 in the HT-22 cells."
29156592
Lig4-4 affects KCNK2
| 4
Lig4-4 inhibits KCNK2. 4 / 4
| 4
reach
"According to these results, a possible speculation is that lig4-4 inhibited TREK-1 and reduced K + efflux, therefore, depressed the process of cell apoptosis and resulted in up-regulation of Bcl-2 and suppression of caspase-3 activation."
29438799
reach
"In conclusion, we demonstrated that lig4-4 selectively inhibited TREK-1 and protected brain from cerebral ischemic injury."
29438799
reach
"We find in the present study that lig4-4 can potently inhibit TREK-1 currents, enhance cell viability and reduces cell apoptosis in cultured neurons during OGD induced injury."
29438799
reach
"Although lig4-4 was more potent to block TREK-1 than block other channels, we could not exclude the neuroprotective roles of lig4-4 through other ion channels.Previous studies demonstrated a connection between the function of various ion channels and pathophysiological outcome after transient or permanent cerebral artery occlusion in animals [36]."
29438799
Fatty acid affects KCNK2
| 4
Fatty acid activates KCNK2. 4 / 4
| 4
sparser
"TREK1, TREK2, and TRAAK are activated by arachidonic acid (AA) and other polyunsaturated fatty acids, such as docosahexaenoic acid and linoleic acid [ xref xref xref xref xref ]."
27790056
sparser
"These results show that rTRAAK is an alkali-sensing K+ channel that shows synergistic activation with pressure, and that the mechanism of activation of rTRAAK and TREK by free fatty acids are different."
11374070
sparser
"Our data suggest that the opening of background K(+) channels, like TREK-1 and TRAAK, which are activated by arachidonic acid and other polyunsaturated fatty acids such as docosahexaenoic acid and linolenic acid, is a significant factor in this neuroprotective effect."
10775263
sparser
"Activation of TREK-1 by polyunsaturated fatty acids."
22022421
Ethanol affects KCNK2
| 1 3
Ethanol inhibits KCNK2.
| 1 2
Ethanol inhibits KCNK2. 2 / 2
| 2
reach
"Alcohol inhibits TREK-1 in a PLD2 dependent manner [XREF_BIBR], but whether the metabolite can directly antagonize the channel has not been tested."
30529033
reach
"Using the cutoff determined with PLD2 as a prediction for TREK-1 inhibition and using whole cell patch clamp as a measurement, we found that octanol (8 carbons) and ethanol robustly inhibit TREK-1 currents in HEK293 cells expressing TREK-1 channels (XREF_FIG and XREF_SUPPLEMENTARY)."
30529033
Ethanol inhibits KCNK2. 1 / 1
| 1
sparser
"Alcohol inhibits TREK-1 in a PLD2 dependent manner[ xref ], but whether the metabolite can directly antagonize the channel has not been tested."
30529033
Ethanol binds KCNK2.
| 1
Ethanol binds KCNK2. 1 / 1
| 1
reach
"To further confirm that ethanol is not an allosteric antagonist, we tested ethanol binding to TREK-1 and TRAAK in our lipid binding assay [XREF_BIBR]."
30529033
Carbamazepine affects KCNK2
| 4
Carbamazepine activates KCNK2.
| 3
Carbamazepine activates KCNK2. 3 / 3
| 3
reach
"Application of LiCl (1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) significantly activated TREK-1 by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 42 +/- 12%, respectively (n = 5, p < 0.05, XREF_FIG a, c)."
29156592
reach
"As shown in XREF_FIG d, carbamazepine activated TREK-1 current in a dose dependent manner."
29156592
reach
"Lithium chloride (LiCl, 1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) increased TREK-1 currents by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 72 +/- 12%, respectively, whereas they had no effect on TREK-2 channel activity."
29156592
Carbamazepine increases the amount of KCNK2.
| 1
Carbamazepine increases the amount of KCNK2. 1 / 1
| 1
reach
"In addition, western blot analysis showed LiCl and carbamazepine slightly upregulated TREK-1 expression, but not TREK-2 in the HT-22 cells."
29156592
Spadin affects KCNK2
| 4
Spadin binds KCNK2.
| 3
KCNK2 binds Spadin. 3 / 3
| 3
reach
"Spadin binds specifically to TREK-1 with an affinity of 10 nM."
20405001
reach
"Spadin binds specifically to TREK-1 promoting its internalization [XREF_BIBR - XREF_BIBR]."
29928032
reach
"Spadin bound specifically to TREK-1 with an affinity of 10 nM."
20405001
Spadin inhibits KCNK2.
| 1
Spadin inhibits KCNK2. 1 / 1
| 1
reach
"Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels."
32317978
PKC affects KCNK2
| 1 3
PKC inhibits KCNK2. 4 / 4
| 1 3
reach
"Direct activation of protein kinase C (PKC) reduced the TREK-1 current, whereas PKC inhibition attenuated the AVP mediated reduction of the TREK-1 current, implicating the involvement of PKC."
26248219
sparser
"In a similar (if less robust) manner, KCNK2 is moderately inhibited by protein kinase C and A ( Fink et al., 1996 ) and activated by arachidonic acid, mechanical stretch, or lowered intracellular pH ( Patel et al., 1998, 1999; Maingret et al., 1999 ); KCNK3 is suppressed by lowered external pH ( Duprat et al., 1997; Kim et al., 1998; Leonoudakis et al., 1998; Lopes et al., 1998; Manjunath et al., 1999 ) in a potassium-dependent fashion ( Lopes et al., 2000 ) and down-regulated in motoneurons by neurotransmitters ( Talley et al., 2000 ); KCNK4 is moderately increased by unsaturated fatty acids and membrane stretch ( Fink et al., 1998; Maingret et al., 1999 ), and KCNK5 is inhibited by external acidification ( Reyes et al., 1998 )."
11159398
reach
"In other vascular preparations it was shown that acetylcholine binds to and activates muscarinic receptors in endothelial cells and TREK-1 is inhibited by PKC phosphorylation."
24086441
reach
"TREK-1 activation, unlike TRAAK, is reversed by protein kinase A and protein kinase C stimulation [18,19 **,20,24 **,27,30 **]."
11454447
PCSK7 affects KCNK2
| 2 2
PCSK7 activates KCNK2. 4 / 4
| 2 2
sparser
"As expected xref we observed activation of TREK1 by LPC or convex membrane curvature induced by negative pressure applied to cell-attached patches; however, although expression of TRPC5 conferred greater current in response to negative pressure, the current lacked the hallmark I – V of TRPC5 xref ."
19324410
sparser
"Additional TREK-1 activation in neurons by LIN or LPC would provide further protection [ xref ]."
18823665
reach
"As expected XREF_BIBR we observed activation of TREK1 by LPC or convex membrane curvature induced by negative pressure applied to cell attached patches; however, although expression of TRPC5 conferred greater current in response to negative pressure, the current lacked the hallmark I-V of TRPC5 XREF_BIBR."
19324410
reach
"Consistent with this perspective, the LPC activated TREK1 channel is activated by general anaesthetics XREF_BIBR."
19324410
ML67-33 affects KCNK2
| 4
ML67-33 activates KCNK2. 4 / 4
| 4
reach
"Finally, both BL-1249 and ML67-33 are known to activate TREK channels and they induce a current very similar to that induced by riluzole in nodose neurons [XREF_BIBR, XREF_BIBR]."
29928032
reach
"ML67-33 Activates the K 2P 2.1 (TREK-1) C-Type Gate."
23738709
reach
"The dihydroacridine analogue (ML67-33) has been found to selectively and directly activate TREK1, TREK2 and TRAAK channels (Bagriantsev et al., 2013)."
29150838
reach
"Importantly, ML67-33 strongly activates the three members of the TREK subfamily but not TASK-1, TASK-2, TASK-3 or TRESK [XREF_BIBR]."
29928032
KCNK2 affects arachidonic acid
| 4
KCNK2 activates arachidonic acid.
| 2
KCNK2 activates arachidonic acid. 2 / 2
| 2
reach
"Importantly, in uterine strips treated simultaneously with progesterone and L-methionine, no significant reduction in uterine contraction was observed, and the uterine contraction was at levels similar to those in control tissues without progesterone or L-methionine treatment, suggesting opposing effects of L-methionine and progesterone on TREK-1 channel mediated uterine relaxation TREK-1 activator arachidonic acid causes no further effect on progesterone induced uterine relaxation."
29416642
reach
"The present study showed that treatment of uterine strips with TREK-1 channel inhibitor L-methionine insignificantly increased uterine contraction, while treatment with TREK-1 activator arachidonic acid caused a dramatic reduction in uterine contraction, suggesting that the TREK-1 is active and functional during pregnancy in rats."
29416642
KCNK2 inhibits arachidonic acid.
| 1
KCNK2 inhibits arachidonic acid. 1 / 1
| 1
reach
"TREK-1 inhibitor L-methionine partly reversed uterine relaxation caused by the progesterone, while TREK-1 activator arachidonic acid did not cause significant change in progesterone induced relaxation."
29416642
KCNK2 binds arachidonic acid.
| 1
Arachidonic acid binds KCNK2. 1 / 1
| 1
reach
"We tested for direct binding of AA to TREK-1 and found both omega-3 and omega-6 AA (free fatty acid) competed with FL-PIP 2 (XREF_FIG)."
28793254
KCNK2 affects actin-
| 4
KCNK2 activates actin-. 4 / 4
| 4
reach
"A previous study reported that TREK-1 channels and ezrin are co-localized and that the expression of TREK-1 induces the formation of actin- and ezrin rich membrane protrusions."
28085542
reach
"Here, we show that the expression of TREK-1 markedly alters the cytoskeletal network and induces the formation of actin- and ezrin rich membrane protrusions."
15976821
reach
"In neurons for example, TREK-1 protein expression can induce the formation of actin- and ezrin rich membrane protrusions [XREF_BIBR], and deficiency of TREK-1 resulted in a decrease in the F-actin content of these cells [XREF_BIBR]."
26001192
reach
"reported that TREK-1 channels and ezrin are co-localized and also that the expression of TREK-1 induces the formation of actin- and ezrin rich membrane protrusions."
28085542
KCNK2 affects NADH
| 4
KCNK2 inhibits NADH. 4 / 4
| 4
reach
"Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH."
27469140
reach
"In our study, isoflurane significantly decreased NADH, furthermore, over-expression of TREK1 also significantly decreased NADH, which further indicated that isoflurane induced neuroprotection by up-regulation of TREK1."
27469140
reach
"The over-expression of TREK1 could decrease apoptosis and NADH in neurons."
27469140
reach
"As shown in XREF_FIG, over-expression of TREK1 reduced NADH significantly (p < 0.05)."
27469140
KCNK2 affects MAC
| 4
KCNK2 inhibits MAC.
| 3
KCNK2 inhibits MAC. 3 / 3
| 3
reach
"As demonstrated in XREF_FIG, Lv-shRNA-TREK-1 infection significantly decreased TREK-1 mRNA and protein expression (P < 0.05) in astrocytes compared with Lv-shRNA-sham cells, and inhibited the effect of 1.0 and 1.5 MAC isoflurane on the expression of TREK-1, BDNF, Bax and caspase-3 (P < 0.05)."
28944872
reach
"For example, although knockout of the TREK1 potassium channel increases the MAC of chloroform, desflurane, halothane, and sevoflurane, XREF_BIBR the increase is usually small and, more importantly, it is inconsistent, varying from 7% (desflurane) to 48% (halothane), and these changes do not correlate with the in vitro effects of these anesthetics on the TREK1 potassium channel."
18713900
reach
"Knockout of the TREK-1 potassium channel increases the MAC of chloroform, desflurane, halothane and sevoflurane."
18713892
KCNK2 activates MAC.
| 1
KCNK2 activates MAC. 1 / 1
| 1
reach
"Furthermore, the mRNA and protein expression of TREK-1 increased significantly in the 1.0 MAC (P < 0.05) and 1.5 MAC (P < 0.01) isoflurane treated groups."
28944872
KCNK2 affects IL6
| 1 3
KCNK2 inhibits IL6.
| 3
KCNK2 inhibits IL6. 3 / 3
| 3
reach
"This study was designed to investigate the mechanisms by which Trek-1 decreases IL-6 secretion."
23275623
reach
"We found that Trek-1 deficiency decreased IL-6 secretion from mouse and human AECs at both transcriptional and translational levels."
23275623
reach
"We recently reported the expression of K2P channels in alveolar epithelial cells (AECs) and found that TNF-alpha stimulation of TREK-1 deficient AECs caused decreased IL-6 secretion but increased MCP-1 secretion in vitro [XREF_BIBR, XREF_BIBR]."
25126877
KCNK2 binds IL6.
| 1
CEL binds IL6, KCNK2, and CCL2. 1 / 1
| 1
sparser
"Interestingly, the decrease in BAL fluid IL-6 and MCP-1 levels was associated with increased cellular apoptosis in TREK-1 deficient mice exposed to HO+MV."
25126877
KCNK2 affects EZR
| 4
KCNK2 activates EZR. 4 / 4
| 4
reach
"In neurons for example, TREK-1 protein expression can induce the formation of actin- and ezrin rich membrane protrusions [XREF_BIBR], and deficiency of TREK-1 resulted in a decrease in the F-actin content of these cells [XREF_BIBR]."
26001192
reach
"A previous study reported that TREK-1 channels and ezrin are co-localized and that the expression of TREK-1 induces the formation of actin- and ezrin rich membrane protrusions."
28085542
reach
"Here, we show that the expression of TREK-1 markedly alters the cytoskeletal network and induces the formation of actin- and ezrin rich membrane protrusions."
15976821
reach
"reported that TREK-1 channels and ezrin are co-localized and also that the expression of TREK-1 induces the formation of actin- and ezrin rich membrane protrusions."
28085542
DCPIB affects KCNK2
| 4
DCPIB activates KCNK2.
| 3
DCPIB activates KCNK2. 3 / 3
| 3
reach
"DCPIB, a known specific and potent inhibitor of volume regulated anion channels (VRAC), has been reported to activate TREK1 and TREK2 in astrocytes and in vitro recently."
30935201
reach
"Recently DCPIB was found to activate TREK potassium channels in cultured astrocytes."
26837888
reach
"Even more peculiar, DCPIB was found to enhance the activity of the two-pore domain K + channels TREK-1 and TREK-2, in their native environment and after recombinant expression [XREF_BIBR]."
26620797
DCPIB inhibits KCNK2.
| 1
DCPIB inhibits KCNK2. 1 / 1
| 1
reach
"The inhibitor of volume regulated anion channels DCPIB activates TREK potassium channels in cultured astrocytes."
23072356
BVES affects KCNK2
| 4
BVES binds KCNK2. 4 / 4
| 4
reach
"Indeed, our FRET analysis of Popdc1 and TREK-1 interaction support the concept of a rapid ligand mediated modulation of protein protein interactions [XREF_BIBR]."
24646234
reach
"XREF_BIBR Recently, an investigation of ion channels and electrogenic proteins in Xenopus oocytes demonstrated that TREK-1 functionally interacts with BVES and POPDC1."
30863095
reach
"This concept finds support from our analysis of the interaction of TREK-1 and Popdc1 in Xenopus oocytes."
24646234
reach
"Based on the interaction of POPDC1 and TREK-1, a bi-molecular Forster-resonance energy transfer (FRET) sensor was constructed."
29534001
Xenon(0) affects KCNK2
| 3
Xenon(0) activates KCNK2. 3 / 3
| 3
reach
"XREF_BIBR expressed TREK-1 channels on HEK-293 cells and showed that TREK-1 currents were enhanced by nitrous oxide, xenon, cyclopropane and halothane."
20735416
reach
"TREK-1 is markedly activated by clinically relevant concentrations of nitrous oxide, xenon, and cyclopropane."
14742687
reach
"The two-pore domain potassium channel TREK-1 is activated by xenon [XREF_BIBR]."
20836899
Serotonin affects KCNK2
| 3
Serotonin increases the amount of KCNK2.
| 1
Serotonin increases the amount of KCNK2. 1 / 1
| 1
reach
"Fluoxetine, a serotonin reuptake inhibitor antidepressant that has been previously found to inhibit TREK-1 channels, robustly, could attenuate the upregulation of TREK-1 expression and the inhibition of NSC proliferation induced by dexamethasone."
21069514
Serotonin decreases the amount of KCNK2.
| 1
Modified serotonin decreases the amount of KCNK2. 1 / 1
| 1
reach
"Given that the short allele confers elevated synaptic serotonin [XREF_BIBR], and females have been shown to have reduced serotonin transporter function and elevated levels of serotonin [XREF_BIBR], these findings suggest that elevated serotonin levels may reduce cortical TREK1 expression."
21871532
Serotonin binds KCNK2.
| 1
Serotonin binds KCNK2. 1 / 1
| 1
reach
"This study examined associations between serotonin and TREK1 by evaluating how pharmacologically manipulated (via chronic fluoxetine administration) as well as genetically conferred (SLC6A4; 5-HTTLPR genotype), differences in serotonin transporter function are linked to cortical TREK1 protein expression in rhesus monkeys."
21871532
Phosphatidic acid affects KCNK2
| 1 2
Phosphatidic acid inhibits KCNK2.
| 1 1
Phosphatidic acid inhibits KCNK2. 1 / 1
| 1
sparser
"D-myo-inositol-1,4,5-triphosphate and phosphatidyl-4,5-inositol-biphosphate depletion are involved in TASK channel inhibition, whereas diacylglycerols and phosphatidic acids directly inhibit TREK channels."
14532113
Phosphatidic acid inhibits KCNK2. 1 / 1
| 1
reach
"We characterized indirect PA mediated inhibition of TREK-1 by monitoring lipid production in live whole cells using a fluorescent PLD2 product release assay and ion channel current using live whole-cell patch-clamp electrophysiology."
31124840
Phosphatidic acid activates KCNK2.
| 1
Phosphatidic acid activates KCNK2. 1 / 1
| 1
reach
"PA appears to activate TREK-1 as phospholipase D2 (PLD2) directly binds to TREK-1 and activates the channel through local production of lipid."
28793254
Gamma-aminobutyric acid affects KCNK2
| 1 2
Gamma-aminobutyric acid activates KCNK2. 2 / 2
| 2
reach
"In the future, the genetic and optical control of native TREK1 afforded by the TREK1-PCS may allow the determination of the spatiotemporal properties and physiological significance of GABA B activation of TREK channels in the hippocampus."
23596388
reach
"Together, these results indicate that activation of hippocampal GABA B receptors activates not only Kir3 channels but also TREK1 channels, which are made light sensitive by the expression of the TREK1-PCS."
22726831
Gamma-aminobutyric acid activates KCNK2. 1 / 1
| 1
sparser
"In the future, the genetic and optical control of native TREK1 afforded by the TREK1-PCS may allow the determination of the spatiotemporal properties and physiological significance of GABA B activation of TREK channels in the hippocampus."
23596388
Flufenamic acid affects KCNK2
| 3
Flufenamic acid activates KCNK2.
| 2
Flufenamic acid activates KCNK2. 2 / 2
| 2
reach
"Fenamates, non steroid anti-inflammatory drugs, including BL-1249 and FFA (flufenamic acid) have been revealed to directly and reversibly activate TREK-1, TREK-2, and TRAAK channels but have also been reported to activate a number of other potassium channels."
29563879
reach
"Flufenamic acid (FA, 100 microM), niflumic acid (NA, 100 microM), and mefenamic acid (MA, 100 microM) markedly stimulated TREK-1, TREK-2, and TRAAK."
16075240
Flufenamic acid inhibits KCNK2.
| 1
Flufenamic acid inhibits KCNK2. 1 / 1
| 1
reach
"Fenamates, non steroid anti-inflammatory drugs, including BL-1249 and FFA (flufenamic acid) have been revealed to directly and reversibly activate TREK-1, TREK-2, and TRAAK channels but have also been reported to activate a number of other potassium channels."
29563879
Diltiazem affects KCNK2
| 3
Diltiazem inhibits KCNK2.
| 2
Diltiazem inhibits KCNK2. 2 / 2
| 2
reach
"Otherwise, fenamates can markedly stimulate the TREK-1, TREK-2 and TRAAK and diltiazem (1 mM) inhibited TREK-1 and TREK-2, but not TRAAK."
17689202
reach
"Diltiazem (1 mM) inhibited TREK-1 and TREK-2, but not TRAAK."
16075240
Diltiazem activates KCNK2.
| 1
Diltiazem activates KCNK2. 1 / 1
| 1
reach
"In the present study, modulation of TREK-1, TREK-2, and TRAAK channels by fenamates and diltiazem was examined."
16075240
Cyclopropane affects KCNK2
| 3
Cyclopropane activates KCNK2. 3 / 3
| 3
reach
"XREF_BIBR expressed TREK-1 channels on HEK-293 cells and showed that TREK-1 currents were enhanced by nitrous oxide, xenon, cyclopropane and halothane."
20735416
reach
"TREK-1 is markedly activated by clinically relevant concentrations of nitrous oxide, xenon, and cyclopropane."
14742687
reach
"Gaseous anesthetics such as xenon, nitrous oxide and cyclopropane activate TREK-1 XREF_BIBR."
22022421
TREK1-PCS affects KCNK2
| 3
TREK1-PCS binds KCNK2.
| 2
KCNK2 binds TREK1-PCS. 2 / 2
| 2
reach
"Furthermore, TREK1-PCS transfection in native tissue allowed the replacement of the WT and TREK1 dimer by the TREK1-PCS and WT-TREK 1 heterodimer."
23596388
reach
"Importantly, the TREK1-PCS and WT-TREK 1 heterodimer maintained wild-type internal and external regulation and rectification properties."
23596388
TREK1-PCS activates KCNK2.
| 1
TREK1-PCS activates KCNK2. 1 / 1
| 1
reach
"Furthermore, TREK1-PCS transfection in native tissue allowed the replacement of the WT and TREK1 dimer by the TREK1-PCS and WT-TREK 1 heterodimer."
23596388
TNF affects KCNK2
| 3
TNF activates KCNK2.
| 2
TNF activates KCNK2. 2 / 2
| 2
reach
"Although activation of several TNF-alpha induced signaling pathways, including p38 kinase and the PKCtheta isoform, appeared altered in TREK-1 deficient epithelial cells, the specific regulatory mechanisms underlying these signaling changes remains unclear."
25126877
reach
"We recently reported the expression of K2P channels in alveolar epithelial cells (AECs) and found that TNF-alpha stimulation of TREK-1 deficient AECs caused decreased IL-6 secretion but increased MCP-1 secretion in vitro [XREF_BIBR, XREF_BIBR]."
25126877
TNF binds KCNK2.
| 1
TNF binds KCNK2. 1 / 1
| 1
reach
"This binding was selective since NT was unable to displace the binding of 125 I-spadin and the N-terminal fragment Gln1-Arg16 bound to TREK-1 with a very low affinity (1 microM) close to that reported with NTSR3 and sortilin (XREF_FIG) XREF_BIBR."
20405001
SEPSECS affects KCNK2
| 2 1
SEPSECS activates KCNK2. 3 / 3
| 2 1
sparser
"The data obtained with TREK and TRAAK channel activation by LP are in favor the cone shape hypothesis [30••] ."
11454447
reach
"LP and PUFA activation of TREK and TRAAK channels thus clearly involves different mechanisms."
11454447
sparser
"LP and PUFA activation of TREK and TRAAK channels thus clearly involves different mechanisms."
11454447
PCS/WT affects KCNK2
| 3
KCNK2 binds PCS/WT. 3 / 3
| 3
reach
"This inhibition of the photo gated current in the TREK1 and PCS/WT heterodimer was 53.6 +/- 8% (n = 8), similar to the 60.6 +/- 5% (n = 8) inhibition of total current in WT alone (p> 0.7, t-test)."
22726831
reach
"We therefore tested the ability of the Gi coupled GABA B receptor (GABA B R) to regulate the light gated current of the TREK1 and PCS/WT heterodimer."
22726831
reach
"We next investigated the regulation of the TREK1 and PCS/WT heterodimer channel by internal modification induced by GPCR activation."
22726831
LPA affects KCNK2
| 3
LPA inhibits KCNK2. 3 / 3
| 3
reach
"In neurons from knockout animals LPA only activated depolarising currents (e.g. TRPV1, TRPA1) or slightly reduced hyperpolarising currents (TREK-1 or TASK-1) leading to enhanced excitability."
26224542
reach
"However, signalling by LPA receptors may also lead to inhibition of K2P channels as TREK-1 currents were inhibited by LPA when recombinantly expressed in Xenopus oocytes XREF_BIBR."
26224542
reach
"Most probably the inverse effect in TRESK [ko] DRG neurons resulted from TREK-1 and TASK-1 K2P channels, which also contribute to IK SO in DRG XREF_BIBR and were found to be inhibited by LPA XREF_BIBR."
26224542
KCNK2 affects halothane
| 3
KCNK2 inhibits halothane. 3 / 3
| 3
reach
"Deletion of TREK-1 significantly reduced the potency of halothane inhibition of 4-aminopyridine-evoked release of both glutamate and GABA without affecting control evoked release or the selective inhibition of glutamate vs GABA release."
17828284
reach
"Westphalen and colleagues 40 found that deletion of TREK-1 significantly reduced the inhibitory effect of halothane on glutamate release from cerebrocortical nerve terminals, which implies that reduced excitatory transmission is a possible mechanism of neuroprotective effect of anaesthetic preconditioning."
24154701
reach
"TREK-1 deletion also reduced halothane inhibition of basal glutamate release, but did not affect basal GABA release."
17828284
KCNK2 affects cell quiescence
| 3
KCNK2 activates cell quiescence.
| 2
KCNK2 activates cell quiescence. 2 / 2
| 2
reach
"The elevated expression seen in pregnant term samples when compared to laboring term samples revealed a dramatic decrease in gene expression consistent with the notion that TREK-1 contributes to myometrial quiescence at term (XREF_FIG)."
20811500
reach
"The stretch activated two pore potassium channel TREK-1 is up-regulated during gestation to term such that it may maintain uterine quiescence by hyperpolarizing the smooth muscle cell membrane."
22811574
KCNK2 inhibits cell quiescence.
| 1
KCNK2 inhibits cell quiescence. 1 / 1
| 1
reach
"Decreased expression of TREK-1 near term suggests that TREK-1 may contribute to uterine quiescence during gestation."
26400398
KCNK2 affects calcium(2+)
| 3
KCNK2 inhibits calcium(2+).
| 2
KCNK2 inhibits calcium(2+). 2 / 2
| 2
reach
"TASK2 and TREK1 blockade led to a decreased K + outward current and a decrease of ACh dependent Ca 2+ influx in C2C12 cells as potential underlying mechanisms."
27488672
reach
"Inhibition of TREK-1 by SPA induced a decrease of the resting membrane potential (DeltaV m ~ 12mV) and increased the cytosolic calcium concentration."
28105440
KCNK2 activates calcium(2+).
| 1
KCNK2 activates calcium(2+). 1 / 1
| 1
reach
"We hypothesize that TREK-1 depolarization is not enough to induce a robust calcium entry."
28105440
KCNK2 affects Spadin
| 3
KCNK2 binds Spadin. 3 / 3
| 3
reach
"Spadin binds specifically to TREK-1 with an affinity of 10 nM."
20405001
reach
"Spadin binds specifically to TREK-1 promoting its internalization [XREF_BIBR - XREF_BIBR]."
29928032
reach
"Spadin bound specifically to TREK-1 with an affinity of 10 nM."
20405001
KCNK2 affects Popdc proteins
| 3
KCNK2 binds Popdc proteins. 3 / 3
| 3
reach
"The two-pore channel TREK-1 interacts with all three Popdc proteins."
24646234
reach
"Popdc proteins interact with the two-pore channel TREK-1 and enhance its current."
24282731
reach
"Popdc proteins interact with TREK-1 and Cav3."
24646234
KCNK2 affects PPY
| 3
KCNK2 activates PPY.
| 2
KCNK2 activates PPY. 2 / 2
| 2
reach
"We found that mutations in the K 2P 2.1 (TREK-1) extracellular loops and at the Trp275 M4 position reduce the inhibitory effect of low pH O on channel activity."
21765396
reach
"In the I.O. patch configuration from h-TREK-1 and HEK clone, the TREK-1 current increased with the acidification from pH 7.2 to pH 5.2."
22022421
KCNK2 inhibits PPY.
| 1
KCNK2 inhibits PPY. 1 / 1
| 1
reach
"Activity of KCNK2 channels was moderately depressed by activators of PKC and PKA (Fink et al. 1996b) and increased by arachadonic acid, mechanical stretch, and lowered intracellular pH (Patel et al. 1998, Patel et al. 1999; Maingret et al. 1999)."
11055999
KCNK2 affects PLD2
| 2 1
KCNK2 binds PLD2. 2 / 2
| 2
sparser
"PA appears to activate TREK-1 as phospholipase D2 (PLD2) directly binds to TREK-1 and activates the channel through local production of lipid ( xref )."
28793254
sparser
"PA and PG are both products of the enzyme PLD2 ( xref ), and we expect these lipids to agonize the channel as PLD2 binds directly to the C terminus of TREK-1 and activates the channel ( xref ) (see also xref )."
28793254
KCNK2 binds PLD2 and phospholipase. 1 / 1
| 1
reach
"PA appears to activate TREK-1 as phospholipase D2 (PLD2) directly binds to TREK-1 and activates the channel through local production of lipid."
28793254
KCNK2 affects PCS/WT
| 3
KCNK2 binds PCS/WT. 3 / 3
| 3
reach
"This inhibition of the photo gated current in the TREK1 and PCS/WT heterodimer was 53.6 +/- 8% (n = 8), similar to the 60.6 +/- 5% (n = 8) inhibition of total current in WT alone (p> 0.7, t-test)."
22726831
reach
"We therefore tested the ability of the Gi coupled GABA B receptor (GABA B R) to regulate the light gated current of the TREK1 and PCS/WT heterodimer."
22726831
reach
"We next investigated the regulation of the TREK1 and PCS/WT heterodimer channel by internal modification induced by GPCR activation."
22726831
Gly-Gln affects KCNK2
| 3
Gly-Gln inhibits KCNK2. 3 / 3
| 3
reach
"Gq coupled receptor agonists inhibited TREK1 and TREK2 in heterologous expression system, and this effect was observed in bovine adrenal glomerulosa cells."
25476848
reach
"Stimulation of Gq coupled receptors was found to inhibit TREK activity by a mechanism involving protein kinase PKC and channel phosphorylation XREF_BIBR, XREF_BIBR, XREF_BIBR."
24086441
reach
"In addition, stimulation of Gq coupled receptors, including metabotropic mGluR1, and mGluR5 receptors, inhibits TREK-1 activity."
25374575
G betagamma affects KCNK2
| 3
G betagamma binds KCNK2.
| 2
KCNK2 binds G betagamma. 1 / 1
| 1
reach
"Finally, we tested whether TREK-1-mediated glutamate release requires direct binding of G betagamma to TREK-1 by utilizing the N-terminal segments of TREK-1 to compete for binding of G betagamma to TREK-1."
23021213
KCNK2 binds G betagamma and glutamate. 1 / 1
| 1
reach
"To answer the question, we considered a possibility that G betagamma directly binds to TREK-1 to open a glutamate permeable channel."
23021213
G betagamma activates KCNK2.
| 1
G betagamma activates KCNK2. 1 / 1
| 1
reach
"To determine whether activation of TREK-1 by G betagamma can release glutamate from astrocytes, we performed two-cell sniffer patch (Lee et al., 2010)."
23021213
BL-1249 affects KCNK2
| 3
BL-1249 activates KCNK2. 3 / 3
| 3
reach
"Finally, Tertyshnikova et al. used a similar approach to demonstrate that BL-1249 enhanced TREK-1 currents in human bladder cells [XREF_BIBR]."
29928032
reach
"Furthermore, spadin was unable to prevent activation of TREK-1 by BL-1249, CDC, or the related bioactive lipid, DHA."
32317978
reach
"Finally, both BL-1249 and ML67-33 are known to activate TREK channels and they induce a current very similar to that induced by riluzole in nodose neurons [XREF_BIBR, XREF_BIBR]."
29928032
BDNF affects KCNK2
| 1 2
BDNF binds KCNK2.
| 1 1
BDNF binds KCNK2. 2 / 2
| 1 1
sparser
"Taken together, the results of the present study indicate that isoflurane-induced cell damage in astrocytes may be associated with TREK-1-mediated inhibition of BDNF and provide a reference for the safe use of isoflurane anesthesia in infants and children."
28944872
reach
"To investigate the downstream mechanism responsible for the neuroprotective effects elicited by TREK-1 inhibition in isoflurane induced astrocytic cytotoxicity, we analysed the association between TREK-1 and BDNF."
28870160
BDNF activates KCNK2.
| 1
BDNF activates KCNK2. 1 / 1
| 1
reach
"Lentiviruses were used to overexpress or knockdown TREK-1 in astrocytes exposed to increasing concentrations of isoflurane or O 2 for 2 h. Subsequently, the mRNA and protein expression of brain derived neurotrophic factor (BDNF), caspase-3, Bcl-2-associated X (Bax) and TREK-1 was measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively."
28944872
Akap5 affects KCNK2, and Mtap2
| 3
KCNK2 binds Akap5 and Mtap2. 3 / 3
| 3
sparser
"TREK Channel Interactions with AKAP150 and Mtap2."
21358977
sparser
"Mtap2 and AKAP150 can bind to TREK-1 simultaneously and modulate the channel synergistically ( xref )."
26772438
sparser
"In particular, AKAP150 and Mtap2 interact simultaneously with the C-terminus of TREK1 and enhance cell-surface expression and activation of the channel [15] ."
20362547
ATP affects KCNK2
| 3
ATP activates KCNK2. 3 / 3
| 3
reach
"Here, in rat ventricular cardiomyocytes using the whole-cell patch-clamp technique, we characterize for the first time a native TREK-1-like current (I (TREK)) that is activated by ATP, a purine agonist applied at a micromolar range."
10993907
reach
"Trek like potassium channels in rat cardiac ventricular myocytes are activated by intracellular ATP."
11891578
reach
"We conclude that intracellular ATP directly activates TREK like channels, a property not previously described."
11891578
Zinc atom affects KCNK2
| 1 1
Zinc atom inhibits KCNK2.
| 1
Zinc atom inhibits KCNK2. 1 / 1
| 1
sparser
"Zinc inhibits the two-pore domain potassium TREK-1 and TASK-3 channels with IC 50 s of 659 and 12.7 µM, respectively [ xref ], while, zinc positively modulates TREK-2 with an EC 50 of 87.1 µM [ xref ]."
27384555
Zinc atom activates KCNK2.
| 1
Zinc atom activates KCNK2. 1 / 1
| 1
reach
"It is generally agreed that in expression systems Zn 2+ and Hg 2+ enhance the amplitude of TREK1 and TREK2 and strongly decrease the amplitude of the rodent TRESK and TASK3 currents."
24086441
Valproic acid affects KCNK2
| 2
Valproic acid activates KCNK2. 2 / 2
| 2
reach
"Lithium chloride (LiCl, 1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) increased TREK-1 currents by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 72 +/- 12%, respectively, whereas they had no effect on TREK-2 channel activity."
29156592
reach
"Application of LiCl (1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) significantly activated TREK-1 by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 42 +/- 12%, respectively (n = 5, p < 0.05, XREF_FIG a, c)."
29156592
Sodium(1+) affects KCNK2
| 1 2
Sodium(1+) activates KCNK2. 2 / 2
| 1 2
reach
"Sodium nitroprusside (10 (-6) or 10 (-5) m) and 8-Br-cGMP (10 (-4) or 10 (-3) m) increased TREK-1 currents in perforated whole cell and single channel recordings."
11560940
reach
"TREK-1 is " activated " by extracellular sodium (Fink etal, 1996), accordingly, replacing extracellular Na + by NMDG + strongly reduced wild-type TREK-1 outward currents (Fig XREF_FIG D)."
28242754
Pyraclofos affects KCNK2
| 2
Pyraclofos activates KCNK2. 2 / 2
| 2
reach
"Strikingly, replacement of intracellular K + by Rb + increased the voltage dependent activation of TREK-1 around 100-fold, resulting in large outward currents and large tail currents (XREF_FIG A)."
26919430
reach
"Furthermore, activation by PIP 2, intracellular pH and membrane stretch have been shown to abolish voltage activation in TREK-1, thus effectively causing a gating mode shift."
26919430
Prostaglandin F2alpha(1-) affects KCNK2
| 2
Prostaglandin F2alpha(1-) inhibits KCNK2. 1 / 1
| 1
reach
"One of the most potent bioactive lipid activators of TREK-2 was 11-deoxy prostaglandin F2alpha, which was found to activate TREK-2 and inhibit TREK-1."
27805811
Prostaglandin F2alpha(1-) activates KCNK2. 1 / 1
| 1
reach
"We first assessed whether 11-deoxy prostaglandin F2alpha also activated TREK-1 in the T-REx-TREK-1 Tl + assay."
27805811
Monoacylglycerol phosphate affects KCNK2
| 2
Monoacylglycerol phosphate activates KCNK2. 2 / 2
| 2
sparser
"TREK1 and TRAAK are also activated by lysophospholipids, including lysophosphatidylcholine and lysophosphatitylinositol [ xref xref ]."
27790056
sparser
"Polyunsaturated fatty acids (PUFAs) such as Arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) or lysophospholipids (LP) such as lysophosphatidylcholine (LPC) also activate TREK-1 channels and are neuroprotective against both ischemia and seizures induced by kainate injections xref , xref ."
22022421
Lactate affects KCNK2
| 2
Lactate activates KCNK2. 2 / 2
| 2
reach
"In the present study, we show that ischaemic concentrations of lactate (30mM) at pH 7.0 and 6.5, commonly observed during ischemia, cause robust potentiation of human TREK1 (hTREK1) activity at single-channel level in cell-free inside-out membrane patches, while 30mM lactate at pH 6.0 to 5.5, commonly observed during hyperglycaemic ischemia, reduces hTREK1 channel activity significantly."
26843094
reach
"Ischaemic concentrations of lactate increase TREK1 channel activity by interacting with a single histidine residue in the carboxy terminal domain."
26445100
Gabapentin affects KCNK2
| 2
Gabapentin activates KCNK2. 2 / 2
| 2
reach
"Application of LiCl (1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) significantly activated TREK-1 by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 42 +/- 12%, respectively (n = 5, p < 0.05, XREF_FIG a, c)."
29156592
reach
"Lithium chloride (LiCl, 1 mM), gabapentin (100 muM), valproate (100 muM), and carbamazepine (100 muM) increased TREK-1 currents by 31 +/- 14%, 25 +/- 11%, 28 +/- 12%, and 72 +/- 12%, respectively, whereas they had no effect on TREK-2 channel activity."
29156592
Escitalopram affects KCNK2
| 2
Escitalopram inhibits KCNK2.
| 1
Escitalopram inhibits KCNK2. 1 / 1
| 1
reach
"Escitalopram reversibly inhibited TREK-1 currents in a concentration dependent manner."
25675906
Escitalopram decreases the amount of KCNK2.
| 1
Escitalopram decreases the amount of KCNK2. 1 / 1
| 1
reach
"Escitalopram significantly reversed the regional increases of TREK-1 expression and the reduction of hippocampal NSC proliferation in PSD rats."
25675906
Dinitrogen oxide affects KCNK2
| 2
Dinitrogen oxide activates KCNK2. 2 / 2
| 2
reach
"XREF_BIBR expressed TREK-1 channels on HEK-293 cells and showed that TREK-1 currents were enhanced by nitrous oxide, xenon, cyclopropane and halothane."
20735416
reach
"TREK-1 is markedly activated by clinically relevant concentrations of nitrous oxide, xenon, and cyclopropane."
14742687
Curcumin affects KCNK2
| 1 2
Curcumin inhibits KCNK2.
| 1 1
Curcumin inhibits KCNK2. 1 / 1
| 1 1
reach
"The TREK-1 blocker curcumin reduced proliferation by 44% at 120 hrs at the highest concentration tested (XREF_FIG D), whereas L-methionine (XREF_FIG A) and L-methioninol, blockers of stretch dependent channels thought to be TREK-1, showed no effect (P> 0.05) on proliferation."
23305490
Curcumin activates KCNK2.
| 1
Curcumin activates KCNK2. 1 / 1
| 1
reach
"Evidence in favour of a contribution of TREK-1 in proliferative phase endometrium is corroborated by its higher expression during this period and our finding that the TREK-1 modulators curcumin and zinc modify cell proliferation."
23305490
Chlorpromazine affects KCNK2
| 2
Chlorpromazine inhibits KCNK2. 2 / 2
| 2
reach
"TREK channels are also inhibited by chlorpromazine, local anesthetics and the antidepressant fluoxetine."
17659475
reach
"Application of 10 muM fluoxetine, 20 muM paroxetine, 100 muM citalopram, and 30 muM chlorpromazine significantly inhibited TREK-1 currents by 28 +/- 11%, 40 +/- 9%, 31 +/- 10%, and 52 +/- 10%, respectively (p < 0.05, XREF_FIG a-c)."
29156592
Capsaicin affects KCNK2
| 2
Capsaicin increases the amount of KCNK2. 2 / 2
| 2
reach
"Also, TREK-1, which is most homology with TREK-2, involved in polymodal pain perception, is highly expressed in small sensory neurons and extensively colocalized with TRPV1, the capsaicin activated nonselective ion channel [31]."
17689202
reach
"TREK-1 is highly expressed in small sensory neurons, is present in both peptidergic and nonpeptidergic neurons and is extensively colocalized with TRPV1, the capsaicin activated nonselective ion channel."
16675954
Barium(2+) affects KCNK2
| 2
Barium(2+) inhibits KCNK2. 2 / 2
| 2
reach
"Ba (2+) slightly inhibited TREK currents but only at high concentrations."
15857947
reach
"Under basal conditions, both TREK-1 and TREK-2 currents were insensitive to application of spadin, but could be blocked by Ba 2+."
32317978
All-cis-docosa-4,7,10,13,16,19-hexaenoic acid affects KCNK2
| 1 1
All-cis-docosa-4,7,10,13,16,19-hexaenoic acid activates KCNK2. 2 / 2
| 1 1
sparser
"Polyunsaturated fatty acids (PUFAs) such as Arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) or lysophospholipids (LP) such as lysophosphatidylcholine (LPC) also activate TREK-1 channels and are neuroprotective against both ischemia and seizures induced by kainate injections xref , xref ."
22022421
reach
"Docosahexaenoic acid, linolenic acid and linoleic acid have been shown to directly stimulate two-pore domain potassium channel (TREK and TRAAK channels) which causes hyperpolarization and promotes vascular relaxation XREF_BIBR."
23409085
TREK-2 activators affects KCNK2
| 2
TREK-2 activators inhibits KCNK2. 2 / 2
| 2
reach
"Since some of the identified TREK-2 activators cause inhibition of TREK-1, we used chimeric TREK-2 and TREK-1 channels to identify potential regulatory domains responsible for this small molecule mode switching."
27805811
reach
"Future studies will determine whether the TREK-2 activators that inhibit TREK-1 can be chemically optimized into selective TREK channel inhibitors."
27805811
TREK-1 siRNA affects KCNK2
| 2
TREK-1 siRNA decreases the amount of KCNK2. 2 / 2
| 2
reach
"TREK-1 protein expression was down-regulated by TREK-1 siRNA [0.13 (0.03)], compared with control siRNA [0.89 (0.06); P < 0.05]."
24154701
reach
"TREK-1 siRNA given intracerebroventrically (siRNA group) reduced expression of TREK-1 as demonstrated by western blot [0.58 (0.04)-fold in the siRNA group, P < 0.05 vs control, Fig."
24154701
PUM3 affects KCNK2
| 1 1
PUM3 activates KCNK2. 2 / 2
| 1 1
sparser
"LP and PUFA activation of TREK and TRAAK channels thus clearly involves different mechanisms."
11454447
reach
"LP and PUFA activation of TREK and TRAAK channels thus clearly involves different mechanisms."
11454447
PRNP affects KCNK2
| 2
KCNK2 binds PRNP. 1 / 1
| 1
sparser
"Furthermore, a deletion mapping study defined the carboxyl-terminal regions of the two proteins as the possible determinants of the PrP(C)-TREK-1 interaction."
16750514
KCN binds KCNK2 and PRNP. 1 / 1
| 1
sparser
"Using a bacterial two-hybrid approach, we identified a novel interaction between PrP(C) and a two-pore potassium channel protein, TREK-1."
16750514
PE affects KCNK2
| 2
PE inhibits KCNK2. 2 / 2
| 2
reach
"Only, the PE 22-28 was able to efficiently block TREK-1 activity (55.46 +/- 4.6%, n = 13, p < 0.0001)."
28955242
reach
"Interestingly, we found that PE 12-27 was able to strongly inhibit TREK-1 activity (28.4 +/- 9.9%, n = 22, p = 0.03; Figures XREF_FIG)."
28955242
NTSR3 affects KCNK2
| 2
KCNK2 binds NTSR3. 2 / 2
| 2
reach
"In physiological conditions (XREF_FIG), TREK-1 and NTSR3 and Sortilin would associate in the TGN vesicle, where spadin is hydrolyzed by furin."
20405001
reach
"This interaction between TREK-1 and NTSR3 and Sortilin led us to examine whether NT and/or the partial NTSR3 and Sortilin propeptide (i.e. spadin) were able to act on TREK-1 channel activity."
20405001
Mir27a affects KCNK2
| 2
Mir27a activates KCNK2. 2 / 2
| 2
reach
"Mir27a is likely targeting the potassium channel the Kcnk2 gene."
26822703
reach
"It is likely that Mir27a is targeting Kcnk2."
26822703
MTDH affects KCNK2
| 2
Modified MTDH increases the amount of KCNK2. 1 / 1
| 1
reach
"Upregulation of AEG-1 increased expression of TREK-1 in astrocytes, and knockdown of AEG-1 dramatically decreased the mRNA and protein levels of TREK-1, which were restored by expression of shRNA-insensitive AEG-1."
31782179
MTDH increases the amount of KCNK2. 1 / 1
| 1
reach
"Upregulation of AEG-1 increased expression of TREK-1 in astrocytes, and knockdown of AEG-1 dramatically decreased the mRNA and protein levels of TREK-1, which were restored by expression of shRNA-insensitive AEG-1."
31782179
ML67 affects KCNK2
| 2
ML67 inhibits KCNK2.
| 1
ML67 inhibits KCNK2. 1 / 1
| 1
reach
"In contrast, ML67 reversibly activated K 2P 2.1 (TREK-1), increasing currents by up to ~ 11-fold (EC 50 213.0 +/- 1.2 muM, Figure XREF_FIG B, D, E and Table 1)."
23738709
ML67 activates KCNK2.
| 1
ML67 activates KCNK2. 1 / 1
| 1
reach
"In contrast, ML67 reversibly activated K 2P 2.1 (TREK-1), increasing currents by up to ~ 11-fold (EC 50 213.0 +/- 1.2 muM, Figure XREF_FIG B, D, E and Table 1)."
23738709
ML402 affects KCNK2
| 2
ML402 activates KCNK2. 2 / 2
| 2
reach
"ML335 and ML402 activate K 2P 2.1 (TREK-1) in HEK293 cells similar to their effects in Xenopus oocytes (5.2 +/- 0.8 muM and 5.9 +/- 1.6 muM for ML335 and ML402, respectively (n> = 3)) (XREF_FIG, XREF_FIG)."
28693035
reach
"Xenopus oocyte two electrode voltage-clamp measurements show that ML335 and ML402 activate K 2P 2.1 (TREK-1) and K 2P 10.1 (TREK-2) but not K 2P 4.1 (TRAAK) (14.3 +/- 2.7 muM, K 2P 2.1 (TREK-1) : ML335; 13.7 +/- 7.0 muM, K 2P 2.1 (TREK-1) : ML402; 5.2 +/- 0.5 muM, K 2P 10.1 (TREK-2) : ML335; and 5.9 +/- 1.6 muM, K 2P 10.1 (TREK-2) : ML402) (XREF_FIG, XREF_FIG)."
28693035
ML335 affects KCNK2
| 2
ML335 activates KCNK2. 2 / 2
| 2
reach
"ML335 and ML402 activate K 2P 2.1 (TREK-1) in HEK293 cells similar to their effects in Xenopus oocytes (5.2 +/- 0.8 muM and 5.9 +/- 1.6 muM for ML335 and ML402, respectively (n> = 3)) (XREF_FIG, XREF_FIG)."
28693035
reach
"Xenopus oocyte two electrode voltage-clamp measurements show that ML335 and ML402 activate K 2P 2.1 (TREK-1) and K 2P 10.1 (TREK-2) but not K 2P 4.1 (TRAAK) (14.3 +/- 2.7 muM, K 2P 2.1 (TREK-1) : ML335; 13.7 +/- 7.0 muM, K 2P 2.1 (TREK-1) : ML402; 5.2 +/- 0.5 muM, K 2P 10.1 (TREK-2) : ML335; and 5.9 +/- 1.6 muM, K 2P 10.1 (TREK-2) : ML402) (XREF_FIG, XREF_FIG)."
28693035
Lig4-4 affects KCNK2
| 2
Lig4-4 inhibits KCNK2. 2 / 2
| 2
reach
"Lig4-4 selectively inhibits TREK-1 and plays potent neuroprotective roles in vitro and in rat MCAO model."
29438799
reach
"Lig4-4 inhibited TREK-1 currents in a dose dependent manner."
29438799
LPI affects KCNK2
| 1 1
LPI activates KCNK2. 2 / 2
| 1 1
reach
"Similarly, it has been shown that LPI activates TREK channels such as bTREK-1 and bKv1.4 K + currents [XREF_BIBR]."
26784247
sparser
"Similarly, it has been shown that LPI activates TREK channels such as bTREK-1 and bKv1.4 K + currents [ xref ]."
26784247
L-prolylglycine affects KCNK2
| 2
L-prolylglycine activates KCNK2. 2 / 2
| 2
reach
"5-15 mol% PG dose-dependently activated TREK-1 in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes, as determined by potassium ion flux (XREF_FIG and XREF_FIG)."
28793254
reach
"Unexpectedly, sub-saturating PIP 2 (0.5 mol%) in the presence of 10 mol% PG enhanced TREK-1 activity (XREF_FIG and XREF_FIG)."
28793254
L-methionine affects KCNK2
| 2
L-methionine inhibits KCNK2.
| 1
L-methionine inhibits KCNK2. 1 / 1
| 1
reach
"The TREK-1 blocker l-methionine enhanced oxytocin contraction in Singleton-Term and twin pregnant uterus, and reversed the decreases in contraction in uterine strips exposed to prolonged stretch."
29577872
L-methionine activates KCNK2.
| 1
L-methionine activates KCNK2. 1 / 1
| 1
reach
"Blockade of stretch activated channels with a channel non specific tarantula toxin (GsMTx-4) or the more specific TREK-1 antagonist L-methionine ethyl ester altered contractile frequency in a dose dependent manner in pregnant myometrium."
20811500
KCNK2 affects spadin
| 2
KCNK2 binds spadin. 2 / 2
| 2
reach
"XREF_FIG shows that spadin bound specifically to TREK-1 with an affinity of about 10 nM."
20405001
reach
"Taken together, these results indicate that TREK-1 and NTSR3 and Sortilin are not only associated within the plasma membrane but that spadin interacts directly with TREK-1 to functionally inhibit its activity."
20405001
KCNK2 affects sodium atom
| 2
KCNK2 activates sodium atom. 1 / 1
| 1
reach
"TREK-1 is " activated " by extracellular sodium (Fink etal, 1996), accordingly, replacing extracellular Na + by NMDG + strongly reduced wild-type TREK-1 outward currents (Fig XREF_FIG D)."
28242754
KCNK2-I267T activates sodium atom. 1 / 1
| 1
reach
"Thus, mutant TREK-1 I267T channels might cause intracellular Na + overload and depolarization of cardiac cells, effects which could trigger arrhythmias via secondary Ca 2+ overload."
28242754
KCNK2 affects phenazine-1-carboxylate
| 2
KCNK2 activates phenazine-1-carboxylate. 2 / 2
| 2
reach
"Taken together, our results demonstrated that TREK-1 knockdown inhibited cell proliferation of PCa cells."
25962960
reach
"Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell cycle arrest."
25962960
KCNK2 affects miR-183-5p
| 2
KCNK2 inhibits miR-183-5p.
| 1
KCNK2 inhibits miR-183-5p. 1 / 1
| 1
reach
"In addition, over-expression of TREK-1 blocked the roles of miR-183-5p in neuropathic pain."
29736614
KCNK2 binds miR-183-5p.
| 1
KCNK2 binds miR-183-5p. 1 / 1
| 1
reach
"Luciferase assays confirmed the binding of miR-183-5p and TREK-1."
29736614
KCNK2 affects corticosterone
| 2
KCNK2 increases the amount of corticosterone. 2 / 2
| 2
reach
"Deletion of TREK-1 in mice caused a substantially reduced elevation of corticosterone levels under stress, and produced behaviour similar to that of naive animals treated with fluoxetine in various behavioural tests."
17703894
reach
"Deletion of TREK-1 in mice caused a substantially reduced elevation of corticosterone levels under stress, and produced behavior similar to that of naive animals treated with fluoxetine in various behavioral tests."
28682878
KCNK2 affects cell death
| 2
KCNK2 inhibits cell death. 2 / 2
| 2
reach
"The above effects were specific to l-lactate as pyruvate failed to increase TREK1 expression and reduce cell death."
27062641
reach
"TREK-1, the product of the kcnk2 gene, regulates cell excitability and prevents neuron death by inhibiting NMDA dependent glutamatergic excitotoxicity induced by ischemia."
26909044
KCNK2 affects cell cycle
| 2
KCNK2 inhibits cell cycle. 2 / 2
| 2
reach
"Our results showed that TREK-1 knockdown induced G1/S cell cycle arrest in PC-3 cells."
25962960
reach
"Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell cycle arrest."
25962960
KCNK2 affects TREK1-PCS
| 2
KCNK2 binds TREK1-PCS. 2 / 2
| 2
reach
"Furthermore, TREK1-PCS transfection in native tissue allowed the replacement of the WT and TREK1 dimer by the TREK1-PCS and WT-TREK 1 heterodimer."
23596388
reach
"Importantly, the TREK1-PCS and WT-TREK 1 heterodimer maintained wild-type internal and external regulation and rectification properties."
23596388
KCNK2 affects TKDC
| 2
KCNK2 binds TKDC. 2 / 2
| 2
reach
"In the S complex simulations, the interactions between TKDC and TREK-1 were stable."
28851868
reach
"A TREK-1 and TKDC complex simulation system (termed S complex) was built by inserting the docking model of TREK-1 and TKDC into an explicit membrane environment."
28851868
KCNK2 affects PRNP
| 2
KCNK2 binds PRNP. 1 / 1
| 1
sparser
"Furthermore, a deletion mapping study defined the carboxyl-terminal regions of the two proteins as the possible determinants of the PrP(C)-TREK-1 interaction."
16750514
KCN binds KCNK2 and PRNP. 1 / 1
| 1
sparser
"Using a bacterial two-hybrid approach, we identified a novel interaction between PrP(C) and a two-pore potassium channel protein, TREK-1."
16750514
KCNK2 affects PKC
| 2
KCNK2 leads to the dephosphorylation of PKC. 2 / 2
| 2
reach
"Additionally, both Trek1 and Trek2 channels are inhibited by protein kinase A (PKA) and protein kinase C (PKC) phosphorylation, which couples these channels to G s, G i/o, and G q G protein signaling cascades."
22973213
reach
"Trek channels are also inhibited by protein kinase A (PKA) and protein kinase C (PKC) phosphorylation, which couples channel activity to G protein dependent signaling cascades involving G s, G i/o, and G q G-proteins."
21821104
KCNK2 affects PKA
| 1 1
KCNK2 binds PKA.
| 1
PKA binds KCNK2. 1 / 1
| 1
sparser
"Previous studies have described an interaction between Popeye domain‐containing proteins (Popdc1 and Popdc2) and TREK‐1 that is important for its regulation by protein kinase A, with implications for pacemaking in the mouse. xref Similarly, even earlier work identified an association between TREK‐1 and A kinase anchor protein 150 that controls response of channel to Gs‐coupled receptor activation. xref Our new findings together with our previous work xref indicate that β IV ‐spectrin associates with TREK‐1 and is essential for its proper membrane targeting in myocytes throughout the heart."
27098968
KCNK2 activates PKA.
| 1
KCNK2 activates PKA. 1 / 1
| 1
reach
"TREK-1 overexpression suppresses CHO cell proliferation by inhibiting the activity of PKA and p38 and MAPK signaling pathways and subsequently inducing G1 phase cell arrest."
27397543
KCNK2 affects PDLIM4
| 2
KCNK2 activates PDLIM4. 2 / 2
| 2
reach
"It is more difficult to discern which TREK channel subtype underlies I Ril."
29928032
reach
"All these factors and the fact that the outward current activated by riluzole was strongly reduced by spadin, a drug not affecting TASK-1 nor TRESK channels [XREF_BIBR, XREF_BIBR] indicate that channels of the TREK subfamily should be mediating I Ril."
29928032
KCNK2 affects NTSR3
| 2
KCNK2 binds NTSR3. 2 / 2
| 2
reach
"In physiological conditions (XREF_FIG), TREK-1 and NTSR3 and Sortilin would associate in the TGN vesicle, where spadin is hydrolyzed by furin."
20405001
reach
"This interaction between TREK-1 and NTSR3 and Sortilin led us to examine whether NT and/or the partial NTSR3 and Sortilin propeptide (i.e. spadin) were able to act on TREK-1 channel activity."
20405001
KCNK2 affects GYS
| 2
Modified KCNK2 leads to the dephosphorylation of GYS on S473. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
Modified KCNK2 leads to the dephosphorylation of GYS on S9. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
KCNK2 affects G betagamma
| 2
KCNK2 binds G betagamma. 1 / 1
| 1
reach
"Finally, we tested whether TREK-1-mediated glutamate release requires direct binding of G betagamma to TREK-1 by utilizing the N-terminal segments of TREK-1 to compete for binding of G betagamma to TREK-1."
23021213
KCNK2 binds G betagamma and glutamate. 1 / 1
| 1
reach
"To answer the question, we considered a possibility that G betagamma directly binds to TREK-1 to open a glutamate permeable channel."
23021213
KCNK2 affects Cyclin
| 2
Modified KCNK2 decreases the amount of Cyclin. 2 / 2
| 2
reach
"Overexpression of TREK-1 caused CHO cells arresting at the G1 phase, and significantly decreased the expression of cyclin D1."
27397543
reach
"Although the mechanism by which TREK-1 expression affects cellular functions remains unclear, it is believed, under hypoxic conditions, that the upregulation of TREK-1 expression inhibits the activity of protein kinase A and the expression of cyclin D1 [XREF_BIBR] and decreases neuronal stem cell [XREF_BIBR], astrocyte [XREF_BIBR], and human osteoblasts proliferation [XREF_BIBR, XREF_BIBR]."
28053983
KCNK2 affects Cell Hypoxia
| 2
KCNK2 inhibits Cell Hypoxia. 2 / 2
| 2
reach
"In addition, upregulation of Kcnk2 or knockdown of Foxd3 promoted the cell viability and reduced the apoptosis of the H/R treated PC12 cells."
31959866
reach
"Kcnk2 overexpression enhanced the viability and inhibited the apoptosis of the H/R treated PC12 cells."
31959866
KCNK2 affects CEL
| 1 1
KCNK2 binds CEL.
| 1
CEL binds IL6, KCNK2, and CCL2. 1 / 1
| 1
sparser
"Interestingly, the decrease in BAL fluid IL-6 and MCP-1 levels was associated with increased cellular apoptosis in TREK-1 deficient mice exposed to HO+MV."
25126877
KCNK2 activates CEL.
| 1
KCNK2 activates CEL. 1 / 1
| 1
reach
"Exposure to a combination of hyperoxia and injurious mechanical ventilation resulted in further morphological lung damage, increased LIS and BAL fluid cell numbers in control but not TREK-1 deficient mice."
25126877
KCNK2 affects Actin
| 1 2
KCNK2 binds Actin.
| 1
Actin binds KCNK2. 1 / 1
| 1
reach
"XREF_BIBR These findings suggest that the interaction between TREK-1 and actin through ezrin is involved in the translocation of TREK-1 channels and the current run-up."
28085542
KCNK2 activates Actin.
| 1 1
KCNK2 activates Actin. 1 / 1
| 1 1
reach
"Exposure of TREK-1 deficient cells to 2 or 6 hours of jasplakinolide increased the F/total actin content by 57% and 85%, respectively, but the combination of TNF-alpha+ jasplakinolide had no further effect on the F/total actin content when compared to jasplakinolide alone (XREF_FIG)."
26001192
KCNK2 affects AKT
| 2
Modified KCNK2 leads to the dephosphorylation of AKT on S473. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
Modified KCNK2 leads to the dephosphorylation of AKT on S9. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
KCNK2 affects 3',5'-cyclic AMP
| 2
Modified KCNK2 leads to the dephosphorylation of 3',5'-cyclic AMP on S9. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
Modified KCNK2 leads to the dephosphorylation of 3',5'-cyclic AMP on S473. 1 / 1
| 1
reach
"Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt (S473), glycogen synthase kinase-3beta (S9) and cAMP response element binding protein (CREB, S133), enhanced the phosphorylation of p38 (T180 and Y182), but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 (STAT3)."
27397543
IQ affects KCNK2
| 2
IQ inhibits KCNK2. 2 / 2
| 2
reach
"In this study, we demonstrate, for the first time, that IQ inhibits K v 1.1 and K v 1.2 and TREK1 and TRAAK."
22233604
reach
"These results indicated that IQ directly blocks TREK1 and TRAAK channels, which provide the background leakage current in DRG neurons."
22233604
IL6 affects KCNK2
| 1 1
IL6 binds KCNK2.
| 1
CEL binds IL6, KCNK2, and CCL2. 1 / 1
| 1
sparser
"Interestingly, the decrease in BAL fluid IL-6 and MCP-1 levels was associated with increased cellular apoptosis in TREK-1 deficient mice exposed to HO+MV."
25126877
IL6 activates KCNK2.
| 1
IL6 activates KCNK2. 1 / 1
| 1
reach
"These data give important insight into the regulatory mechanisms underlying IL-6 and MCP-1 production and secretion in TREK-1 deficient AECs."
26001192
GI-530139 affects KCNK2
| 2
GI-530139 activates KCNK2. 2 / 2
| 2
reach
"Activation of recombinant TREK channels by GI-530139."
29150838
reach
"This is shown as an inset to Figure XREF_FIG B and illustrates that the TREK1 current is enhanced at all voltages by GI-530139 and that the enhanced current is outwardly rectifying."
29150838
FASLG affects KCNK2
| 2
FASLG inhibits KCNK2. 2 / 2
| 2
reach
"Inhibition of TREK-1 by SPA induced a decrease of the resting membrane potential (DeltaV m ~ 12mV) and increased the cytosolic calcium concentration."
28105440
reach
"As shown in XREF_FIG, TREK-1 current was potentiated by 10muM arachidonic acid (AA) and application of SPA (10 -6 M) inhibited the AA activated TREK-1 current."
28105440
Ala-Asp-Ser affects KCNK2
| 2
Ala-Asp-Ser activates KCNK2. 2 / 2
| 2
reach
"Interestingly, in several behavior tests, Kcnk2 -/- mice behave, similarly, to naive mice treated with ADs like fluoxetine."
30127743
reach
"Indeed, this phenotype was comparable to that of Kcnk2 -/- mice (lacking TREK-1) which behaved as wild-type mice treated with classical ADs."
30127743
Actin affects KCNK2
| 2
Actin inhibits KCNK2.
| 1
Actin inhibits KCNK2. 1 / 1
| 1
reach
"21 Sarcolemmal TREK channels are inhibited by actin, 143 while Piezo1 channels need the actin cytoskeleton to fully activate."
26838316
Actin binds KCNK2.
| 1
Actin binds KCNK2. 1 / 1
| 1
reach
"XREF_BIBR These findings suggest that the interaction between TREK-1 and actin through ezrin is involved in the translocation of TREK-1 channels and the current run-up."
28085542
AVP affects KCNK2
| 1 1
AVP inhibits KCNK2. 2 / 2
| 1 1
sparser
"Both AngII and vasopressin strongly inhibited (~70–80%) TREK1 and depolarized the cells by ~30 mV [ xref ]."
25476848
reach
"Direct activation of protein kinase C (PKC) reduced the TREK-1 current, whereas PKC inhibition attenuated the AVP mediated reduction of the TREK-1 current, implicating the involvement of PKC."
26248219
5alpha-cholestane-3beta,5,6beta-triol affects KCNK2
| 2
5alpha-cholestane-3beta,5,6beta-triol activates KCNK2. 2 / 2
| 2
reach
"These findings suggest a general involvement of the C-type gate in K 2P 2.1 (TREK-1) activation by Ct, regardless of the modality used to control the channel and lead us to search for the mechanism that connects the action of Ct to the C-type gate."
22728824
reach
"The data presented here show that intracellular Ct mediates K 2P 2.1 (TREK-1) response to a wide range of signals by controlling the extracellular C-type gate."
22728824
(S)-lactate affects KCNK2
| 2
(S)-lactate increases the amount of KCNK2. 2 / 2
| 2
reach
"We propose that l-lactate promotes neuronal survival in hippocampus by increasing TREK1 channel expression via PKA pathway in astrocytes during ischaemia."
27062641
reach
"We show that 15-30mmol/L l-lactate increases functional TREK1 protein expression by 1.5-3-fold in hippocampal astrocytes using immunostaining and electrophysiology."
27062641
(R)-noradrenaline affects KCNK2
| 2
(R)-noradrenaline inhibits KCNK2. 2 / 2
| 2
reach
"Noradrenaline inhibits a rat atrial TREK like K (+) channel current via a PTX sensitive mechanism involving co-operativity of beta1- and beta2-adrenoceptors that contributes to atrial APD prolongation."
25205295
reach
"Noradrenaline inhibits a rat atrial TREK like K + channel current via a PTX sensitive mechanism involving co-operativity of beta 1 -/beta 2 -adrenoceptors that contributes to atrial APD prolongation."
25205295
Trans-aconitic acid affects KCNK2
| 1
Trans-aconitic acid activates KCNK2. 1 / 1
| 1
sparser
"Very recently, these authors have extended this work by developing a series of substituted acrylic acids, which activate TREK1 channels and show anti‐nociceptive activity in vivo (Vivier et al ., xref )."
29150838
Tetrapentylammonium affects KCNK2
| 1
Tetrapentylammonium inhibits KCNK2. 1 / 1
| 1
reach
"Considering that the same threonine amino acid residues are necessary for the tetrapentylammonium block of TREK-1 as for the inhibition of the channel by barium, the rate of inhibition by Ba 2+ should be the same for the resting and activated state."
29763475
Spectrin affects KCNK2
| 1
KCNK2 binds spectrin. 1 / 1
| 1
reach
"In contrast, SAN myocytes from qv 4J mice lacking spectrin and TREK -1 interaction8 demonstrated abnormal membrane localization of TREK-1."
27098968
Sodium atom affects KCNK2
| 1
Sodium atom activates KCNK2. 1 / 1
| 1
reach
"Flufenamic acid (FA, 100 microM), niflumic acid (NA, 100 microM), and mefenamic acid (MA, 100 microM) markedly stimulated TREK-1, TREK-2, and TRAAK."
16075240
Ruthenium red affects KCNK2
| 1
Ruthenium red inhibits KCNK2. 1 / 1
| 1
sparser
"However, ruthenium red inhibits the I110D TREK-1 mutant, which has one isoleucine mutated to aspartate within its extracellular ion pathway xref ."
28851868
Riluzole-, ML67-33- affects KCNK2
| 1
Riluzole-, ML67-33- activates KCNK2. 1 / 1
| 1
reach
"Fluoxetine, a strong inhibitor of the riluzole-, ML67-33- and BL-1249-activated currents, also blocks TREK-1 with more potency than TREK-2, whilst TRAAK currents are essentially insensitive [XREF_BIBR, XREF_BIBR]."
29928032
Riluzole affects KCNK2
| 1
Riluzole activates KCNK2. 1 / 1
| 1
reach
"This article reports that riluzole is an activator of TREK-1 and TRAAK, two important members of a new structural family of mammalian background K (+) channels with four transmembrane domains and two pore regions."
10779373
Pyruvic acid affects KCNK2
| 1
Pyruvic acid increases the amount of KCNK2. 1 / 1
| 1
reach
"The above effects were specific to l-lactate as pyruvate failed to increase TREK1 expression and reduce cell death."
27062641
Prostaglandin E2 affects KCNK2
| 1
Prostaglandin E2 inhibits KCNK2. 1 / 1
| 1
reach
"In this case, the effect was attributed to removal of an ion channel that normally contributes to actions of inflammatory mediators (e.g. TREK-1 inhibition by prostaglandin E2)."
18823665
Postsynaptic beta-adrenergic receptors affects KCNK2
| 1
Postsynaptic beta-adrenergic receptors inhibits KCNK2. 1 / 1
| 1
reach
"Leak-type TREK K + currents can be inhibited by the stimulation of postsynaptic beta-adrenergic receptors in mPFC pyramidal neurons."
29209170
Paroxetine affects KCNK2
| 1
Paroxetine inhibits KCNK2. 1 / 1
| 1
reach
"Application of 10 muM fluoxetine, 20 muM paroxetine, 100 muM citalopram, and 30 muM chlorpromazine significantly inhibited TREK-1 currents by 28 +/- 11%, 40 +/- 9%, 31 +/- 10%, and 52 +/- 10%, respectively (p < 0.05, XREF_FIG a-c)."
29156592
P-cresol sulfate affects KCNK2
| 1
P-cresol sulfate binds KCNK2. 1 / 1
| 1
sparser
"This result indicated that the TREK1-PCS co-assembles with WT-TREK1 subunits and that the heteromeric channel (TREK1-PCS/WT-TREK1) goes to the cell surface where it is regulated by light via photoisomerization of MAQ attached to the TREK1-PCS subunit."
23596388
Oxaliplatin affects KCNK2
| 1
Oxaliplatin decreases the amount of KCNK2. 1 / 1
| 1
reach
"Interestingly, oxaliplatin reduces TREK1 and TRAAK expression, and double KOs have modified cold pain responses in this model XREF_BIBR."
24461875
Octan-1-ol affects KCNK2
| 1
Octan-1-ol inhibits KCNK2. 1 / 1
| 1
reach
"Using the cutoff determined with PLD2 as a prediction for TREK-1 inhibition and using whole cell patch clamp as a measurement, we found that octanol (8 carbons) and ethanol robustly inhibit TREK-1 currents in HEK293 cells expressing TREK-1 channels (XREF_FIG and XREF_SUPPLEMENTARY)."
30529033
Nitroprusside affects KCNK2
| 1
Nitroprusside activates KCNK2. 1 / 1
| 1
reach
"Sodium nitroprusside (10 (-6) or 10 (-5) m) and 8-Br-cGMP (10 (-4) or 10 (-3) m) increased TREK-1 currents in perforated whole cell and single channel recordings."
11560940
Nitric oxide affects KCNK2
| 1
Nitric oxide activates KCNK2. 1 / 1
| 1
reach
"NO increases open probability of TREK channels in colonic muscles, and stretch further activates these channels, possibly in a synergistic manner with cGMP dependent phosphorylation."
23279087
Microtubule-associated protein Mtap2 affects KCNK2
| 1
Microtubule-associated protein Mtap2 increases the amount of KCNK2. 1 / 1
| 1
reach
"To date, the only identified partner proteins of TREK-1 channels are the A-kinase anchoring protein AKAP150 XREF_BIBR and the microtubule associated protein Mtap2 XREF_BIBR that enhance TREK-1 channel surface expression and current densities."
20405001
MiR-214 affects KCNK2
| 1
MiR-214 activates KCNK2. 1 / 1
| 1
reach
"Notably, Foxd3 activated miR-214, and miR-214 targeted Kcnk2."
31959866
MiR-183-5p affects KCNK2
| 1
KCNK2 binds miR-183-5p. 1 / 1
| 1
reach
"Luciferase assays confirmed the binding of miR-183-5p and TREK-1."
29736614
Mefenamic acid affects KCNK2
| 1
Mefenamic acid activates KCNK2. 1 / 1
| 1
reach
"Flufenamic acid (FA, 100 microM), niflumic acid (NA, 100 microM), and mefenamic acid (MA, 100 microM) markedly stimulated TREK-1, TREK-2, and TRAAK."
16075240
LnpA affects KCNK2
| 1
LnpA inhibits KCNK2. 1 / 1
| 1
reach
"All values were expressed as mean +/- SD, and the number of cells (n) in each group was given, P < 0.05 was considered to be statistically significant.Our previous studies showed that selective TREK-1 inhibitor l-NBP potently inhibited TREK-1 currents both in CHO and TREK -1 cells and cadiomyocytes [19,20]."
29438799
Linoleic acid affects KCNK2
| 1
Linoleic acid activates KCNK2. 1 / 1
| 1
reach
"Docosahexaenoic acid, linolenic acid and linoleic acid have been shown to directly stimulate two-pore domain potassium channel (TREK and TRAAK channels) which causes hyperpolarization and promotes vascular relaxation XREF_BIBR."
23409085
Lead(2+) affects KCNK2
| 1
Lead(2+) inhibits KCNK2. 1 / 1
| 1
reach
"Pb (2+) inhibited TREK channel activity (IC (50) = 15.6 microM), whereas Zn (2+) enhanced it in a dose dependent manner (EC (50) = 87.1 microM)."
15857947
Kn affects KCNK2
| 1
KCNK2 binds kn. 1 / 1
| 1
sparser
"Taken together, these data suggest that TREK-1 is associated with NSC proliferation and probably is a modulator of the effect that fluoxetine attenuates the inhibitory neurogenesis induced by glucocorticoid hormones."
21069514
Jaspamide affects KCNK2
| 1
Jaspamide activates KCNK2. 1 / 1
| 1
reach
"Jasplakinolide increased the F-actin content of TREK-1 deficient cells, similar to the effect of TREK-1 overexpression in control cells."
26001192
Ion channel affects KCNK2
| 1
Ion channel activates KCNK2. 1 / 1
| 1
reach
"Magnetic ion channel activation of TREK1 in human mesenchymal stem cells using nanoparticles promotes osteogenesis in surrounding cells."
30397432
Hsa-miR-8061 affects KCNK2
1 |
Transcriptionally active hsa-miR-8061 decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27418678
Hsa-miR-6809-3p affects KCNK2
1 |
Transcriptionally active hsa-miR-6809-3p decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-5696 affects KCNK2
1 |
Transcriptionally active hsa-miR-5696 decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27418678
Hsa-miR-5571-5p affects KCNK2
1 |
Transcriptionally active hsa-miR-5571-5p decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-4760-5p affects KCNK2
1 |
Transcriptionally active hsa-miR-4760-5p decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27418678
Hsa-miR-4753-3p affects KCNK2
1 |
Transcriptionally active hsa-miR-4753-3p decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-4729 affects KCNK2
1 |
Transcriptionally active hsa-miR-4729 decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27418678
Hsa-miR-4284 affects KCNK2
1 |
Transcriptionally active hsa-miR-4284 decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-3682-3p affects KCNK2
1 |
Transcriptionally active hsa-miR-3682-3p decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-24-3p affects KCNK2
1 |
Transcriptionally active hsa-miR-24-3p decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-124-3p affects KCNK2
1 |
Transcriptionally active hsa-miR-124-3p decreases the amount of KCNK2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
18668037
Hexadecanoic acid affects KCNK2
| 1
Hexadecanoic acid activates KCNK2. 1 / 1
| 1
reach
"Palmitic acid, a saturated fatty acid that does not activate the 2P-domain K-channel TREK and TRAAK family, did not provide any neuroprotection."
16289892
Glucose affects KCNK2
| 1
Glucose activates KCNK2. 1 / 1
| 1
reach
"A dedicated Multidisciplinary Physical Activity and Diabetes Clinic delivering individualised, evidence based, patient focused advice on the effects of altitude on blood glucose levels, and provision of real-time continuous glucose monitoring enabled uneventful completion of a trek to Everest Base Camp in a person with type 1 diabetes."
29021909
Glucocorticoid hormone receptor affects KCNK2
| 1
Glucocorticoid hormone receptor increases the amount of KCNK2. 1 / 1
| 1
reach
"Dexamethasone, a glucocorticoid hormone receptor agonist, upregulated both protein and mRNA levels of TREK-1 leading to decreased NSC proliferation which could be reversed by bupivacaine."
21069514
Gate affects KCNK2
| 1
Gate activates KCNK2. 1 / 1
| 1
reach
"In addition to temperature, the C-type gate mediates TREK-1 gating by intracellular pH, extracellular pH, a small molecule activator ML67-33, phosphorylation, and, possibly, membrane stretch."
25366235
Gag affects KCNK2
| 1
Gag activates KCNK2. 1 / 1
| 1
reach
"Flufenamic acid (FA, 100 microM), niflumic acid (NA, 100 microM), and mefenamic acid (MA, 100 microM) markedly stimulated TREK-1, TREK-2, and TRAAK."
16075240
Dominant-negative TREK-1 mutant affects KCNK2
| 1
Dominant-negative TREK-1 mutant inhibits KCNK2. 1 / 1
| 1
reach
"Moreover, the increased cell proliferation rate of PC3 cells and TREK-1 overexpressing CHO cells could be reduced when TREK-1 current was reduced by overexpression of a dominant negative TREK-1 mutant or when cells were exposed to a TREK-1 inhibitor."
18281496
DnAMPK affects KCNK2
| 1
DnAMPK inhibits KCNK2. 1 / 1
| 1
reach
"In addition, prolonged exposure (6-7 min) to hypoxia (= 11 +/- 1 mmHg) inhibits TREK channels and this response was blocked by expression of dnAMPK."
19840997
Dimethyl sulfoxide affects KCNK2
| 1
Dimethyl sulfoxide inhibits KCNK2. 1 / 1
| 1
reach
"First, DMSO did not inhibit growth of K 2P 2.1 (TREK-1)-expressing yeast in potassium limiting conditions (2 mM KCl) where the active channel is required for survival, whereas SDS was lethal."
23738709
Dihydrogen affects KCNK2
| 1
Dihydrogen inhibits KCNK2. 1 / 1
| 1
sparser
"DEPC has been shown to prevent inhibition of TREK1 by protons ( xref ), thus leading to an increased current density at physiological pH e ."
20605797
Dexamethasone affects KCNK2
| 1 1
Dexamethasone increases the amount of KCNK2. 1 / 1
| 1 1
reach
"Dexamethasone, a glucocorticoid hormone receptor agonist, upregulated both protein and mRNA levels of TREK-1 leading to decreased NSC proliferation which could be reversed by bupivacaine."
21069514
Copper atom affects KCNK2
| 1
Copper atom activates KCNK2. 1 / 1
| 1
sparser
"Copper activates TREK-1 channels by 83 +/- 11% with an EC(50) of 3.0 +/- 1.0 microM, whereas TASK-3 channels are potently inhibited, with an IC(50) of 2.7 +/- 0.4 microM."
15322244
Chloroform affects KCNK2
| 2 1
Chloroform activates KCNK2. 1 / 1
| 2 1
sparser
"Tissue studies have been performed on these K + channels. xref examined TASK and TREK-1, and found that TREK-1 was activated by chloroform, diethyl ether, halothane and isoflurane, while TASK was activated by halothane and isoflurane. xref engineered human TRESK channels into the Xenopus oocyte, and noted that their outward currents were potentiated 1.5- to 3-fold by different haloalkane GAs. xref expressed TREK-1 channels on HEK-293 cells and showed that TREK-1 currents were enhanced by nitrous oxide, xenon, cyclopropane and halothane. xref cloned a TASK channel from the mollusc Lymnaea stagnalis and discovered that it was preferentially activated by (+)-isoflurane; this was also observed in mice ( xref and rats ( xref ."
20735416
Calcium(2+) affects KCNK2
| 1
Calcium(2+) inhibits KCNK2. 1 / 1
| 1
reach
"The inhibition of TREK by Ca 2+ is somewhat curious, because TREK in general is not thought of as a Ca 2+ -sensitive channel."
25476848
Alpha-linolenic acid affects KCNK2
| 1
Alpha-linolenic acid activates KCNK2. 1 / 1
| 1
reach
"Docosahexaenoic acid, linolenic acid and linoleic acid have been shown to directly stimulate two-pore domain potassium channel (TREK and TRAAK channels) which causes hyperpolarization and promotes vascular relaxation XREF_BIBR."
23409085
Alpha-Spec affects KCNK2
| 1
KCNK2 binds alpha-Spec. 1 / 1
| 1
sparser
"More specifically, βIV spectrin and TREK-1 associate, and βIV spectrin is required for TREK-1 localization and function in ventricular myocytes (Hund et al., xref )."
29163198
Adenosine 5'-monophosphate affects KCNK2
| 1
Adenosine 5'-monophosphate inhibits KCNK2. 1 / 1
| 1
reach
"AMP activated protein kinase inhibits TREK channels."
19840997
Zinc affects KCNK2
| 1
Zinc activates KCNK2. 1 / 1
| 1
reach
"Zinc has dual effects, blocking TASK-2, TASK-3 and TWIK-2 channels yet also activates TREK-1 and TREK-2 [XREF_BIBR]; with these opposing effects, it is difficult to discern the precise target of action of this divalent cation."
23305490
US affects KCNK2
| 1
US activates KCNK2. 1 / 1
| 1
reach
"These data suggest that US activated the TREK-1 ion channel."
27112990
UBA2 affects KCNK2
| 1
UBA2 activates KCNK2. 1 / 1
| 1
sparser
"Our results demonstrate that all four 2-P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP2."
15677683
TRESK-MT2 affects KCNK2
| 1
TRESK-MT2 inhibits KCNK2. 1 / 1
| 1
reach
"fsATI leads to the production of a second protein fragment, TRESK-MT2, which co-assembles with and inhibits TREK1 and TREK2, two other two-pore-domain K+ channels, to increase trigeminal sensory neuron excitability, leading to a migraine like phenotype in rodents."
30573346
TREK1DeltaEx4 affects KCNK2
| 1
TREK1DeltaEx4 decreases the amount of KCNK2. 1 / 1
| 1
reach
"Additionally, TREK1DeltaEx4 reduced the level of TREK1 expression in the plasma membrane."
20605797
TREK-1 modulators affects KCNK2
| 1
TREK-1 modulators activates KCNK2. 1 / 1
| 1
reach
"The development of specific TREK-1 modulators would allow a better understanding of the implication of TREK-1 in this area.Our former results indicated that mRNA and protein expressions of TREK-1 were increased in acute and chronic cerebral ischemic rat models [5,6]."
29438799
TPenA affects KCNK2
| 1
TPenA inhibits KCNK2. 1 / 1
| 1
reach
"TPenA inhibition of TREK-1 was, therefore, measured for pH values ranging from pH 7.0 to pH 5.0 and found to be identical despite the fact that the N * Po (i.e., activated current) increased> 30-fold (XREF_FIG)."
21822218
TP63 affects KCNK2
| 1
TP63 inhibits KCNK2. 1 / 1
| 1
sparser
"1-NBP potently inhibited TREK-1 current and elevated the membrane potential, which may contribute to its neuroprotective activity."
21293470
TGOLN2 affects KCNK2
| 1
TGOLN2 binds KCNK2. 1 / 1
| 1
sparser
"In physiological conditions ( xref ), TREK-1 and NTSR3/Sortilin would associate in the TGN vesicle, where spadin is hydrolyzed by furin."
20405001
Stretch affects KCNK2
| 1
Stretch activates KCNK2. 1 / 1
| 1
reach
"Stretch activation of TREK-1 was also significantly impaired by PC2-D509V co-expression, another pathogenic mutant reported to exert a dominant negative effect (XREF_FIG)."
22832196
SSRI fluoxetine affects KCNK2
| 1
SSRI fluoxetine activates KCNK2. 1 / 1
| 1
reach
"Spadin was administered 30 min before the test by intracerebroventricular (i.c.v.), intravenous (i.v.), or intraperitoneal (i.p.) route at doses of 10 -4 to 10 -8 M. Its effects were compared to the behavior observed in kcnk2 -/- mice and in wild-type mice treated with the efficient SSRI fluoxetine (i.p., 3 mg/kg)."
20405001
SPTBN4 affects KCNK2
| 1
SPTBN4 binds KCNK2. 1 / 1
| 1
reach
"Interestingly, TREK-1 in myocytes interacts with betaIV-spectrin and AnkyrinG [XREF_BIBR], which are involved in membrane targeting and complex formation of a number of cardiac ion channels [XREF_BIBR]."
27347491
SLC7A7 affects KCNK2
| 1
SLC7A7 activates KCNK2. 1 / 1
| 1
sparser
"Similarly, it has been shown that LPI activates TREK channels such as bTREK-1 and bKv1.4 K + currents [ xref ]."
26784247
SLC44A2 affects KCNK2
| 1
SLC44A2 binds KCNK2. 1 / 1
| 1
sparser
"A direct or functional interaction with either TREK-1 or slc44a2 is yet to be shown in the TM cells."
22496787
SIT1 affects KCNK2
| 1
SIT1 increases the amount of KCNK2. 1 / 1
| 1
reach
"SIT can restore the expression of Trek1 in the nasal epithelia and can be further improved by conjunction with administration of C. butyricum."
25529528
SID1900 affects KCNK2
| 1
SID1900 inhibits KCNK2. 1 / 1
| 1
reach
"Electrophysiological research has shown that SID1900 and the previously reported TREK1 blocker (spadin) efficiently blocked TREK-1 current in HEK293 cells and specifically blocked two-pore domain potassium channels in primary cultured rat hippocampal neurons."
26441141
SFTPA2 affects KCNK2
| 1
SFTPA2 inhibits KCNK2. 1 / 1
| 1
sparser
"Inhibition of TREK-1 by SPA induced a decrease of the resting membrane potential (Δ V m ~ 12 mV) and increased the cytosolic calcium concentration."
28105440
Rb affects KCNK2
| 1
Rb activates KCNK2. 1 / 1
| 1
reach
"Strikingly, replacement of intracellular K + by Rb + increased the voltage dependent activation of TREK-1 around 100-fold, resulting in large outward currents and large tail currents (XREF_FIG A)."
26919430
RB1 affects KCNK2
| 1
RB1 activates KCNK2. 1 / 1
| 1
sparser
"Therefore we tested the “lipid occlusion” model of mechanogating ( xref ) by comparing stretch and Rb + activation of TREK-1 channels expressed in Xenopus oocytes ( xref )."
28392258
QPCT affects KCNK2
| 1
QPCT activates KCNK2. 1 / 1
| 1
reach
"A total of 72 bacteria-antibiotic combinations were analysed, resulting in 97% agreement between the results obtained by the oCelloScope system and the TREK target QC range."
26407621
QA L affects KCNK2
| 1
QA L inhibits KCNK2. 1 / 1
| 1
reach
"Furthermore, TREK-1 activation with 2-APB or ML335 was not antagonized by QA L + inhibition and mutations at the BL-1249 site did not affect 2-APB activation (XREF_SUPPLEMENTARY)."
30792303
Popdc1 affects KCNK2
| 1
KCNK2 binds Popdc1. 1 / 1
| 1
sparser
"This concept finds support from our analysis of the interaction of TREK-1 and Popdc1 in Xenopus oocytes."
24646234
Popdc affects KCNK2
| 1
KCNK2 binds Popdc. 1 / 1
| 1
reach
"However, at present, the effect of this instantaneous conformational change of the Popdc and TREK-1 complex on channel properties is not understood."
24646234
Plenti-TREK-1-GFP affects KCNK2
| 1
Plenti-TREK-1-GFP increases the amount of KCNK2. 1 / 1
| 1
reach
"As demonstrated in XREF_FIG, Plenti-TREK-1-GFP infection significantly increased TREK-1 expression in astrocytes compared with Plenti-sham-GFP infection cells (P < 0.05), and TREK-1 overexpression exhibited similar effects to the isoflurane dependent changes in the expression of BDNF, Bax and caspase-3, as TREK-1 overexpression reduced the expression of BDNF, and increased the expression of Bax and caspase-3, which was also observed for isoflurane treatment in XREF_FIG."
28944872
PSTPIP1 affects KCNK2
| 1
KCNK2 binds PSTPIP1. 1 / 1
| 1
sparser
"Consistent with direct lipid binding, we found mutating R297 to cysteine completely blocked 500 nM 3 H-PIP 2 binding to TREK-1 ( xref )."
28793254
PLD affects KCNK2
| 1
PLD activates KCNK2. 1 / 1
| 1
reach
"PLD localizes with and activates TREK-1 through production of PA [XREF_BIBR] and PG [XREF_BIBR, XREF_BIBR]."
30529033
PK-THPP affects KCNK2
| 1
PK-THPP inhibits KCNK2. 1 / 1
| 1
reach
"PK-THPP inhibits TREK-1, Kv1.5, hERG and K ATP potassium channels with IC 50 s (in muM) of> 10, ~ 5,> 15, and> 10, respectively."
23460565
PALM affects KCNK2
| 1
PALM inhibits KCNK2. 1 / 1
| 1
reach
"Palm oil, being rich in polyunsaturated fatty acids especially linoleic acid (13.6% in SO, 12.2% in RPO and 11.3% in PO, XREF_TABLE), may partly inhibit the rise of BP in the SHR by modulating the TREK and TRAAK channels."
23409085
NPS-ACTH affects KCNK2
| 1
NPS-ACTH inhibits KCNK2. 1 / 1
| 1
reach
"Second, TREK-1 inhibition by NPS-ACTH was insensitive to PKA inhibitors."
18663135
NPS affects KCNK2
| 1
NPS inhibits KCNK2. 1 / 1
| 1
sparser
"Second, TREK-1 inhibition by NPS-ACTH was insensitive to PKA inhibitors."
18663135
Mechano affects KCNK2
| 1
Mechano activates KCNK2. 1 / 1
| 1
reach
"Mechano activation of TREK-1 does not involve gating at the bundle crossing."
21822218
MDEL7 affects KCNK2
| 1
MDEL7 activates KCNK2. 1 / 1
| 1
reach
"Heat is often mediated bytransient receptor potential cation channel subfamily V member 1-3 (TRPV1-3) and TREK1, mechanical pressure is mediated by the MDEL7 and TREK1 and acid or chemical stimulus is mediated by acid sensing ion channel (ASIC) [XREF_BIBR]."
29226044
MCP-1 affects KCNK2
| 1
MCP-1 activates KCNK2. 1 / 1
| 1
reach
"These data give important insight into the regulatory mechanisms underlying IL-6 and MCP-1 production and secretion in TREK-1 deficient AECs."
26001192
LPS with O-antigen affects KCNK2
| 1
LPS with O-antigen inhibits KCNK2. 1 / 1
| 1
reach
"We demonstrate that lysophospholipids (LPs) and platelet activating factor also produce large specific and reversible activations of TREK-1 and TRAAK."
10744694
LIN affects KCNK2
| 1
LIN activates KCNK2. 1 / 1
| 1
sparser
"Additional TREK-1 activation in neurons by LIN or LPC would provide further protection [ xref ]."
18823665
KCNK2 affects transport
| 1
KCNK2 inhibits transport. 1 / 1
| 1
reach
"Activation of TREK-1, an inward rectifying K + channel XREF_BIBR prevents inward DiBAC transport resulting in lower fluorescence."
21886777
KCNK2 affects spectrin
| 1
KCNK2 binds spectrin. 1 / 1
| 1
reach
"In contrast, SAN myocytes from qv 4J mice lacking spectrin and TREK -1 interaction8 demonstrated abnormal membrane localization of TREK-1."
27098968
KCNK2 affects serotonin
| 1
Serotonin binds KCNK2. 1 / 1
| 1
reach
"This study examined associations between serotonin and TREK1 by evaluating how pharmacologically manipulated (via chronic fluoxetine administration) as well as genetically conferred (SLC6A4; 5-HTTLPR genotype), differences in serotonin transporter function are linked to cortical TREK1 protein expression in rhesus monkeys."
21871532
KCNK2 affects phosphatidic acid
| 1
KCNK2 activates phosphatidic acid. 1 / 1
| 1
reach
"Incorporation of TREK-1 appeared to increase with 15 mol% PA compared with 10 mol% (the GFP fluorescence increased to 17,800 RU; p = 0.02, unpaired Student 's t test)."
28793254
KCNK2 affects p-cresol sulfate
| 1
P-cresol sulfate binds KCNK2. 1 / 1
| 1
sparser
"This result indicated that the TREK1-PCS co-assembles with WT-TREK1 subunits and that the heteromeric channel (TREK1-PCS/WT-TREK1) goes to the cell surface where it is regulated by light via photoisomerization of MAQ attached to the TREK1-PCS subunit."
23596388
KCNK2 affects muF
| 1
KCNK2 inhibits muF. 1 / 1
| 1
reach
"At the WT MDP of -57.6 mV, TREK-1 is about 9 times smaller than the major repolarizing current I Kr (0.0761 muA and muF versus 0.6549 muA and muF); however, TREK-1 increases during the spontaneous diastolic depolarization phase, whereas I Kr decreases (due to rapid inactivation) such that at -40 mV (close to takeoff potential), the 2 currents are much closer in amplitude (0.1628 muA and muF versus 0.4644 muA and muF)."
27098968
KCNK2 affects muA
| 1
KCNK2 inhibits muA. 1 / 1
| 1
reach
"At the WT MDP of -57.6 mV, TREK-1 is about 9 times smaller than the major repolarizing current I Kr (0.0761 muA and muF versus 0.6549 muA and muF); however, TREK-1 increases during the spontaneous diastolic depolarization phase, whereas I Kr decreases (due to rapid inactivation) such that at -40 mV (close to takeoff potential), the 2 currents are much closer in amplitude (0.1628 muA and muF versus 0.4644 muA and muF)."
27098968
KCNK2 affects monolayer barrier
| 1
KCNK2 inhibits monolayer barrier. 1 / 1
| 1
reach
"The results showed that Trek1 deficiency induced T84 monolayer barrier disruption."
25683610
KCNK2 affects methyl isothiocyanate
| 1
KCNK2 activates methyl isothiocyanate. 1 / 1
| 1
reach
"The broth microdilution (BMD) method QC study had nine participating laboratories and employed reference MIC panels produced by Trek Diagnostics (Cleveland, OH)."
29848564
KCNK2 affects localization
| 1
KCNK2 inhibits localization. 1 / 1
| 1
reach
"In the present study, we showed that decreased expression of TREK-1 in A549 cells caused changes in the cytoskeletal structure, localization of FAs, and an increase in cell deformability."
24586773
KCNK2 affects lactate
| 1
KCNK2 activates lactate. 1 / 1
| 1
reach
"Ischaemic concentrations of lactate increase TREK1 channel activity by interacting with a single histidine residue in the carboxy terminal domain."
26445100
KCNK2 affects kn
| 1
KCNK2 binds kn. 1 / 1
| 1
sparser
"Taken together, these data suggest that TREK-1 is associated with NSC proliferation and probably is a modulator of the effect that fluoxetine attenuates the inhibitory neurogenesis induced by glucocorticoid hormones."
21069514
KCNK2 affects gate
| 1
KCNK2 activates gate. 1 / 1
| 1
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"Here, we describe a new small molecule TREK activator class that directly stimulates the C-type gate by acting as molecular wedges that restrict interdomain interface movement behind the selectivity filter."
28693035
KCNK2 affects gamma-aminobutyric acid
| 1
KCNK2 inhibits gamma-aminobutyric acid. 1 / 1
| 1
reach
"[XREF_BIBR] Recent work has also shown that Trek channels mediate, in part, the inhibitory effect of GABA B receptor stimulation on neurons in the hippocampus and entorhinal cortex, [XREF_BIBR, XREF_BIBR] and have suggested a role for Trek channels in learning and memory."
28682878
KCNK2 affects ethanol
| 1
Ethanol binds KCNK2. 1 / 1
| 1
reach
"To further confirm that ethanol is not an allosteric antagonist, we tested ethanol binding to TREK-1 and TRAAK in our lipid binding assay [XREF_BIBR]."
30529033
KCNK2 affects curcumin
| 1
KCNK2 activates curcumin. 1 / 1
| 1
reach
"Evidence in favour of a contribution of TREK-1 in proliferative phase endometrium is corroborated by its higher expression during this period and our finding that the TREK-1 modulators curcumin and zinc modify cell proliferation."
23305490
KCNK2 affects channel subfamily V member 1-3
| 1
KCNK2 activates channel subfamily V member 1-3. 1 / 1
| 1
reach
"Heat is often mediated bytransient receptor potential cation channel subfamily V member 1-3 (TRPV1-3) and TREK1, mechanical pressure is mediated by the MDEL7 and TREK1 and acid or chemical stimulus is mediated by acid sensing ion channel (ASIC) [XREF_BIBR]."
29226044
KCNK2 affects cell differentiation
| 1
KCNK2 activates cell differentiation. 1 / 1
| 1
reach
"7 The resulting increase in the proteins Sox9, osteopontin and collagen provided evidence that a mechanical stimulation of TREK-1 is sufficient to induce the differentiation of osteoprogenitor cell populations toward an osteogenic lineage."
29163884
KCNK2 affects baclofen
| 1
KCNK2 activates baclofen. 1 / 1
| 1
reach
"In light of the 8Br-cAMP sensitivity and recent studies, the non Girk component of I Baclofen may be mediated by a two-pore domain Trek K + channel."
24094109
KCNK2 affects alpha-Spec
| 1
KCNK2 binds alpha-Spec. 1 / 1
| 1
sparser
"More specifically, βIV spectrin and TREK-1 associate, and βIV spectrin is required for TREK-1 localization and function in ventricular myocytes (Hund et al., xref )."
29163198
KCNK2 affects VV2 operator-splitting velocity Verlet integrator
| 1
KCNK2 activates VV2 operator-splitting velocity Verlet integrator. 1 / 1
| 1
reach
"The ones that are most commonly used are : QM/MM methods, the EEF1 solvation model, the replica (molecular replication) methods, the TREK reaction-path facility, the PERT free energy methods, targeted molecular dynamics, the HQBM external perturbation facility, adaptive umbrella sampling, soft core potentials, the Drude oscillator polarizable model, and the VV2 operator splitting velocity Verlet integrator."
19444816
KCNK2 affects TRPV1-3
| 1
KCNK2 activates TRPV1-3. 1 / 1
| 1
reach
"Heat is often mediated bytransient receptor potential cation channel subfamily V member 1-3 (TRPV1-3) and TREK1, mechanical pressure is mediated by the MDEL7 and TREK1 and acid or chemical stimulus is mediated by acid sensing ion channel (ASIC) [XREF_BIBR]."
29226044
KCNK2 affects TREK-1 mRNA
| 1
KCNK2 inhibits TREK-1 mRNA. 1 / 1
| 1
reach
"As demonstrated in XREF_FIG, Lv-shRNA-TREK-1 infection significantly decreased TREK-1 mRNA and protein expression (P < 0.05) in astrocytes compared with Lv-shRNA-sham cells, and inhibited the effect of 1.0 and 1.5 MAC isoflurane on the expression of TREK-1, BDNF, Bax and caspase-3 (P < 0.05)."
28944872
KCNK2 affects TREK-1 channels
| 1
KCNK2 activates TREK-1 channels. 1 / 1
| 1
reach
"The anxiolytic and antidepressive effect was diminished by co-administration of a TREK-1 blocker, amlodipine, indicating the involvement of TREK-1 channels."
30110354
KCNK2 affects TNF
| 1
TNF binds KCNK2. 1 / 1
| 1
reach
"This binding was selective since NT was unable to displace the binding of 125 I-spadin and the N-terminal fragment Gln1-Arg16 bound to TREK-1 with a very low affinity (1 microM) close to that reported with NTSR3 and sortilin (XREF_FIG) XREF_BIBR."
20405001
KCNK2 affects TGOLN2
| 1
TGOLN2 binds KCNK2. 1 / 1
| 1
sparser
"In physiological conditions ( xref ), TREK-1 and NTSR3/Sortilin would associate in the TGN vesicle, where spadin is hydrolyzed by furin."
20405001
KCNK2 affects SPTBN4
| 1
SPTBN4 binds KCNK2. 1 / 1
| 1
reach
"Interestingly, TREK-1 in myocytes interacts with betaIV-spectrin and AnkyrinG [XREF_BIBR], which are involved in membrane targeting and complex formation of a number of cardiac ion channels [XREF_BIBR]."
27347491
KCNK2 affects SNCG
| 1
KCNK2 activates SNCG. 1 / 1
| 1
reach
"Ad-TREK-1 increased the SR prevalence to 62% during follow-up in AF animals, compared to 35% in the untreated AF group."
28005193
KCNK2 affects SLC44A2
| 1
SLC44A2 binds KCNK2. 1 / 1
| 1
sparser
"A direct or functional interaction with either TREK-1 or slc44a2 is yet to be shown in the TM cells."
22496787
KCNK2 affects QPCT
| 1
KCNK2 activates QPCT. 1 / 1
| 1
reach
"A total of 72 bacteria-antibiotic combinations were analysed, resulting in 97% agreement between the results obtained by the oCelloScope system and the TREK target QC range."
26407621
KCNK2 affects Popdc1
| 1
KCNK2 binds Popdc1. 1 / 1
| 1
sparser
"This concept finds support from our analysis of the interaction of TREK-1 and Popdc1 in Xenopus oocytes."
24646234
KCNK2 affects Popdc
| 1
KCNK2 binds Popdc. 1 / 1
| 1
reach
"However, at present, the effect of this instantaneous conformational change of the Popdc and TREK-1 complex on channel properties is not understood."
24646234
KCNK2 affects PSTPIP1
| 1
KCNK2 binds PSTPIP1. 1 / 1
| 1
sparser
"Consistent with direct lipid binding, we found mutating R297 to cysteine completely blocked 500 nM 3 H-PIP 2 binding to TREK-1 ( xref )."
28793254
KCNK2 affects PLD2, and phospholipase
| 1
KCNK2 binds PLD2 and phospholipase. 1 / 1
| 1
reach
"PA appears to activate TREK-1 as phospholipase D2 (PLD2) directly binds to TREK-1 and activates the channel through local production of lipid."
28793254
KCNK2 affects PCNA
| 1
KCNK2 activates PCNA. 1 / 1
| 1
reach
"We developed an MLE-12 cell line deficient in Trek-1 expression using shRNA and found that Trek-1 deficiency resulted in increased cell proliferation and upregulation of PCNA but not Cyclin D1."
21949155
KCNK2 affects OXT
| 1
KCNK2 activates OXT. 1 / 1
| 1
reach
"The TREK-1 blocker l-methionine enhanced oxytocin contraction in Singleton-Term and twin pregnant uterus, and reversed the decreases in contraction in uterine strips exposed to prolonged stretch."
29577872
KCNK2 affects N-methyl-D-aspartic acid
| 1
KCNK2 activates N-methyl-D-aspartic acid. 1 / 1
| 1
reach
"TREK-1, the product of the kcnk2 gene, regulates cell excitability and prevents neuron death by inhibiting NMDA dependent glutamatergic excitotoxicity induced by ischemia."
26909044
KCNK2 affects MCF2L2
| 1
KCNK2 inhibits MCF2L2. 1 / 1
| 1
reach
"The upregulation of TREK-1 channel in DRG might suppress the excitability of DRG neurons and play a protective role in DO rats."
29462125
KCNK2 affects MAPK
| 1
KCNK2 activates MAPK. 1 / 1
| 1
reach
"TREK-1 overexpression suppresses CHO cell proliferation by inhibiting the activity of PKA and p38 and MAPK signaling pathways and subsequently inducing G1 phase cell arrest."
27397543
KCNK2 affects LPS with O-antigen
| 1
KCNK2 inhibits LPS with O-antigen. 1 / 1
| 1
reach
"The Knockdown of TREK-1 in Hippocampal Neurons Attenuate Lipopolysaccharide Induced Depressive Like Behavior in Mice."
31771312
KCNK2 affects L2
| 1
KCNK2 activates L2. 1 / 1
| 1
reach
"In contrast, we found no impact of Trek channel ablation on morphine induced CPP."
22973213
KCNK2 affects KCNK4, and phosphatidylinositol phosphate
| 1
Phosphatidylinositol phosphate binds KCNK2 and KCNK4. 1 / 1
| 1
sparser
"Consistent with the ion flux data, ethanol had no effect on PIP 2 binding to TREK-1 or TRAAK ( xref ) while norfluoxetine (NFX), a TREK-1 specific allosteric antagonist[ xref ], completely blocked PIP 2 binding (p<0.0001) to TREK-1."
30529033
KCNK2 affects KCNK4, PKD1, and PKD2
| 1
KCNK2 binds KCNK4, PKD1, and PKD2. 1 / 1
| 1
sparser
"In renal epithelial cells, PKD1 and PKD2 interact with the stretch activated potassium channels TREK-1 and TRAAK to protect against mechanical strain induced apoptosis ( xref )."
26402601
KCNK2 affects K
| 1
KCNK2 inhibits K. 1 / 1
| 1
reach
"Because all of the identified compounds inhibited K 2P 2.1 (TREK-1)-dependent yeast growth, our discovery of molecules that proved to be activators was unexpected."
23738709
KCNK2 affects HQBM
| 1
KCNK2 activates HQBM. 1 / 1
| 1
reach
"The ones that are most commonly used are : QM/MM methods, the EEF1 solvation model, the replica (molecular replication) methods, the TREK reaction-path facility, the PERT free energy methods, targeted molecular dynamics, the HQBM external perturbation facility, adaptive umbrella sampling, soft core potentials, the Drude oscillator polarizable model, and the VV2 operator splitting velocity Verlet integrator."
19444816
KCNK2 affects Gbetagamma
| 1
KCNK2 binds Gbetagamma. 1 / 1
| 1
reach
"Gbetagamma directly binds to the TREK-1 containing two-pore potassium channel to open the channel."
29731678
KCNK2 affects GNG
| 1
KCNK2 binds GNG. 1 / 1
| 1
reach
"In contrast, GNG5 and GNG10 showed a lack of interaction, and GNG1 and GNG11 showed a weak interaction, indicating that GNG binding to TREK1 is isoform specific.We then asked whether G betagamma can directly open any channels in cultured astrocytes."
23021213
KCNK2 affects G betagamma -induced conductance
| 1
KCNK2 inhibits G betagamma -induced conductance. 1 / 1
| 1
reach
"Compared to the scrambled shRNA, we found that mouse TREK-1-shRNA eliminated the G betagamma -induced conductance (blue trace), which was significantly rescued by coexpression of rat TREK-1 (red trace)."
23021213
KCNK2 affects F_actin
| 1
KCNK2 activates F_actin. 1 / 1
| 1
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"Similarly, TREK-1 overexpression also increased the F-actin content in control cells (XREF_FIG)."
26001192
KCNK2 affects FL-PIP 2
| 1
KCNK2 binds FL-PIP 2. 1 / 1
| 1
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"When directly titrated, the soluble FL-PIP 2 probe bound TREK-1 with a dissociation constant (K d) of 1.6 muM and a Hill slope of 1.35 (XREF_FIG)."
28793254
KCNK2 affects FAS
| 1
KCNK2 inhibits FAS. 1 / 1
| 1
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"In the present study, we showed that decreased expression of TREK-1 in A549 cells caused changes in the cytoskeletal structure, localization of FAs, and an increase in cell deformability."
24586773
KCNK2 affects ERVK-18
| 1
KCNK2 activates ERVK-18. 1 / 1
| 1
reach
"Activation and inhibition of TREK-1 modulates [Ca 2+] TM and lowers the impedance of cell monolayers."
30446509
KCNK2 affects Cell Survival
| 1
KCNK2 activates Cell Survival. 1 / 1
| 1
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"In addition, upregulation of Kcnk2 or knockdown of Foxd3 promoted the cell viability and reduced the apoptosis of the H/R treated PC12 cells."
31959866
KCNK2 affects CHARMM
| 1
KCNK2 activates CHARMM. 1 / 1
| 1
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"The intermediate path points between the saddle points of the converged CPR pathway were further refined using the Synchronous Chain Minimization (SCM) algorithm XREF_BIBR implemented in the TREK module of CHARMM."
19405533
KCNK2 affects CH
| 1
KCNK2 activates CH. 1 / 1
| 1
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"It is not known whether anesthetic modulation of hTREK-1 is accomplished during hypoxic conditions, but the conclusion that TREK-1 activation contributes to CH mediated anesthesia should be viewed with caution."
14996553
KCNK2 affects CAV3
| 1
CAV3 binds KCNK2. 1 / 1
| 1
sparser
"Popdc proteins interact with TREK-1 and Cav3."
24646234
KCNK2 affects BVES/POPDC1
| 1
KCNK2 binds BVES/POPDC1. 1 / 1
| 1
sparser
"TREK-1 is highly expressed in prostate cancer, unlike in healthy prostate or benign prostatic hyperplasia. xref , xref In addition, its expression is strongly correlated with the grade and stage of prostate cancer. xref Overexpression of TREK-1 in healthy prostate epithelial cells increased their proliferation ability. xref In contrast, the knockdown of TREK-1 significantly inhibited the proliferation of prostate cancer cells. xref Recently, an investigation of ion channels and electrogenic proteins in Xenopus oocytes demonstrated that TREK-1 functionally interacts with BVES/POPDC1. xref Co-expression of BVES/ POPDC1 and TREK-1 stimulates a twofold higher current than that measured in the absence of BVES/POPDC1. xref However, the role of BVES/POPDC1–TREK-1 interaction in human cancers has not been examined."
30863095
KCNK2 affects Asp-Gly
| 1
KCNK2 inhibits Asp-Gly. 1 / 1
| 1
sparser
"Interestingly, antidepressant behavior was observed in both acute and chronic depression models with DG neuron-specific TREK-1 inhibition, indicating that the antidepressant effect is sufficient to enhance DG neuron activity alone."
31771312
KCNK2 affects Arg-Ile
| 1
KCNK2 activates Arg-Ile. 1 / 1
| 1
reach
"However, none of these TREK-1 modulators induced noticeable change in astrocyte RI, V M, and the amplitude of passive conductance in WT astrocytes (data not shown)."
26869883
KCNK2 affects ANP
| 1
KCNK2 binds ANP. 1 / 1
| 1
sparser
"Interestingly, also the Popdc protein interaction partner TREK-1 (see below) has been associated with ANP release ( xref )."
26772438
KCNK2 affects AD
| 1
KCNK2 inhibits AD. 1 / 1
| 1
reach
"Previous studies have shown that the blockade or the TREK-1 deletion enhances the midbrain 5-HT neuron firing rate, a key parameter predictive of AD efficacy."
30127743
KCNK10 affects KCNK2, and Mtap2
| 1
KCNK10 binds KCNK2 and Mtap2. 1 / 1
| 1
sparser
"Mtap2 binding to TREK-1 and TREK-2 does not affect directly channel properties but enhances channel surface expression and current density."
18716213
KCN affects KCNK2, and SLC18A2
| 1
KCN binds SLC18A2 and KCNK2. 1 / 1
| 1
sparser
"The complicated interactions between TREK1 potassium channel and monoamine transmitters-receptors were also reviewed and future directions to explore the underline mechanism were also discussed."
23387069
KCN affects KCNK2, and PRNP
| 1
KCN binds KCNK2 and PRNP. 1 / 1
| 1
sparser
"Using a bacterial two-hybrid approach, we identified a novel interaction between PrP(C) and a two-pore potassium channel protein, TREK-1."
16750514
Ischemia affects KCNK2
| 1
Ischemia activates KCNK2. 1 / 1
| 1
sparser
"This action is due to lipidic compounds such as polyunsaturated fatty acid [ xref ] or lysophospholipids [ xref ] which are produced during ischemia that activates TREK and TRAAK channels."
21358977
His-Gly affects KCNK2
| 1
His-Gly activates KCNK2. 1 / 1
| 1
reach
"It is generally agreed that in expression systems Zn 2+ and Hg 2+ enhance the amplitude of TREK1 and TREK2 and strongly decrease the amplitude of the rodent TRESK and TASK3 currents."
24086441
Gq- affects KCNK2
| 1
Gq- inhibits KCNK2. 1 / 1
| 1
reach
"TREK-1 is blocked by the stimulation of both Gq- and Gs coupled membrane receptors."
22022421
Gbetagamma affects KCNK2
| 1
KCNK2 binds Gbetagamma. 1 / 1
| 1
reach
"Gbetagamma directly binds to the TREK-1 containing two-pore potassium channel to open the channel."
29731678
G_protein affects KCNK2
| 1
G_protein activates KCNK2. 1 / 1
| 1
reach
"It has been also reported that paroxetine inhibits G protein activated inwardly rectifying K + channel [XREF_BIBR] and TREK K + channel [XREF_BIBR]."
26807026
G_i affects KCNK2
| 1
G_i activates KCNK2. 1 / 1
| 1
reach
"Gi coupled receptors have been shown to enhance TREK1 current."
22726831
G_alpha affects KCNK2
| 1
G_alpha inhibits KCNK2. 1 / 1
| 1
reach
"TREK1 activity is inhibited by the activation of Galpha q -coupled receptors, such as the thyrotropin releasing hormone receptor 1 (TRHR1) and the Orexin receptor (Orx1R), but is enhanced by the Galpha i -coupled receptors, including the metabotropic glutamate receptor 4 (mGluR4)."
27790056
GRM2 affects KCNK2
| 1
GRM2 activates KCNK2. 1 / 1
| 1
reach
"Stimulation of co-expressed G q -coupled glutamate receptor mGluR1 or the G s -coupled serotonin receptor 5-HT4sR inhibits TREK1 and TREK2 activities, whereas activation of the G i -coupled mGluR2 increases these TREK currents."
12559116
GPI affects KCNK2
| 1
GPI activates KCNK2. 1 / 1
| 1
reach
"First, we found that the permeant ion has a major effect on pHi activation of TREK-1 as reflected in the profound difference in the [H +] required to activate TREK-1 channels in the order Rb +> K +> Tl + (XREF_FIG)."
21822218
GPCR affects KCNK2
| 1
GPCR activates KCNK2. 1 / 1
| 1
sparser
"Previous studies have indicated that both Trek1 and Trek2 can be activated by GPCRs linked to G i/o G proteins (Fink et al., xref ; Patel et al., xref ; Lesage et al., xref ; Murbartian et al., xref ; Deng et al., xref ; Xiao et al., xref ), and both channels are expressed in the mouse midbrain (Lein et al., xref )."
22973213
GNG affects KCNK2
| 1
KCNK2 binds GNG. 1 / 1
| 1
reach
"In contrast, GNG5 and GNG10 showed a lack of interaction, and GNG1 and GNG11 showed a weak interaction, indicating that GNG binding to TREK1 is isoform specific.We then asked whether G betagamma can directly open any channels in cultured astrocytes."
23021213
GLUL affects KCNK2
| 1
GLUL inhibits KCNK2. 1 / 1
| 1
reach
"TREK-1 is blocked by the stimulation of both Gq- and Gs coupled membrane receptors."
22022421
G i -proteins affects KCNK2
| 1
G i -proteins activates KCNK2. 1 / 1
| 1
reach
"57 The requirement of both beta 1 - and beta 2 -adrenoceptors for I Kss inhibition by noradrenaline and the PTX sensitivity of this response suggest that the receptors and G i -proteins modulating TREK like channel activity are co-localized, consistent with the ability of beta 1 -/beta 2 -adrenoceptor subtypes to form heterodimers."
25205295
G betagamma affects KCNK2, and glutamate
| 1
KCNK2 binds G betagamma and glutamate. 1 / 1
| 1
reach
"To answer the question, we considered a possibility that G betagamma directly binds to TREK-1 to open a glutamate permeable channel."
23021213
FOXD3 affects KCNK2
| 1
FOXD3 inhibits KCNK2. 1 / 1
| 1
reach
"The transcription factor Foxd3 induces spinal cord ischemia-reperfusion injury by potentiating microRNA-214-dependent inhibition of Kcnk2."
31959866
FL-PIP 2 affects KCNK2
| 1
KCNK2 binds FL-PIP 2. 1 / 1
| 1
reach
"When directly titrated, the soluble FL-PIP 2 probe bound TREK-1 with a dissociation constant (K d) of 1.6 muM and a Hill slope of 1.35 (XREF_FIG)."
28793254
ENAH affects KCNH1, KCNK2, OBSCN, PTPRC, RGS1, S100A3, and TNR
| 1
S100A3 binds TNR, OBSCN, ENAH, KCNH1, KCNK2, PTPRC, and RGS1. 1 / 1
| 1
sparser
"1q21.1–q44 contains OBSCN , PTPRC , TNR , KCNK2 , S100A3 , ENAH , RGS1 and KCNH1 genes, which were associated with progression of cancer."
20083228
CRH receptors affects KCNK2
| 1
CRH receptors inhibits KCNK2. 1 / 1
| 1
reach
"Activation of the CRH receptors that are coupled to the adenylate cyclase pathway suppressed the activation of TREK-1 current by AA and reversed the AA mediated hyperpolarization."
21343252
CRH affects KCNK2
| 1
CRH inhibits KCNK2. 1 / 1
| 1
reach
"Activation of the CRH receptors that are coupled to the adenylate cyclase pathway suppressed the activation of TREK-1 current by AA and reversed the AA mediated hyperpolarization."
21343252
CCL2 affects CEL, IL6, and KCNK2
| 1
CEL binds IL6, KCNK2, and CCL2. 1 / 1
| 1
sparser
"Interestingly, the decrease in BAL fluid IL-6 and MCP-1 levels was associated with increased cellular apoptosis in TREK-1 deficient mice exposed to HO+MV."
25126877
CBX4 affects KCNK2
| 1
Mutated CBX4 inhibits KCNK2. 1 / 1
| 1
reach
"A possible mechanism for TREK and TRAAK inhibition by PC2 mutation may involve an effect on the biosynthesis and/or trafficking of the TREK and TRAAK channels."
22832196
CAV3 affects KCNK2
| 1
CAV3 binds KCNK2. 1 / 1
| 1
sparser
"Popdc proteins interact with TREK-1 and Cav3."
24646234
C10orf90 affects KCNK2
| 1
C10orf90 activates KCNK2. 1 / 1
| 1
reach
"In addition, TREK-1, TREK-2, TRAAK and THIK-1 are stimulated by internally applied arachidonic acid and polyunsaturated fats [19,22,25-27]."
12421546
BVES/POPDC1 affects KCNK2
| 1
KCNK2 binds BVES/POPDC1. 1 / 1
| 1
sparser
"TREK-1 is highly expressed in prostate cancer, unlike in healthy prostate or benign prostatic hyperplasia. xref , xref In addition, its expression is strongly correlated with the grade and stage of prostate cancer. xref Overexpression of TREK-1 in healthy prostate epithelial cells increased their proliferation ability. xref In contrast, the knockdown of TREK-1 significantly inhibited the proliferation of prostate cancer cells. xref Recently, an investigation of ion channels and electrogenic proteins in Xenopus oocytes demonstrated that TREK-1 functionally interacts with BVES/POPDC1. xref Co-expression of BVES/ POPDC1 and TREK-1 stimulates a twofold higher current than that measured in the absence of BVES/POPDC1. xref However, the role of BVES/POPDC1–TREK-1 interaction in human cancers has not been examined."
30863095
AristA affects KCNK2
| 1
AristA activates KCNK2. 1 / 1
| 1
reach
"AristA enhances TREK-1 and TREK-2 channel currents."
26914156
Altered beta 1 -adrenoreceptor affects KCNK2
| 1
Altered beta 1 -adrenoreceptor activates KCNK2-I267T. 1 / 1
| 1
reach
"Altered beta 1 -adrenoreceptor modulation in TREK-1 I267T channels."
28242754
Akap5 affects COPB1, KCNK2, and Mtap2
| 1
COPB1 binds KCNK2, Akap5, and Mtap2. 1 / 1
| 1
sparser
"Also, bindings of AKAP150 (A-Kinase-Anchoring Protein), Mtap2 (Microtubule-Associated Protein 2) and β-COP (Coat Protein Complex) to TREK channels enhance surface expression [19] ."
28676394
ANXA2 affects COCH, and KCNK2
| 1
COCH binds ANXA2 and KCNK2. 1 / 1
| 1
sparser
"Cochlin interacts with TREK-1 and annexin A2."
21886777
ANP affects KCNK2
| 1
KCNK2 binds ANP. 1 / 1
| 1
sparser
"Interestingly, also the Popdc protein interaction partner TREK-1 (see below) has been associated with ANP release ( xref )."
26772438
8-Br-cGMP affects KCNK2
| 1
8-Br-cGMP activates KCNK2. 1 / 1
| 1
reach
"Sodium nitroprusside (10 (-6) or 10 (-5) m) and 8-Br-cGMP (10 (-4) or 10 (-3) m) increased TREK-1 currents in perforated whole cell and single channel recordings."
11560940
5-HT4 receptors affects KCNK2
| 1
5-HT4 receptors activates KCNK2. 1 / 1
| 1
reach
"Among the few receptor subtypes known to modulate TREK-1, the stimulation of 5-HT4 receptors and the blockade of mGluR2/3 ones both activated 5-HT impulse flow, effects also suppressed by mPFC lesion."
25233810
2-aminoethoxydiphenylborane affects KCNK2
| 1 1
2-aminoethoxydiphenylborane activates KCNK2. 1 / 1
| 1 1
reach
"2-APB ACTIVATES ALL MEMBERS OF THE TREK SUBFAMILY."
23720627
2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine affects KCNK2
| 1
2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine inhibits KCNK2. 1 / 1
| 1
reach
"We demonstrate that lysophospholipids (LPs) and platelet activating factor also produce large specific and reversible activations of TREK-1 and TRAAK."
10744694
17beta-estradiol affects KCNK2
| 1
17beta-estradiol activates KCNK2. 1 / 1
| 1
reach
"17beta-estradiol potentiates TREK1 channel activity through G protein coupled estrogen receptor."
29883692
1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile affects KCNK2
| 1
1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile inhibits KCNK2. 1 / 1
| 1
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"Application of 10 muM fluoxetine, 20 muM paroxetine, 100 muM citalopram, and 30 muM chlorpromazine significantly inhibited TREK-1 currents by 28 +/- 11%, 40 +/- 9%, 31 +/- 10%, and 52 +/- 10%, respectively (p < 0.05, XREF_FIG a-c)."
29156592
1-NBP affects KCNK2
| 1
1-NBP inhibits KCNK2. 1 / 1
| 1
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"1-NBP potently inhibited TREK-1 current and elevated the membrane potential, which may contribute to its neuroprotective activity."
21293470
(2-hydroxyphenyl)acetic acid affects KCNK2
| 1
(2-hydroxyphenyl)acetic acid inhibits KCNK2. 1 / 1
| 1
reach
"In particular, OHP infusion was found to downregulate potassium channels TREK1, TRAAK, and upregulate hyperpolarization activated HCN1 channels, TRPA1, and Na v 1.8 in DRG."
29051466