"Calcium sparks, a highly localized calcium transients originating at the triad, are mediated by ryanodine receptors and L-type Ca 2+ channels and cause BK channel activation, which is responsible for muscle inactivation."
"Therefore, BK channel itself did not generate [Ca 2+] i oscillation but was modulated by [Ca 2+] i oscillations.In this study, we demonstrated [Ca 2+] i dynamics in isolated single human mesenchymal stem cell and examined the mechanisms and functions of spontaneous [Ca 2+] i oscillations."
"The Slo1 channel is activated by both voltage and intracellular Ca 2+ while the IK and SK channels are gated by intracellular Ca 2+ alone."
"The gene that was up-regulated, Kcnmb1 (Calcium activated potassium channel subunit beta-1), is a regulatory subunit of the calcium activated potassium KCNMA1 channel, controlling both the sensitivity and gating kinetics of this channel."
"This meant in some cells, the TRPV1 channels might be degraded or destroyed by enzymes during preparation, BK channel could not be activated by the absence of calcium influx."
"We have shown that BK channel activation, driven by Ca 2+ influx at single synaptic terminals, serves to constrain the AP broadening occurring during spike trains."
"A major determinant of its anthelmintic effect is the calcium activated potassium channel SLO-1."
"Comparisons of the BK channel structures in the absence and presence of Ca 2+ indicate that the gating ring expands in response to Ca 2+ binding and propagates conformational changes to the channel pore XREF_BIBR, XREF_BIBR, suggesting a likely involvement of the interfaces between the RCK domains of adjacent subunits, known as the " intersubunit assembly interface " XREF_BIBR, XREF_BIBR, in BK channel activation by Ca 2+."
"Elevation of intra-cellular Ca 2+ from the sarcoplasmic reticulum opens L-type Ca 2+ channels (LTCCs); in turn this increased calcium level activates MaxiK channels leading to relaxation."
"The latter response denotes that basal Ca 2+ concentrations promote BK channel potentiation, whereas high concentrations (> 10 muM) induce inhibition."
"Interestingly, thalidomide elevated big- or large-conductance, calcium activated K + (BK) channel expression in the plasma membrane and BK channel activity in the hippocampus."
"The large-conductance voltage- and calcium activated human Slo1 BK Ca channel is a critical member of the high-conductance Slo family of K + channel XREF_BIBR - XREF_BIBR."
"Since slo-2 encodes the only other calcium activated SLO like potassium channel in C. elegans and its expression overlaps with slo-1 [XREF_BIBR, XREF_BIBR, XREF_BIBR], we hypothesized that slo-1 and slo-2 may function redundantly to control AWC asymmetry."
"Large conductance calcium- and voltage dependent BK potassium channels (aka BK Ca, MaxiK, Slo1, KCa1.1, and KCNMA1) are expressed in a wide variety of tissues throughout the body and are activated by both intracellular Ca 2+ and membrane depolarization."
"In MVN cells Cav3 calcium influx activated KCa1.1 current from as low as -70 mV for ramp stimuli as well as during square wave steps from -100 mV to +40 mV, and that these were sensitive to block by low concentrations of mibefradil or Ni 2+."
"The BK channel can be activated by intracellular Ca (2+) and Mg (2+), as well as by membrane depolarization."
"The voltage gated L-type calcium channel and the functionally linked calcium activated BK channel represent a functional dyad."
"The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium activated potassium channel Slo-1."
"Charybdotoxin is known to block calcium activated K Ca1.1, MaxiK or BK channels XREF_BIBR, K Ca3.1 or intermediate channels XREF_BIBR and voltage dependent K v1.3 shaker current XREF_BIBR."
"During muscarinic signaling, BK channels assume a greater role due to the depolarized membrane potential and elevated calcium that support BK channel activation."
"Increases in intracellular Ca 2+ caused by A23187 shift the voltage-dependence of BK channel activation to more negative potentials and thus allow channel opening at the resting membrane potential."
"Ca 2+ activates the BK channel SLO-1, which truncates the rise in membrane potential, preventing activation of the L-type voltage gated calcium channel EGL-19."
"Binding of the intracellular Ca 2+ at the CTD enhances the BK channel opening."
"In tsA-201 cells a single pulse from -100 mV to +40 mV recruited very little KCa1.1 current while in MVN cells a step of this size consistently recruited sufficient Cav3 calcium current to activate KCa1.1 channels."
"LRRC26 knockdown did not alter Ca 2+ sparks, but reduced BK channel voltage-sensitivity, which reduced channel apparent Ca 2+ -sensitivity and transient BK current frequency and amplitude in myocytes."
"Since SLO-1 colocalizes with the L-type voltage gated Ca 2+ channel EGL-19 and EGL-19 is the predominant voltage gated Ca 2+ channel in body-wall muscle, SLO-1 could potentially be activated by Ca 2+ entering through EGL-19 and, in turn, regulate intracellular [Ca 2+]."
"Large conductance BK-type K channels (Slo1) are activated by voltage and intracellular Ca 2+, play an important role in synaptic physiology, and are present in parts of the brain that contain synaptic Cu 2+ and Zn 2+."
"The guanylate kinase domain of Ca (v) beta1 mediates Slo1 regulation through its binding to calcium bowl domains, and this domain of Ca (v) beta1 is necessary and sufficient for the observed effects on BK (Ca) activation."
"The distributions of open and shut times were calculated to further examine the difference in the gating of the BK channel activated by Ca 2+ and Sr 2+."
"This process involves stimulation of calcium activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct."
"We then used patch clamp recordings in in vitro tissue slices from P12-P16 rats to examine if Cav3 calcium influx is sufficient to activate KCa1.1 in MVN cells."
"In the vasculature, the most important K+ channel subclasses that are involved in the action of various endothelium derived relaxing factors are the ATP sensitive KATP channel and the large conductance calcium activated BK channel."
"Other members of this gene family include BK (Slo1) channels, which are activated by cytosolic Ca 2+ instead of Na +, as well as a host of orthologues found in prokaryotes, such as MthK (Rothberg & Magleby, 2000; Jiang etal."
"The properties of the large-conductance K channel are consistent with its identification as a calcium activated maxi K channel described in a variety of tissues."
"Apical Kcnma1 is activated by Ca 2+ XREF_BIBR."
"For both inside-out and outside-out configurations, Slo1 channels were activated by 300 muM cytosolic Ca 2+ at pH 8.5, while MC13 channels were activated with pH 8.5 with no Ca 2+."
"However, the beta2ND subunit has different effects on the Ca 2+ dependent activation of the two Slo1 orthologs."
"Furthermore, a transient Ca 2+ entry through Cav3.2 channels is able to induce a persistent BK channel activation."
"A series of compounds have been reported which open the large conductance calcium activated potassium channel (maxi-K)."
"Emodepside exerts its nematicidal effects mainly through its validated target, the tetrameric voltage- and calcium activated potassium channel SLO-1."
"Large-conductance calcium activated (maxi-K, BK) potassium channels are widely distributed in the brain."
"But several lines of evidences indicate that potassium large conductance calcium activated channel, known as BK channel, is likely to be included."
"Third, the BK channel can be independently activated by Ca 2+ or voltage, and it can open in the absence of Ca 2+."
"Lolitrem B potently inhibited hSlo potassium currents activated by depolarising voltage pulses in the presence of 10 microM free calcium."
"Despite the functional simplicity of the BK channel, which is activated principally (for the purpose of this Commentary) by cytoplasmic Ca 2+ and depolarization, and our high level of understanding of the mechanisms underlying its activation, there are still many intricacies of this channel that are not well understood."
"Voltage- and Ca 2+ -dependent activation of Slo1 was negatively correlated with the C-linker length."
"When cells that have been permeabilized with streptolysin-O (SLO) were treated with either 10 muM Ca 2+ / 3 mM ATP or < = 100 muM GTPgammaS/1 mM ATP and cytosol (from rat brain) -- conditions that induced compound exocytosis, we observed that SNAP-23 relocated from its foci both along the plasma membrane and into the interior of the cell where it associated with secretory granules (Guo et al., 1998)."
"Maxi-K channel opening stimulated by Ca 2+ and the pharmacological opener would function to limit further Ca 2+ entry by hyperpolarizing neurons, thereby reducing voltage dependent calcium entry points via some Ca 2+ channels and possibly NMDA receptors."
"This is consistent with Ca 2+ entry through L-type Ca 2+ channels driving BK channel activation and hyperpolarization of the membrane potential."
"In sympathetic neurons of rat superior cervical ganglia, blocking either BK channels with charybdotoxin or L-type Ca 2+ channels with nifedipine increases the half-width of action potentials whereas blocking other VSCCs has no such effect, suggesting that Ca 2+ entry via L-type channels selectively activates the BK channel [XREF_BIBR]."
"Activation of Slo1 by Ca 2+ Is Potentiated by Internal Mg 2+."
"Here, we show that voltage- and calcium activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation."
"To determine what proportion of the non inactivating outward current is carried by SLO potassium currents, we examined the effect of extracellular Ca 2+ on outward currents in dilp2-neurons, since the SLO channel is highly activated by intracellular Ca 2+ that enters through Ca 2+ channels."
"It is clear that the aminophenylamidines are agonists of acetylcholine receptors and have a very similar mode of action as levamisole XREF_BIBR, XREF_BIBR whereas several targets have been suggested for the cyclooctadepsipeptides with the voltage gated, calcium activated potassium channel SLO-1 as most important candidate XREF_BIBR, XREF_BIBR, XREF_BIBR."
"Thus, SloTx is a more reliable pharmacological tool than ChTx or IbTx to distinguish channels formed by MaxiK alpha+ beta4 complexes.The toxin specificity was assayed in different types of K + channels such as the voltage dependent ShIR (Shaker K + channel with inactivation removed), Kv1.1, and Herg; the voltage- and calcium activated hSlo and dSlo; the voltage-independent and calcium-activated SK1, SK2 and SK3; and the voltage independent IRK2.1."
"Interestingly, the large Ca (2+) activated potassium channel (BKalpha, or KCNMA1) was very highly expressed in all chondrocytes examined."
"18,19 Maxi-K channel opening stimulated by Ca 2+ in the presence of a pharmacological opener would act to limit further Ca 2+ entry, thus interrupting the potentially fatal neurotoxic cascade initiated by abnormally high Ca 2+ entry, a circumstance encountered during neuronal ischemia."
"This ATPase is potentially responsible for the difference in the observed higher level of the cytosolic Ca 2+ increase after calcium ionophore stimulation in SLO treated iRBC than that in saponin treated iRBC."
"In contrast, for channels in which the D362 and D367 site alone is mutated, increases in [Ca 2+] from 0 to 300 muM produce only a small slowing of deactivation in marked contrast to wild-type Slo1 (compare XREF_FIG A with XREF_FIG C)."
"Together these results confirm that Cav3 mediated calcium influx can activate KCa1.1 current in the low voltage range of ~ -50 mV, well below that of most voltage gated potassium channels that activate above -40 mV XREF_BIBR."
"FMRP was also shown to interact with the auxiliary beta4 subunit of the calcium activated potassium (BK) channel; this interaction increases calcium dependent activation of the BK channel."
"The Slack and Slo channels have intermediate conductances of about 60-180 pS and are activated by cytoplasmic calcium."
"However, Ca ++ increase in the context of strong depolarization triggered by ATP may activate KCa1.1."
"Previous studies have shown that MaxiK channels are activated by the release of Ca 2+ from sarcoplasmic reticulum (SR) stores."
"LRRC26 knockdown did not alter Ca (2+) sparks but reduced BK channel voltage sensitivity, which decreased channel apparent Ca (2+) sensitivity and transient BK current frequency and amplitude in myocytes."
"Interestingly, the apparent Hill coefficient for inhibition by proton appears to be only slightly voltage dependent, (XREF_FIG), in contrast to the voltage dependence for activation of Slo1 by Ca 2+ or Mg 2+."
"The obtained results indicated that intracellular Ca ++ chelation with BAPTA abolished the inhibitory effect of BK channel activation on RD.."
"These results indicate that the voltage dependence of a BK channel activated by Ca 2+ is indistinguishable from that activated by Sr 2+ as long as equipotent concentrations of Ca 2+ and Sr 2+ are used to activate the channel to a similar degree."
"Maxi-K + channels of both, HO-2 +/+ and -/- glomus cells, were modulated by intracellular Ca 2+ (XREF_FIG), and single-channel current amplitude and slope single-channel conductance were similar in the two animal types (XREF_FIG)."
"Hence, increase in the membrane potential or intracellular Ca 2+ concentration can trigger the opening of the BK channel by mediating transient K + outward current in a negative regulatory manner."
"BK channel is activated by increased Ca 2+ spike released by ryanodine receptors, presents on smooth endoplasmic reticulum in SMC."
"CRBN is a substrate receptor for the Cul4A and B-DDB 1 ubiquitin ligase (CRL4) and can target voltage- and calcium activated BK channel for ER retention."
"In fact, it has been previously observed that the functional disruption of the calcium bowl does not disrupt BK channel regulation produced by Cd 2+, leading to the suggestion that the BK channel may contain additional Ca 2+ regulatory sites."
"Among the diverse family of K + channels, large-conductance, calcium activated K + (Maxi-K, also known as BK Ca) channels are the predominant K + channels in myometrium, and thus have been implicated in the control of cellular excitability [XREF_BIBR]."
"The large-conductance calcium activated potassium channel KCa1.1 (BKCa, maxi-K) influences aqueous humor outflow facility, but the contribution of auxiliary beta-subunits to KCa1.1 activity in the outflow pathway is unknown."
"PiMA (1) opens the voltage gated Shaker K channel (though to a lower extent than PUFAs) XREF_BIBR, as well as the Ca activated BK channel XREF_BIBR."
"While both compounds exerted practically no effect on the neuronal Nav1.2 and the skeletal muscle Nav1.4 channel or Kv channels from the Kv4, Kv7, Kv11, or KCa2 (SK) family, they exhibited only moderate selectivity over Kv1, Kv2, Kv3 family channels, Kv11.1 (hERG), and the calcium activated K + channels KCa1.1 and KCa3.1."
"BK channel activation can be induced by Ca 2+ influx through L-type channels, P/Q-type channels, N-type channels, and NMDAR but not R-type Ca v 2.3 Ca 2+ channels."
"We also speculate that potassium channels with inherent noisy current with PSDs following a distribution in the relevant frequency range, underlie the observed high-frequency power laws, and the slow voltage- and calcium activated BK channel, reported to have a very large channel conductance XREF_BIBR, is suggested as a main contributor XREF_BIBR."
"We further show that flow stimulated Ca 2+ influx through TRPV5 and TRPV6 is sufficient to activate Slo1 encoded Ca 2+ -activated maxi-K, which are present in DCT2 and CNT where flow stimulated K + secretion is known to take place [XREF_BIBR]."
"It has often been reported that Ca 2+ and Mg 2+ not only activate MaxiK channels but also block at millimolar concentrations."
"BK channel has large single-channel conductance (often> 200 pS), and is activated by membrane depolarization and elevation of cytoplasmic free [Ca 2+]."
"For example,> 500 isoforms of the calcium activated potassium channel Slo that are translated from the different mRNAs produced by the alternative splicing of a single slo gene define the ability of ears to detect a remarkable range of frequencies."
"XREF_BIBR A syndrome of generalised epilepsy with paroxysmal movement disorders has been shown to be caused in one kindred by a dominant missense mutation in the calcium activated potassium channel gene KCNMA1."
"These [Ca 2+] i oscillations modulated the activities of a 170 pS Ca 2+ -activated K + channel, which produced the fluctuation of membrane potential."
"Considering that [Ca (2+)] (i), which would activate the BK channel, is the key issue in neurodegeneration, it would be suggested by the results from this study that K (+) channel blocker, rather than activator, would potentially present the neuronal protective effect."
"We analyzed transcript levels in the dataset; the acid sensing potassium channel (TASK-2), epithelial sodium channel (ENaC) and Ca 2+ activated chloride channel were all decreased (anoctamin-1, TMEM16), whereas Ca 2+ activated potassium channels (KCa3.1, " SK " and KCa1.1, " BK ") and aquaporin 1 (AQP1) were strongly up-regulated."
"The diversity of Ca 2+ channels that may mediate BK channel activation suggests that activation of BK channels by colocalized Ca 2+ channels is not a unique property of a specific type of VSCC; rather, the apparent specificity of coupling reflects the identity of VSCCs that are coexpressed and colocalized with the BK channel."
"In rat cerebellar Purkinje neurons, blocking P/Q-type Ca 2+ channels suppresses afterhyperpolarization [XREF_BIBR], which is mainly contributed by the BK channel [XREF_BIBR], suggesting that Ca 2+ entry via P/Q-type channels may activate the BK channel."
"Several calcium sources could potentially regulate BK channel activity."
"Removal of extracellular Ca 2+, the influx of which is required to activate Slo, resulted in a similar reduction (36%; 55.8 +/- 3.2 pA/pF), consistent with ChTX blocking only the Slo mediated component of I Kfast (data not shown)."
"These genes encode a BK calcium activated potassium channel SLO-1 and an NPQR-type voltage gated calcium channel UNC-2 and UNC-36."
"To further test whether calcium influx through Cav3.2 channels could provide a sufficient increase of [Ca] i to mediate a shift in KCa1.1 voltage dependence, cells were held at -100 mV and stepped to voltages ranging from -70 to +40 mV in the presence or absence of coexpressed Cav3.2 channels."
"We found that the interdomain interactions between these two positions not only alter the local conformations near the Mg (2+)-binding site but also change distant conformations including the pore-gate domain, thereby affecting the voltage- and Ca (2+)-dependent activation of the BK channel."
"A maxi K channel with a single-channel conductance of 132 pS (105 mM K on both sides of the membrane, 15 degrees C) is activated both by micromolar concentrations of internal Ca and by depolarization."
"However, given the data we present in this report (especially XREF_FIG and XREF_FIG), the calcium concentrations in ischemic neurons should be sufficient to allow a strong potentiation of BK channel activity in CNS neurons and hyperpolarization of the ischemic neurons, reducing excitatory amino acid release, and reducing ischemic calcium entry."
"The biophysical mechanism of BK channel activation by voltage and Ca 2+ can be described by a well established allosteric gating model, in which the channel pore opening is allosterically regulated by the movement of each voltage sensor and the binding of Ca 2+ at each Ca 2+ sensor on the four subunits in a largely independent manner XREF_BIBR, XREF_BIBR."
"Together the results identify a novel Cav3-KCa1.1 signaling complex where Cav3 mediated calcium entry enables KCa1.1 activation over a wide range of membrane potentials according to the unique voltage profile of Cav3 calcium channels, greatly extending the roles for KCa1.1 potassium channels in controlling membrane excitability."
"Previous work indicates that specific isoforms of HVA calcium channels can activate KCa1.1 channels to contribute to spike repolarization and generating AHPs XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR."
"Voltage- and calcium activated SLO-1 and SLO-2 BK potassium channels act redundantly downstream of NSY-5 to antagonize calcium channel mediated signaling in promoting the AWC ON subtype [XREF_BIBR]."
"When the Ca 2+ bowl is deleted, the BK channel is still activated by Ca 2+ but with lower affinity."
"Therefore, we have quantified the mRNA expression of the large-conductance calcium activated potassium channel gene MaxiK XREF_BIBR."
"Since the Ca 2+ or voltage sensor for BK channel activation can act relatively independently to each other XREF_BIBR, XREF_BIBR, it is thus implied that the activation conformation of BK channel induced by variant cytoplasmic Ca 2+ concentrations may be different."
"Therefore, calcium entry through a single Cav3 calcium channel is insufficient to activate KCa1.1 even though the two proteins are in close proximity."
"BK channel activation by Ca 2+ sparks triggers transient BK currents (TBKCs), also known as spontaneous transient outward currents (STOCs) [XREF_BIBR], which regulate UBSM excitability."
"For example, Slo1 BK channels are allosterically activated by both intracellular Ca 2+ and membrane depolarization."
"We speculate that activation of the maxi K +-channels caused by an increased intracellular Ca t +-concentration during the process of bone resorption, may inactivate resorption activity."
"BK channel activity is initiated by depolarization and enhanced by the simultaneous increase in free intracellular calcium (Ca 2+) concentration."
"Kcnma1, also known as the BK Ca channel, is activated by both elevated [Ca 2+] i and membrane depolarization."
"Focal adhesion kinase pp125FAK interacts with the large conductance calcium activated hSlo potassium channel in human osteoblasts : potential role in mechanotransduction."
"The large-conductance Ca 2+ - and voltage activated K + (MaxiK, BK, BK Ca, Slo1, K Ca 1.1) channel role in cell signalling is becoming apparent as we learn how the channel interacts with a multiplicity of proteins not only at the plasma membrane but in intracellular organelles including the endoplasmic reticulum, nucleus and mitochondria."
"We hypothesized that in M4, Ca 2+ that enters through UNC-2 and UNC-36 activates SLO-1, thereby truncating neuronal depolarization and inhibiting vesicle fusion."
"A recent report also shows that a non selective cation channel activated by [Ca 2+] i produces the membrane depolarization to reduce Ca 2+ entry through I SOCs [34,36]."
"The Slo1 alpha channel activation by Ca 2+ becomes observable at> = ~ 100 nM Ca 2+ (Cui et al., 1997; Jan and Jan, 1997)."
"Cell membrane voltage and intracellular Ca 2+ activate Slo1 synergistically, making it a central regulator of various physiological processes that couple electrical signaling to Ca 2+ -mediated events such as muscle contraction, hormone secretion, and neuronal excitability XREF_BIBR, XREF_BIBR."
"Maxi-K, which has a large conductance, has a low open probability at baseline, but can be activated by increases in intracellular Ca 2+ and membrane depolarization [XREF_BIBR]."
"Specific primers for QRT-PCR for MR (nuclear receptor subfamily 3, group C, member 2; Nr3c2), BKCaalpha1 (potassium large conductance calcium activated channel, subfamily M, alpha member 1; Kcnma1), BKCabeta1 (potassium large conductance calcium activated channel, subfamily M, beta member 1; Kcnmb1), Cav1.2 (calcium channel, voltage dependent, L type, alpha 1C subunit; Cacna1c) and B2m are listed in XREF_SUPPLEMENTARY."
"Using a ramp command over a -100 to -30 mV range with paxilline or mibefradil treatment further revealed LVA outward current that activated just subsequent to LVA inward calcium current, indicating that Cav3 calcium influx can activate KCa1.1 above ~-70mV."
"We further examined the time course of KCa1.1 activation by Cav3.2-mediated calcium influx by increasing the amount of time between the Cav3.2 prepulse to -30 mV and the P2 step."
"Thus, at positive membrane potential, the activation of the BK channel caused by ATP was sufficient to counterbalance the inhibition of the BK channel caused by the chelation of free calcium by ATP; at negative membrane potential, however, the effect of ATP on P open was more inhibitory than would be expected, even bearing in mind the chelation of free calcium by ATP."
"In this study we test the hypothesis that the steroid hormone ecdysone regulates gene expression of the voltage gated calcium activated potassium ion channel, Slowpoke or KCNMA1."
"The calcium influx required to activate KCa1.1 channels can derive from high voltage activated (HVA) calcium channel conductance by virtue of a molecular association between KCa1.1 and HVA calcium channels XREF_BIBR, XREF_BIBR - XREF_BIBR."
"Having determined that ChTX diminishes ischemia induced depression of fEPSPs, we asked if BK channel activation is caused by the increased [Ca 2+] i that occurs during OGD."
"The same results were observed in SLO permeabilized sperm, where exocytosis was directly triggered by a free calcium rise in the incubation medium (Figs. 1 D-E)."
"XREF_BIBR, XREF_BIBR We also compare Slo3 pharmacological sensitivity to that of its closely related homologue, the Ca 2+ - and voltage activated Slo1 (or BK-type) K + channel."