IndraLab
Statements
Calcium(2+) activates KCNMA1. 145 / 162
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"KCNMA1 encodes for the alpha subunit of the large conductance calcium-activated potassium channel (BK channel; also known as Slo), and its alternative splicing has been suggested to be important for frequency tuning along the tonotopic axis by influencing the channel gating properties (Navaratnam et al., 1997; Rosenblatt et al., 1997; Frucht et al., 2011)."
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"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."
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"Slo1 channels are activated by increases in Ca 2+ nearby Ca 2+ -recognition sites in the slo1 cytosolic tail: one high-affinity and one low-affinity sites locate to the Regulator of Conductance for K + (RCK) 1 domain, while another high-affinity site locates within the RCK2 domain."
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"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."
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"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]."
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"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."
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"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."
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"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."
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"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."
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"The identity of the specific potassium channels involved seems to be very cell type specific and indeed both Ca activated K channels (KCNMA) (Garcia et al., 1991) and KV1.3 (KCNA3) channels (Garcia-Calvo et al., 1993) have been separately identified on the basis of toxin inhibition (charybdotoxin and margatoxin, respectively)."
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"Knockdown of JPH2 expression had no effect on SR Ca store load or Ca uptake, the frequency of spontaneous Ca sparks, or the amplitude and kinetics of individual events, but nearly eliminated transient BK channel currents activated by Ca sparks, demonstrating that JPH2 is necessary for functional coupling of BK channels on the plasma membrane and RyR2s on the SR."
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"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."
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"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."
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"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."
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"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+."
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"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."
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"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."
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"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."
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"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."
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"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."
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"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."
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"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."