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Proc Natl Acad Sci U S A
2020 Jun 23;11725:14512-14521. doi: 10.1073/pnas.1908183117.
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Coupling of Ca2+ and voltage activation in BK channels through the αB helix/voltage sensor interface.
Geng Y
,
Deng Z
,
Zhang G
,
Budelli G
,
Butler A
,
Yuan P
,
Cui J
,
Salkoff L
,
Magleby KL
.
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Large-conductance Ca2+ and voltage-activated K+ (BK) channels control membrane excitability in many cell types. BK channels are tetrameric. Each subunit is composed of a voltage sensor domain (VSD), a central pore-gate domain, and a large cytoplasmic domain (CTD) that contains the Ca2+ sensors. While it is known that BK channels are activated by voltage and Ca2+, and that voltage and Ca2+ activations interact, less is known about the mechanisms involved. We explore here these mechanisms by examining the gating contribution of an interface formed between the VSDs and the αB helices located at the top of the CTDs. Proline mutations in the αB helix greatly decreased voltage activation while having negligible effects on gating currents. Analysis with the Horrigan, Cui, and Aldrich model indicated a decreased coupling between voltage sensors and pore gate. Proline mutations decreased Ca2+ activation for both Ca2+ bowl and RCK1 Ca2+ sites, suggesting that both high-affinity Ca2+ sites transduce their effect, at least in part, through the αB helix. Mg2+ activation also decreased. The crystal structure of the CTD with proline mutation L390P showed a flattening of the first helical turn in the αB helix compared to wild type, without other notable differences in the CTD, indicating that structural changes from the mutation were confined to the αB helix. These findings indicate that an intact αB helix/VSD interface is required for effective coupling of Ca2+ binding and voltage depolarization to pore opening and that shared Ca2+ and voltage transduction pathways involving the αB helix may be involved.
Bao,
Elimination of the BK(Ca) channel's high-affinity Ca(2+) sensitivity.
2002, Pubmed,
Xenbase
Bao,
Elimination of the BK(Ca) channel's high-affinity Ca(2+) sensitivity.
2002,
Pubmed
,
Xenbase
Barrett,
Properties of single calcium-activated potassium channels in cultured rat muscle.
1982,
Pubmed
Brenner,
Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.
2000,
Pubmed
Budelli,
Properties of Slo1 K+ channels with and without the gating ring.
2013,
Pubmed
,
Xenbase
Butler,
mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.
1993,
Pubmed
,
Xenbase
Chen,
BK channel opening involves side-chain reorientation of multiple deep-pore residues.
2014,
Pubmed
Cui,
Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca-activated K+ channels.
1997,
Pubmed
,
Xenbase
Geng,
Single-channel kinetics of BK (Slo1) channels.
2014,
Pubmed
Gu,
BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells.
2007,
Pubmed
Guan,
Allosteric-activation mechanism of BK channel gating ring triggered by calcium ions.
2017,
Pubmed
Hite,
Structural basis for gating the high-conductance Ca2+-activated K+ channel.
2017,
Pubmed
Holtzclaw,
Role of BK channels in hypertension and potassium secretion.
2011,
Pubmed
Horrigan,
Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels.
2002,
Pubmed
,
Xenbase
Horrigan,
Allosteric voltage gating of potassium channels I. Mslo ionic currents in the absence of Ca(2+).
1999,
Pubmed
,
Xenbase
Hoshi,
Transduction of voltage and Ca2+ signals by Slo1 BK channels.
2013,
Pubmed
Hu,
Effects of multiple metal binding sites on calcium and magnesium-dependent activation of BK channels.
2006,
Pubmed
,
Xenbase
Jia,
Hydrophobic gating in BK channels.
2018,
Pubmed
Jiao,
Genome wide association study identifies KCNMA1 contributing to human obesity.
2011,
Pubmed
Koval,
A role for the S0 transmembrane segment in voltage-dependent gating of BK channels.
2007,
Pubmed
Krishnamoorthy,
The NH2 terminus of RCK1 domain regulates Ca2+-dependent BK(Ca) channel gating.
2005,
Pubmed
,
Xenbase
Kshatri,
Functional validation of Ca2+-binding residues from the crystal structure of the BK ion channel.
2018,
Pubmed
Latorre,
Molecular Determinants of BK Channel Functional Diversity and Functioning.
2017,
Pubmed
Lee,
Modulation of BK channel gating by the ß2 subunit involves both membrane-spanning and cytoplasmic domains of Slo1.
2010,
Pubmed
,
Xenbase
Lee,
BK channel activation: structural and functional insights.
2010,
Pubmed
Li,
Molecular determinants of Ca2+ sensitivity at the intersubunit interface of the BK channel gating ring.
2018,
Pubmed
Lorenzo-Ceballos,
Calcium-driven regulation of voltage-sensing domains in BK channels.
2019,
Pubmed
,
Xenbase
Ma,
Role of charged residues in the S1-S4 voltage sensor of BK channels.
2006,
Pubmed
,
Xenbase
Miranda,
Voltage-dependent dynamics of the BK channel cytosolic gating ring are coupled to the membrane-embedded voltage sensor.
2018,
Pubmed
,
Xenbase
Moczydlowski,
Gating kinetics of Ca2+-activated K+ channels from rat muscle incorporated into planar lipid bilayers. Evidence for two voltage-dependent Ca2+ binding reactions.
1983,
Pubmed
Niu,
Linker-gating ring complex as passive spring and Ca(2+)-dependent machine for a voltage- and Ca(2+)-activated potassium channel.
2004,
Pubmed
,
Xenbase
Pantazis,
Biophysics of BK Channel Gating.
2016,
Pubmed
Robitaille,
Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release.
1993,
Pubmed
Rothberg,
Voltage and Ca2+ activation of single large-conductance Ca2+-activated K+ channels described by a two-tiered allosteric gating mechanism.
2000,
Pubmed
Savalli,
The contribution of RCK domains to human BK channel allosteric activation.
2012,
Pubmed
Schreiber,
A novel calcium-sensing domain in the BK channel.
1997,
Pubmed
,
Xenbase
Shi,
Intracellular Mg(2+) enhances the function of BK-type Ca(2+)-activated K(+) channels.
2001,
Pubmed
,
Xenbase
Shi,
Mechanism of magnesium activation of calcium-activated potassium channels.
2002,
Pubmed
Sweet,
Measurements of the BKCa channel's high-affinity Ca2+ binding constants: effects of membrane voltage.
2008,
Pubmed
Tao,
Molecular structures of the human Slo1 K+ channel in complex with β4.
2019,
Pubmed
Tao,
Cryo-EM structure of the open high-conductance Ca2+-activated K+ channel.
2017,
Pubmed
Wang,
Mechanism of increased BK channel activation from a channel mutation that causes epilepsy.
2009,
Pubmed
Wu,
Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel.
2010,
Pubmed
Xia,
Multiple regulatory sites in large-conductance calcium-activated potassium channels.
2002,
Pubmed
Yang,
Mg2+ mediates interaction between the voltage sensor and cytosolic domain to activate BK channels.
2007,
Pubmed
Yang,
BK channels: multiple sensors, one activation gate.
2015,
Pubmed
Yang,
Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains.
2008,
Pubmed
Yang,
An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing.
2010,
Pubmed
,
Xenbase
Yang,
Interaction between residues in the Mg2+-binding site regulates BK channel activation.
2013,
Pubmed
,
Xenbase
Yuan,
Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel.
2011,
Pubmed
Yuan,
Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution.
2010,
Pubmed
Zeng,
Divalent cation sensitivity of BK channel activation supports the existence of three distinct binding sites.
2005,
Pubmed
,
Xenbase
Zhang,
Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels.
2017,
Pubmed
,
Xenbase
Zhang,
Allosteric regulation of BK channel gating by Ca(2+) and Mg(2+) through a nonselective, low affinity divalent cation site.
2001,
Pubmed
,
Xenbase
Zhou,
Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel.
2017,
Pubmed