Potassium large conductance calcium-activated channel, subfamily M, alpha 1

Potassium large conductance calcium-activated channel, subfamily M, alpha member 1
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Available structures PDB 2K44, 3MT5, 3NAF
Identifiers
Symbols	KCNMA1; BKTM; DKFZp686K1437; KCa1.1; MGC71881; MaxiK; SAKCA; SLO; SLO-ALPHA; SLO1; bA205K10.1; mSLO1
External IDs	OMIM: 600150 MGI: 99923 HomoloGene: 1693 IUPHAR: KCa1.1 GeneCards: KCNMA1 Gene
Gene Ontology Molecular function • actin binding • voltage-gated ion channel activity • voltage-gated potassium channel activity • protein binding • calcium-activated potassium channel activity • metal ion binding • large conductance calcium-activated potassium channel activity • large conductance calcium-activated potassium channel activity Cellular component • caveola • voltage-gated potassium channel complex • membrane • integral to membrane • apical plasma membrane Biological process • response to hypoxia • ion transport • potassium ion transport • response to osmotic stress • blood coagulation • cellular potassium ion homeostasis • platelet activation • response to carbon monoxide • response to carbon monoxide • regulation of membrane potential • positive regulation of apoptosis • negative regulation of cell volume • response to calcium ion • transmembrane transport • micturition • smooth muscle contraction involved in micturition • potassium ion transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3778	16531
Ensembl	ENSG00000156113	ENSMUSG00000063142
UniProt	Q12791	Q3TSL8
RefSeq (mRNA)	NM_001014797.2	NM_010610.2
RefSeq (protein)	NP_001014797.1	NP_034740.2
Location (UCSC)	Chr 10: 78.64 – 79.4 Mb	Chr 14: 24.12 – 24.62 Mb
PubMed search	[1]	[2]

Calcium-activated potassium channel subunit alpha-1 also known as potassium large conductance calcium-activated channel, subfamily M, alpha member 1 (K_Ca1.1) is a voltage gated ion channel encoded by the KCNMA1 gene.

Function

K_Ca1.1 channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability.

Structure

K_Ca1.1 channels have a tetrameric structure. Each monomer of the channel-forming alpha subunit is the product of the KCNMA1 gene. Modulatory beta subunits (encoded by KCNMB1, KCNMB2, KCNMB3, or KCNMB4) can associate with the tetrametic channel. Alternatively spliced transcript variants encoding different isoforms have been identified.

Each K_Ca1.1 channel alpha subunit consists of (from N- to C-terminal):

1. A unique transmembrane domain (S0) that precedes the 6 transmembrane domains (S1-S6) conserved in all voltage-dependent K⁺ channels.
2. A voltage sensing domain (S1-S4).
3. A K⁺ channel pore domain (S5, selectivity filter, and S6).
4. A cytoplasmic C-terminal domain (CTD) consisting of a pair of RCK domains that assemble into an octameric gating ring on the intracellular side of the tetrameric channel. The CTD contains four primary binding sites for Ca²⁺, called "calcium bowls", encoded within the second RCK domain of each monomer.

Available X-ray structures:

• 3MT5 - Crystal Structure of the Human BK Gating Apparatus
• 3NAF - Structure of the Intracellular Gating Ring from the Human High-conductance Ca2+ gated K+ Channel (BK Channel)

See also

• BK channel
• Voltage-gated potassium channel

Further reading

• Magleby KL (2003). "Gating mechanism of BK (Slo1) channels: so near, yet so far.". J. Gen. Physiol. 121 (2): 81–96. doi:10.1085/jgp.20028721. PMC 2217328. PMID 12566537. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2217328. 
• Wei AD, Gutman GA, Aldrich R, et al. (2006). "International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels.". Pharmacol. Rev. 57 (4): 463–72. doi:10.1124/pr.57.4.9. PMID 16382103. 
• McCobb DP, Fowler NL, Featherstone T, et al. (1995). "A human calcium-activated potassium channel gene expressed in vascular smooth muscle.". Am. J. Physiol. 269 (3 Pt 2): H767–77. PMID 7573516. 
• Butler A, Tsunoda S, McCobb DP, et al. (1993). "mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.". Science 261 (5118): 221–4. Bibcode 1993Sci...261..221B. doi:10.1126/science.7687074. PMID 7687074. 
• Dworetzky SI, Trojnacki JT, Gribkoff VK (1995). "Cloning and expression of a human large-conductance calcium-activated potassium channel.". Brain Res. Mol. Brain Res. 27 (1): 189–93. doi:10.1016/0169-328X(94)90203-8. PMID 7877450. 
• Pallanck L, Ganetzky B (1995). "Cloning and characterization of human and mouse homologs of the Drosophila calcium-activated potassium channel gene, slowpoke.". Hum. Mol. Genet. 3 (8): 1239–43. doi:10.1093/hmg/3.8.1239. PMID 7987297. 
• Tseng-Crank J, Foster CD, Krause JD, et al. (1995). "Cloning, expression, and distribution of functionally distinct Ca(2+)-activated K+ channel isoforms from human brain.". Neuron 13 (6): 1315–30. doi:10.1016/0896-6273(94)90418-9. PMID 7993625. 
• Knaus HG, Folander K, Garcia-Calvo M, et al. (1994). "Primary sequence and immunological characterization of beta-subunit of high conductance Ca(2+)-activated K+ channel from smooth muscle.". J. Biol. Chem. 269 (25): 17274–8. PMID 8006036. 
• Meera P, Wallner M, Jiang Z, Toro L (1996). "A calcium switch for the functional coupling between alpha (hslo) and beta subunits (KV,Ca beta) of maxi K channels.". FEBS Lett. 382 (1-2): 84–8. doi:10.1016/0014-5793(96)00151-2. PMID 8612769. 
• Wallner M, Meera P, Ottolia M, et al. (1996). "Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium.". Recept. Channels 3 (3): 185–99. PMID 8821792. 
• Wallner M, Meera P, Toro L (1997). "Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus.". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14922–7. Bibcode 1996PNAS...9314922W. doi:10.1073/pnas.93.25.14922. PMC 26238. PMID 8962157. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26238. 
• Meera P, Wallner M, Song M, Toro L (1998). "Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus.". Proc. Natl. Acad. Sci. U.S.A. 94 (25): 14066–71. Bibcode 1997PNAS...9414066M. doi:10.1073/pnas.94.25.14066. PMC 28433. PMID 9391153. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=28433. 
• Díaz L, Meera P, Amigo J, et al. (1999). "Role of the S4 segment in a voltage-dependent calcium-sensitive potassium (hSlo) channel.". J. Biol. Chem. 273 (49): 32430–6. doi:10.1074/jbc.273.49.32430. PMID 9829973. 
• Wallner M, Meera P, Toro L (1999). "Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog.". Proc. Natl. Acad. Sci. U.S.A. 96 (7): 4137–42. Bibcode 1999PNAS...96.4137W. doi:10.1073/pnas.96.7.4137. PMC 22433. PMID 10097176. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22433. 
• Valverde MA, Rojas P, Amigo J, et al. (1999). "Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit.". Science 285 (5435): 1929–31. doi:10.1126/science.285.5435.1929. PMID 10489376. 
• Brenner R, Jegla TJ, Wickenden A, et al. (2000). "Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.". J. Biol. Chem. 275 (9): 6453–61. doi:10.1074/jbc.275.9.6453. PMID 10692449. 
• Liu QH, Williams DA, McManus C, et al. (2000). "HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation.". Proc. Natl. Acad. Sci. U.S.A. 97 (9): 4832–7. Bibcode 2000PNAS...97.4832L. doi:10.1073/pnas.090521697. PMC 18318. PMID 10758170. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18318. 
• Quirk JC, Reinhart PH (2001). "Identification of a novel tetramerization domain in large conductance K(ca) channels.". Neuron 32 (1): 13–23. doi:10.1016/S0896-6273(01)00444-5. PMID 11604135. 
• Soto MA, González C, Lissi E, et al. (2002). "Ca(2+)-activated K+ channel inhibition by reactive oxygen species.". Am. J. Physiol., Cell Physiol. 282 (3): C461–71. doi:10.1152/ajpcell.00167.2001. PMID 11832330. 
• Wang YW, Ding JP, Xia XM, Lingle CJ (2002). "Consequences of the stoichiometry of Slo1 alpha and auxiliary beta subunits on functional properties of large-conductance Ca2+-activated K+ channels.". J. Neurosci. 22 (5): 1550–61. PMID 11880485. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.