Ca+2-activated K+ channel subunit alpha-1; BK channel; BKCA alpha; Ca+2-activated K+ channel, subfamily M subunit alpha-1; K(VCA)alpha; KCa1.1; Maxi K channel; MaxiK; Slo-alpha; Slo1; Slowpoke homolog; Slo homolog; hSlo (KCNMA1, KCNMA, SLO)

Function: - K⁺ channel activated by both membrane depolarization or increase in cytosolic Ca⁺² that mediates export of K⁺ - also activated by the concentration of cytosolic Mg⁺² - activation dampens the excitatory events that elevate cytosolic Ca⁺² concentration &/or depolarize the cell membrane, thus contributes to repolarization of the membrane potential - role in regulating excitability, involving a) contraction of smooth muscle b) tuning of hair cells in the cochlea c) transmitter release d) innate immunity - in smooth muscles, its activation by high level of Ca⁺², caused by ryanodine receptors in the sarcoplasmic reticulum, regulates membrane potential - in cochlea cells, its number & kinetic properties partly determine the characteristic frequency of each hair cell & thus helps to establish a tonotopic map - kinetics of KCNMA1 channels are determined by a) alternative splicing b) phosphorylation status c) combination with modulating beta subunits - highly sensitive to both iberiotoxin (IbTx) & charybdotoxin (CTX) - ethanol & carbon monoxide-bound heme increase channel activation - heme inhibits channel activation - phosphorylated (probable) by kinases such as PKA &/or PKG - in smooth muscles, phosphorylation affects activity - homotetramer; which constitutes the Ca⁺²-activated K⁺ channel - interacts with beta subunits KCNMB1, KCNMB2, KCNMB3 & KCNMB4 - beta subunits are accessory, & modulate its activity Structure: - the S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 & KCNMB4 - the S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor - the pore-forming domain (also referred as P region) is a) imbedded into the membrane b) forms the selectivity filter of the pore c) contains the signature sequence of K⁺ channels that displays selectivity to K⁺ - the RCK N-terminal domain mediates the homotetramerization, thus promoting the assembly of monomers into functional K⁺ channel - includes binding sites for Ca⁺² & Mg⁺² (putative) - the Ca⁺² bowl a) constitutes one of the Ca⁺² sensors b) probably acts as a Ca⁺²-binding site c) other Ca⁺² sensors regions are required for activation of the channel - the heme-binding motif a) mediates inhibition of channel activation by heme b) carbon monoxide-bound heme leads to increased channel activation - belongs to the K⁺ channel family, Ca⁺²- - activated (TC 1.A.1.3) subfamily, KCa1.1/KCNMA1 sub-subfamily - contains 1 RCK N-terminal domain Compartment: membrane Alternative splicing: - named isoforms=7 - may be partially controlled by hormonal stress - additional isoforms seem to exist Expression: - widely expressed - not expressed in myocytes Pathology: - defects in KCNMA1 are the cause of generalized epilepsy & paroxysmal dyskinesia Notes: - initially thought to contain 2 functionally distinct parts: a) core channel (from the N-terminus to the S9 segment) that mediates the channel activity b) cytoplasmic tail (from the S9 segment to the C-terminus) that mediates the Ca⁺² sensing - however, some integration of function since the core channel also contains binding sites for Ca⁺² & Mg⁺²

General

glycoprotein K+ channel subfamily M phosphoprotein transmembrane 7 protein

Properties

SIZE: entity length = 1236 aa MW = 138 kD COMPARTMENT: plasma membrane MOTIF: exoplasmic domain {1-86} MOTIF: glycine-rich region {4-10} glycine-rich region {13-20} serine-rich region {39-60} MOTIF: serine residue (SEVERAL) transmembrane domain {87-107} cytoplasmic loop {108-178} transmembrane domain {179-199} exoplasmic loop {200-214} transmembrane domain {215-235} cytoplasmic loop {236-239} transmembrane domain {240-260} exoplasmic loop {261-264} transmembrane domain {265-285} cytoplasmic loop {286-300} transmembrane domain {301-321} exoplasmic loop {322-335} peptide motif {352-355} exoplasmic loop {359-367} transmembrane domain {368-388} cytoplasmic domain {389-1236} MOTIF: domain {415-558} Mg+2-binding site SITE: 439-439 Mg+2-binding site SITE: 462-462 Mg+2-binding site SITE: 464-464 domain {556-576} Ser phosphorylation site {S569} domain {613-633} binding site SITE: 677-681 FOR-BINDING-OF: heme Thr phosphorylation site {T763} Ser phosphorylation site {S765} domain {837-857} Ser phosphorylation site {S977} Ser phosphorylation site {S978} peptide motif {1003-1025} domain {1032-1052} Tyr phosphorylation site {Y1086} Thr phosphorylation site {T1088} ION-PERMEABILITY: K+

Database Correlations

OMIM correlations UniProt Q12791 PFAM correlations Entrez Gene 3778 Kegg hsa:3778

References

UniProt :accession Q16558