K+ Channel Subfamily M Alpha Subunit 1

From Anvita Health Wiki

Contents 1 Function 2 Structure 3 Compartment 4 Alternative-splicing 5 Expression 6 Pathology 7 Notes 8 More General Terms 9 Internet Database 10 References

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

• contraction of smooth muscle
• tuning of hair cells in the cochlea
• transmitter release
• 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

• alternative splicing
• phosphorylation status
• 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 &/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

• imbedded into the membrane
• forms the selectivity filter of the pore
• 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

• constitutes one of the Ca+2 sensors
• probably acts as a Ca+2-binding site
• other Ca+2 sensors regions are required for activation of the channel

• the heme-binding motif

• mediates inhibition of channel activation by heme
• 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:

• core channel (from the N-terminus to the S9 segment) that mediates the channel activity
• 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

More General Terms

• transmembrane 7 protein
• K+ channel subfamily M
• glycoprotein
• phosphoprotein

Internet Database

Entrez gene: 3778
Kegg: [1]
OMIM: 600150
OMIM: 609446
Prosite: [2]
UniProt: [3]

References

UniProt [4]

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)