Calcium-activated potassium channel subunit alpha-1 also known as large conductance calcium-activated potassium channel, subfamily M, alpha member 1 (KCa1.1), or BK channel alpha subunit, is a voltage gated potassium channel encoded by the KCNMA1gene and characterized by their large conductance of potassium ions (K+) through cell membranes.
BK channels are essential for the regulation of several key physiological processes including smooth muscletone and neuronal excitability. They control the contraction of smooth muscle and are involved with the electrical tuning of hair cells in the cochlea. BK channels also contribute to the behavioral effects of ethanol in the worm C. elegans under high concentrations (> 100 mM, or approximately 0.50% BAC). It remains to be determined if BK channels contribute to intoxication in humans.
BK 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 tetrameric channel. Alternatively spliced transcript variants encoding different isoforms have been identified.
Each BK channel alpha subunit consists of (from N- to C-terminal):
A unique transmembrane domain (S0) that precedes the 6 transmembrane domains (S1-S6) conserved in all voltage-dependent K+ channels.
A voltage sensing domain (S1-S4).
A K+ channel pore domain (S5, selectivity filter, and S6).
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.
Calcium-activated BK potassium channel alpha subunit
BK channels are pharmacological targets for the treatment of stroke. Various pharmaceutical companies developed synthetic molecules activating these channels in order to prevent excessive neurotoxic calcium entry in neurons. But BMS-204352 (MaxiPost) a molecule developed by Bristol-Myers Squibb failed to improve clinical outcome in stroke patients compared to placebo. BK channels have also been found to be activated by exogenous pollutants and endogenous gazotransmitters carbon monoxide and hydrogen sulphide.
Researchers have identified a rare disease in humans caused by mutations in the gene. KCNMA1-linked channelopathy can cause neurological conditions like seizures and movement disorders. An episode of the TV show based on the Diagnosis column in the New York Times was about a young girl with a KCNMA1 disorder that caused transient episodes of muscle weakness.
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