Large-conductance calcium-activated potassium channel (KCNMA1 alpha subunit) (BK channel (BK; BKCa; Maxi-K; KCa1.1; Slo1))

The Large-conductance calcium-activated potassium channel is a tetrameric voltage- and Ca2+-activated K+ channel with exceptionally high single-channel conductance (~250–300 pS) that hyperpolarizes membranes by facilitating K+ efflux when activated by depolarization and/or elevated intracellular Ca2+. Its pore-forming alpha subunit is encoded by KCNMA1 (Slo1/KCa1.1) and contains seven transmembrane segments (S0–S6) with a voltage-sensor domain (S0–S4), a pore-gate domain (S5–S6), and a large cytosolic C-terminus with two RCK domains (RCK1/2) that harbor Ca2+ binding sites. Association with auxiliary β1–β4 and γ1–γ4 subunits diversifies gating kinetics, voltage/Ca2+ sensitivity, and pharmacology, enabling tissue-specific function. BK channels are widely expressed and key to limiting excitability by providing rapid negative feedback to Ca2+ influx, thereby regulating neuronal firing, neurotransmitter release, smooth muscle tone, circadian rhythms, hearing, renal and vascular physiology. Dysregulation or deficiency is linked to hypertension and neurodevelopmental disorders, and pharmacologic modulators include peptide blockers (e.g., iberiotoxin, with β4-dependent resistance) and small-molecule/openers (e.g., NS1619, BMS-191011) as well as steroidal enhancement in αβ complexes (17β-estradiol).

Other names

Big potassium channelMaxiKBKCaKCa1.1Slo1BK alpha subunitPotassium channel subfamily M alpha 1KCNMA1 channel

Blockers (e.g., iberiotoxin) bind the external pore and inhibit K+ efflux, increasing excitability; β4 subunit confers resistance to IbTX Activators/openers (e.g., NS1619, BMS-191011) increase BK open probability to enhance K+ efflux, promoting hyperpolarization and reduced Ca2+ entry Steroid modulation (17β-estradiol) enhances BK activity via αβ complexes, altering vascular and neuronal excitability Auxiliary subunit–dependent gating/inactivation: β2 subunit mediates ball-and-chain inactivation of human BK in the Ca2+-bound open state