Coupling and cooperativity in voltage activation of a limited-state BK channel gating in saturating Ca

Large conductance Ca-activated K (BK) channels are activated by membrane depolarization and intracellular Ca and Mg (Latorre and Brauchi, 2006; Lu et al., 2006; Salkoff et al., 2006; Cui et al., 2009; for review see Magleby, 2003). Once activated, the K efflux through the opened channel drives the membrane potential in the negative direction. Through this mechanism, BK channels sense both depolarization and intracellular divalent cations to control membrane excitability through a negative feedback loop. BK channels are tetramers comprised of four pore-forming  subunits (Adelman et al., 1992). The membrane-spanning segments S1–S6 of the  subunits share similarities with the family of voltage-gated K channels (Butler et al., 1993). In addition to S1–S6, the BK channel  subunit has a unique S0 transmembrane segment (Meera et al., 1997) as well