New Insights into the Topography, Gating and Modulation of MaxiK Channels

Abstract

Large conductance voltage and calcium sensitive K channels (MaxiK, Kca, or BK channels) are stimulated upon membrane depolarization and/or by a raise in intracellular calcium. Mammalian MaxiK channels are distinguished from other calcium-sensitive potassium channels, by their large conductance and sensitivities to toxins. For example, they are insensitive to apamin (which inhibits small conductance calcium-activated K channels) and sensitive to charybdotoxin and iberiotoxin (for review see Garcia et al., 1991). MaxiK channels are present in almost every tissue with an important exception, the heart myocytes. Their abundance in the plasma membrane varies from tissue to tissue; the most notable cell type for their high expression are smooth muscles. MaxiK channels are modulators of neuronal excitability in brain (Crest and Gola, 1993; Robitaille et al., 1993) and in smooth muscles they set the level of contractile activity (Anwer et al., 1993; Nelson et al., 1995). One of the mechanisms (perhaps the most important) by which MaxiK channels exert their function is by sensing the intracellular Ca2+ levels in their vicinity (for a comment see Fay, 1995). An increase in intracellular Ca2+, via Ca2+ entry or Ca2+ release from intracellular stores, promotes their activation leading to a prompt hyperpolarization and decrease in neuronal excitability or to relaxation in smooth muscles. Conversely, their inhibition and consequent membrane depolarization causes constriction of smooth muscles (Anwer et al., 1993; Nelson et al., 1995).