BK channels in Ca²⁺ store control Ca²⁺ release

Abstract

Ca²⁺ release from intracellular Ca²⁺ stores terminates after a rapid release of a fraction of releasable Ca²⁺ (called "quantal" release). To explain the quantal nature, it has been hypothesized that a decrease in luminal Ca²⁺ attenuates Ca²⁺ efflux. However, the mechanism remains an enigma. We show that voltage- and Ca²⁺-activated potassium channels in Ca²⁺ store control Ca²⁺ release. The potassium channel was identified as BK-type by patch-clamp recordings from an enlarged nuclear envelope in the nucleus-attached mode and by immunolabeling. The store BK channel was activated by positive shifts in luminal potential and luminal Ca²⁺ increases. The closing or blockage of store BK channels developed lumen-negative potentials and suppressed Ca²⁺ release. Ca²⁺ uptake by store Ca²⁺ pumps would reactivate the store BK channels regeneratively with K⁺ entry to allow repetitive Ca²⁺ release. Indeed, the luminal potential oscillated bistably ∼45 mV in amplitude as revealed with an organelle-specific voltage-sensitive dye [DiOC₅(3)]. Our study suggests that Ca²⁺ release-induced closings of store BK channels cause a lumen-negative potential towards the equilibrium potential for Ca²⁺ to attenuate Ca²⁺ efflux. [J Physiol Sci. 2006;56 Suppl:S151]