Voltage‐ and Ca2+‐activated potassium channels in Ca2+ store control Ca2+ release

Ca2+ release from Ca2+ stores is a ‘quantal’ process; it terminates after a rapid release of stored Ca2+. To explain the quantal nature, it has been supposed that a decrease in luminal Ca2+ acts as a ‘brake’ on store release. However, the mechanism for the attenuation of Ca2+ efflux remains unknown. We show that Ca2+ release is controlled by voltage‐ and Ca2+‐activated potassium channels in the Ca2+ store. The potassium channel was identified as the big or maxi‐K (BK)‐type, and was activated by positive shifts in luminal potential and luminal Ca2+ increases, as revealed by patch‐clamp recordings from an exposed nuclear envelope. The blockage or closure of the store BK channel due to Ca2+ efflux developed lumen‐negative potentials, as revealed with an organelle‐specific voltage‐sensitive dye [DiOC5(3); 3,3’‐dipentyloxacarbocyanine iodide], and suppressed Ca2+ release. The store BK channels are reactivated by Ca2+ uptake by Ca2+ pumps regeneratively with K+ entry to allow repetitive Ca2+ release. Indeed, the luminal potential oscillated bistably by ∼45 mV in amplitude. Our study suggests that Ca2+ efflux‐induced store BK channel closures attenuate Ca2+ release with decreases in counter‐influx of K+.