Two mechanisms of quantized calcium release in skeletal muscle

SKELETAL muscle uses voltage sensors in the transverse tubular membrane that are linked by protein-protein interactions to intracellular ryanodine receptors, which gate the release of calcium from the sarcoplasmic reticulum. Here we show, by using voltage-clamped single fibres and confocal imaging, that stochastic calcium-release events, visualized as Ca²⁺ sparks, occur in skeletal muscle and originate at the triad. Unitary triadic Ca²⁺ release events are initiated by the voltage sensor in a steeply voltage-dependent manner, or occur spontaneously by a mechanism independent of the voltage sensor. Large amplitude events also occur during depolarization and consist of two or more unitary events. We propose a 'dual control' model for discrete Ca²⁺ release events from the sacroplasmic reticulum that unifies diverse observations about Ca²⁺-signalling in frog skeletal muscle, and that may be applicable to other excitable cells.