Two mechanisms of quantized calcium release in skeletal muscle

SKELETAL muscle uses voltage sensors in the transverse tubular membrane(1-3) that are linked by protein-protein interactions(4-6) to intracellular ryanodine receptors(7-10), which gate the release of calcium from the sarcoplasmic reticulum. Here we show, by using voltage-clamped single fibres and confocal imaging, that sto chastic calcium-release events, visualized as Ca2+ sparks, occur in skeletal muscle and originate at the tried. 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.