SKELETAL muscle uses voltage sensors in the transverse tubular membran
e(1-3) that are linked by protein-protein interactions(4-6) to intrace
llular ryanodine receptors(7-10), which gate the release of calcium fr
om the sarcoplasmic reticulum. Here we show, by using voltage-clamped
single fibres and confocal imaging, that sto chastic calcium-release e
vents, visualized as Ca2+ sparks, occur in skeletal muscle and origina
te at the tried. Unitary triadic Ca2+-release events are initiated by
the voltage sensor in a steeply voltage-dependent manner, or occur spo
ntaneously by a mechanism independent of the voltage sensor. Large amp
litude events also occur during depolarization and consist of two or m
ore 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 m
ay be applicable to other excitable cells.