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Two mechanisms of quantized calcium release in skeletal muscle

Abstract

SKELETAL muscle uses voltage sensors in the transverse tubular membrane1–3 that are linked by protein–protein interactions4–6 to intracellular ryanodine receptors7–10, 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.

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Klein, M., Cheng, H., Santana, L. et al. Two mechanisms of quantized calcium release in skeletal muscle. Nature 379, 455–458 (1996). https://doi.org/10.1038/379455a0

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