Key result
Phosphorylating Ca2+-Mg2+ ATPase without Mg2+ or with quercetine drives rapid Ca2+ release from SR vesicles.
This study proposes a molecular mechanism for phosphoenzyme-mediated Ca2+ release based on rapid shuttling of ATPase molecules between ADP-sensitive and ADP-insensitive phosphorylated states.
May inform SR Ca2+ release models in skeletal muscle; leaves open relevance to cardiac physiology or disease.
A rapid Ca2+ release from Ca2+-loaded sarcoplasmic reticulum vesicles from fast skeletal muscle can be induced under conditions which permit the formation of a stable phosphorylated intermediate of the (Ca2+-Mg2+)-ATPase. Such a state can be achieved experimentally by phosphorylating the ATPase in the absence of Mg2+ ions, which otherwise would stimulate the dephosphorylation step(s). Also, quercetine stimulates the rapid release of Ca2+ if used in the concentration range which does not produce inhibition of phosphoenzyme formation, but which inhibits phosphoenzyme dephosphorylation. The rapid efflux of Ca2+ ions proceeds as long as the low affinity Ca2+-binding sites facing the lumen of the vesicles are saturated and as long as Ca2+ is removed from the catalytic sites facing the cytosol. A molecular mechanism of the phosphoenzyme-mediated Ca2+ release is proposed. This mechanism is based on a rapid shuttling of the ATPase molecules between an ADP-sensitive and an ADP-insensitive phosphorylated state.
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Chiesi et al. (1983) studied Fast skeletal muscle sarcoplasmic reticulum vesicles. Phosphorylation of ATPase in the absence of Mg2+ ions or with quercetine was evaluated on Rapid Ca2+ release. A stable phosphorylated intermediate of the (Ca2+-Mg2+)-ATPase, achieved by phosphorylating the ATPase without Mg2+ or with quercetine, mediates rapid Ca2+ release from sarcoplasmic reticulum vesicles.
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