RISC (Repolarization-induced stop of caffeine-contracture) is not due to store depletion in cultured murine skeletal muscle.

We have combined the patch-clamp technique with Fura-2 measurements to investigate whether RISC (repolarization-induced stop of caffeine-contracture) is a consequence of store depletion in cultured skeletal muscles of rats and mice. Weak depolarizations (-45 to -40 mV) of long duration induced a barely detectable Ca2+ transient. Even under these conditions, caffeine-activated Ca2+transients (CafTs) were terminated upon membrane repolarization (-70 mV) at all stages of CafT. Following the peak of the CafT, massive Ca2+ release was elicited by either flash-photolysis of caged Ca2+ or further depolarization to 0 mV, demonstrating the lack of store depletion. Thus, RISC is not due primarily to store depletion but to closure of the Ca2+ release channels possibly through a mechanical interaction with voltage sensors. RISC was not present in rat heart muscle, further supporting a role of direct interaction in skeletal muscle.