Voltage dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in peeled skeletal muscle fibers.

Excitation-contraction coupling in skeletal muscle is known to be under absolute control of plasmalemma voltage, but the steps from transverse (T)-tubule depolarization to Ca2+ release from the sarcoplasmic reticulum have not been elucidated. The effect of changing T-tubule membrane potential on inositol 1,4,5-trisphosphate (InsP3) stimulation of Ca2+ release from the sarcoplasmic reticulum was studied to explore a possible role for InsP3 as a chemical signal in excitation-contraction coupling. InsP3 was microinjected into peeled rabbit skeletal muscle fibers at a pipette concentration of 0.5 microM; Ca2+ release from the sarcoplasmic reticulum was monitored as an isometric tension transient. The response to 0.5 microM InsP3 was significantly larger when T-tubules were in a depolarized state than when they were in a polarized state, and this difference in response was independent of the ionic composition of the bathing solutions or the method for depolarizing the T-tubules. Thus, T-tubule depolarization may sensitize the sarcoplasmic reticulum to a preexisting low concentration of InsP3 and greatly reduce the need for InsP3 production. Plasmalemma voltage control of the stimulatory effects of InsP3 may have relevance for mechanisms in excitable nonmuscle cells.