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 μM; Ca²⁺ release from the sarcoplasmic reticulum was monitored as an isometric tension transient. The response to 0.5 μM 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 sacroplasmic 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.