Effects of depolarization and low intracellular pH on charge movement currents of frog skeletal muscle fibers

The low intracellular pH and membrane depolarization associated with repeated skeletal muscle stimulation could impair the function of the transverse tubular (t tubule) voltage sensor and result in a decreased sarcoplasmic reticulum Ca2+ release and muscle fatigue. We therefore examined the effects of membrane depolarization and low intracellular pH on the t-tubular charge movement. Fibers were voltage clamped in a double Vaseline gap, at holding potential (HP) of -90 or -60 mV, and studied at an internal pH of 7.0 and 6.2. Decreasing intracellular pH did not significantly alter the maximum amount of charge moved, transition voltage, or steepness factor at either HP. Depolarizing HP significantly decreased steepness factor and maximum charge moved and shifted the transition voltage to more positive potentials. Elevated extracellular Ca2+ decreased the depolarization-induced reduction in the charge movement. These results indicate that, although the decrease in intracellular pH seen in fatigued muscle does not impair the t-tubular charge movement, the membrane depolarization associated with muscle fatigue may be sufficient to inactivate a significant fraction of the t-tubular charge. However, if t-tubular Ca2+ increases, some of the charge may be stabilized in the active state and remain available to initiate sarcoplasmic reticulum Ca2+ release.