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 repeat ed skeletal muscle stimulation could impair the function of the transverse tubular (t tubule) voltage sensor and result in a decreased sarcoplasmic re ticulum 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 am ount of charge moved, transition voltage, or steepness factor at either HP. Depolarizing HP significantly decreased steepness factor and maximum charg e moved and shifted the transition voltage to more positive potentials. Ele vated 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 char ge 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 stabilize d in the active state and remain available to initiate sarcoplasmic reticul um Ca2+ release.