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Department of Biology, Marquette University, Milwaukee, Wisconsin 53210
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.
muscle fatigue; excitation-contraction coupling; sarcoplasmic reticulum; transverse tubule
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