Effects of intracellular acidosis on Ca2+ activation, contraction, and relaxation of frog skeletal muscle

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Abstract
The goal of this study was to determine the effects of intracellular acidosis (pH approximately 6.3) of frog skeletal muscle on force and on intracellular Ca2+ concentration ([Ca2+]i; measured at 20 degrees C using indo 1 fluorescence). Acidosis reduced tetanic force by only 11 +/- 2% (mean +/- SE, n = 8) but increased tetanic [Ca2+]i by 33 +/- 6%, suggesting that acidosis reduced the maximum Ca(2+)-activated force. During relaxation, the [Ca2+]i at half-maximal force was doubled with acidosis, suggesting that acidosis altered the Ca(2+)-force relationship. Acidosis markedly slowed force relaxation and [Ca2+]i decline (time constants fitted to force and [Ca2+]i during relaxation increased by 133 +/- 20 and 68 +/- 13%, respectively, with acidosis), suggesting that slowed force relaxation with acidosis may arise from slowed Ca2+ clearance from the cytosol. Late in relaxation, at approximately 30% of initial force, there was a transient phase of [Ca2+]i increase that was delayed with acidosis in proportion to the slowing of force relaxation. This is consistent with previous suggestions that dissociation of cross-bridges from the thin filament during relaxation promotes Ca2+ release to the cytosol from troponin. This study concludes that in skeletal muscle acidosis has little effect on tetanic force and that the major effects are decreased Ca2+ sensitivity and slower relaxation.