Effect of intracellular pH on force development depends on temperature in intact skeletal muscle from mouse

The cellular mechanism of muscle fatigue is still in debate. Opposite conclusions regarding the role of intracellular pH (pH(i)) in fatigue have been drawn from skinned fiber vs. isolated perfused muscle studies. Because these experiments are typically performed at different temperatures, we tested the hypothesis that temperature alters the effects of pH on force. Tetanic force of isolated mouse extensor digitorum longus was measured at temperatures between 13 and 25 degrees C in either normocapnia 15% CO2) or hypercapnia (25% CO2). Hypercapnia decreased pH(i) (monitored by P-31 nuclear magnetic resonance spectroscopy) by the same amount at bath 15 and 25 degrees C. However, inhibition of force by hypercapnia was greater at the lower temperature. A similar pattern of temperature-dependent inhibition of force by pH was observed in glycerinated fibers from rabbit psoas at maximum Ca2+ activation. We conclude that temperature differences are responsible for disparate conclusions on the role of pH(i) in muscle fatigue. Based on our results, we suggest that changes in pH(i) may have little or no role in the loss in force production associated with muscular fatigue at physiological temperatures.