CHANGES IN POTENTIAL CONTROLLERS OF HUMAN SKELETAL-MUSCLE RESPIRATION DURING INCREMENTAL CALF EXERCISE

The purpose of this study was to evaluate the consequences of nonlinear changes in phosphocreatine (PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energy of ATP hydrolysis (Delta G(ATP)). Six subjects performed incremental plantar flexion exercise on a treadle ergometer while muscle P-i metabolism (PCr, P-i, ATP) and pH were followed using P-31-nuclear magnetic resonance spectroscopy. Changes in ADP and Delta G(ATP) were estimated with the assumption that there was equilibrium of the creatine kinase reaction and homogeneous tissue metabolite pools. All six subjects showed a threshold for onset of cellular acidosis that occurred on average at 47.3 +/- 12.7% of peak work rate (PWR). In five of the six subjects, PCr and P-i showed accelerated rates of change above the threshold for onset of cellular acidosis. In all six subjects, ADP, when correctly calculated considering changes in pH, rose in a curvilinear fashion that was well described by a Michaelis-Menten hyperbola through 60-100% of PWR, with a mean apparent Michaelis-Menten constant of 43.1 +/- 17.1 mu M ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 +/- 94% of PWR. Delta G(ATP) rose linearly with work rate from -62.9 +/- 1.8 kJ/mol during unloaded treadling to -55.0 +/- 1.8 kJ/mol at PWR. If we assume a linear O-2 uptake-to-work rate relationship, these results are most consistent with control of respiration being exerted through Delta G(ATP) under these conditions (incremental exercise by human calf muscle). These data suggest that the changes in PCr (and ultimately changes in ADP as well) with increasing work rate reflect shifts in substrate concentrations that are dictated and/or required under changing acid-base conditions by the linear rise in Delta G(ATP).