EFFECT OF ACIDOSIS ON CONTROL OF RESPIRATION IN SKELETAL-MUSCLE

The relationships between oxygen consumption (QO(2)) and calculated cy toplasmic ADP concentration ( [ADP]) and the free energy of ATP hydrol ysis (Delta G(ATP)) were examined in ex vivo arterially perfused cat s oleus muscles during repetitive twitch stimulation under normocapnic ( 5% CO2) and hypercapnic (70% CO2) conditions. Hypercapnia decreased ex tra- and intracellular pH by over 0.5 but had no significant effect on QO(2) or phosphocreatine (PCr)/ATP in muscles at rest. The maximum QO (2) measured during stimulation and the rate constant for PCr recovery after stimulation both decreased during hypercapnic compared with nor mocapnic perfusion, but the estimated ATP/O-2 was unchanged. The chang e in PCr and Delta G(ATP) with increasing QO(2) was greater during hyp ercapnic compared with normocapnic stimulation, as expected from the d ecrease in maximum QO(2). However, the relationships between QO(2) and [ADP] and Delta G(ATP) were both shifted to the left during hypercapn ia compared with normocapnia. The results show that changes in cytopla smic adenine nucleotides and phosphate are not sufficient to explain t he control of respiration in skeletal muscle. However; in the context of thermodynamic models of respiratory control, the results can be exp lained by increased intramitochondrial potential for ATP synthesis at low pH.