Determinants of oxidative phosphorylation onset kinetics in isolated myocytes

At the onset of constant-load exercise, pulmonary oxygen uptake (VO2) exhibits a monoexponential increase, following a brief time delay, to a new steady state. To date, the specific factors controlling VO2 onset kinetics during the transition to higher rates of work remain largely unknown. To study the control of respiration in the absence of confounding factors such as blood flow heterogeneity and fiber type recruitment patterns, the onset kinetics of mitochondrial respiration were studied at the start of contractions in isolated single myocytes. Individual myocytes were microinjected with a porphyrin compound to allow phosphorescent measurement of intracellular PO2 (PiO2, an analog of VO2). Peak tension and PiO2 were continuously monitored under a variety of conditions designed to test the role of work intensity, extracellular PO2, cellular metabolites, and enzyme activation on the regulation of VO2 onset kinetics.