Muscle intracellular oxygenation during exercise: optimization for oxygen transport, metabolism, and adaptive change

Abstract

Exercise is the example par excellence of the body functioning as a physiological system. Conventionally we think of the O₂ transport process as a major manifestation of that system linking and integrating pulmonary, cardiovascular, hematological and skeletal muscular contributions to the task of getting O₂ from the air to the mitochondria, and this process has been well described. However, exercise invokes system responses at levels additional to those of macroscopic O₂ transport. One such set of responses appears to center on muscle intracellular PO₂, which falls dramatically from rest to exercise. At rest, it approximates 4 kPa, but during heavy endurance exercise it falls to about 0.4–0.5 kPa, an amazingly low value for a tissue absolutely dependent on the continual supply of O₂ to meet very high energy demands. One wonders why intracellular PO₂ is allowed to fall to such levels. The proposed answer, to be presented in the review, is that a low intramyocyte PO₂ is pivotal in: (a) optimizing oxygen’s own physiological transport, and (b) stimulating adaptive gene expression that, after translation, enables greater exercise capacity—all the while maintaining PO₂ at levels sufficient to allow oxidative phosphorylation to operate sufficiently fast enough to support intense muscle contraction. Thus, during exercise, reductions of intracellular PO₂ to less than 1% of that in the atmosphere enables an integrated response that fundamentally and simultaneously optimizes physiological, biochemical and molecular events that support not only the exercise as it happens but the adaptive changes to increase exercise capacity over the longer term.