Calcium exchange hypothesis of skeletal muscle fatigue: a brief review.

Abstract

Skeletal muscle fatigue is often associated with diminished athletic performance and work productivity as well as increased susceptibility to injury. The exact cause of muscle fatigue probably involves a number of factors which influence force production in a manner dependent on muscle fiber type and activation pattern. However, a growing body of evidence implicates alterations in intracellular Ca2+ exchange as a major role in the fatigue process. These changes are thought to occur secondary to reductions in the rates of Ca2+ uptake and release by the sarcoplasmic reticulum (SR). This hypothesis is based on the finding that peak myoplasmic Ca2+ concentration ([Ca2+]i) is reduced as force declines during fatigue. In addition, direct measurements of Ca2+ uptake and release show that fatiguing activity causes intrinsic alterations in the functional properties of the SR. We also propose that fatigue-induced alterations in Ca2+ exchange may be beneficial, reducing the rate of energy utilization by the muscle fiber and preventing irreversible damage to the cell.