Calcium exchange hypothesis of skeletal muscle fatigue: a brief review

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.