Structure of sarcoplasmic reticulum and activity-induced alteration in its function

Abstract

Repeated contractions of skeletal muscle lead to a decline of force known as fatigue. The exact cause of muscular fatigue probably involves numerous factors which influence force production in a manner dependent on muscle fiber type and activation pattern. However, a growing amount of evidence implicates alteration of intracellular Ca^2+ handling as a major contributor to fatigue. These changes are known to occur secondary to reductions in the rates of Ca^2+ uptake and release by the sarcoplasmic reticulum (SR). In this brief review, we focus on two major aspects: 1) molecular mechanisms of the Ca^2+ uptake and release process, focusing on Ca^2+-ATPase protein and the ryanodine receptor; and 2) several factors that may be responsible for dysfunction of the SR resulting from contractile activity. Factors that might account for diminished function of the SR include a fall in internal pH, increased Ca^2+ concentration, modification by reactive oxygen species, depletion of high-energy phosphate, and accumulation of inorganic phosphate.