Sarcoplasmic reticulum Ca2+ release and muscle fatigue

Efforts to examine the relevant mechanisms involved in skeletal muscle fati gue are focusing on Ca2+ handling within the active muscle cell. It has bee n demonstrated time and again that reductions in sarcoplasmic reticulum (SR ) Ca2+ release resulting from increased or intense muscle contraction will compromise tension development. This review seeks to accomplish two related goals: 1) to provide all up-to-date molecular understanding of the Ca2+-re lease process, with considerable attention devoted to the SR Ca2+ channel, including its associated proteins and their regulation by endogenous compou nds; and 2) to examine several:putative mechanisms by which cellular altera tions resulting from intense and/or prolonged contractile activity will mod ify SR Ca2+ release. The mechanisms that are likely candidates to explain t he reductions in SR Ca2+ channel function following contractile activity in clude elevated Ca2+ concentrations, alterations in metabolic homeostasis wi thin the "microcompartmentalized" triadic space, and modification by reacti ve oxygen species.