title: Impaired calcium release during fatigue.
abstract: Impaired calcium release from the sarcoplasmic reticulum (SR) has been identified as a contributor to fatigue in isolated skeletal muscle fibers. The functional importance of this phenomenon can be quantified by the use of agents, such as caffeine, which can increase SR Ca(2+) release during fatigue. A number of possible mechanisms for impaired calcium release have been proposed. These include reduction in the amplitude of the action potential, potentially caused by extracellular K(+) accumulation, which may reduce voltage sensor activation but is counteracted by a number of mechanisms in intact animals. Reduced effectiveness of SR Ca(2+) channel opening is caused by the fall in intracellular ATP and the rise in Mg(2+) concentrations that occur during fatigue. Reduced Ca(2+) available for release within the SR can occur if inorganic phosphate enters the SR and precipitates with Ca(2+). Further progress requires the development of methods that can identify impaired SR Ca(2+) release in intact, blood-perfused muscles and that can distinguish between the various mechanisms proposed.
authors.affiliation: School of Medical Sciences and Bosch Institute, Univ. of Sydney F13, NSW 2006, Australia. davida@physiol.usyd.edu.au
authors.forename: D G
authors.initials: DG
authors.lastname: Allen
authors.forename: G D
authors.initials: GD
authors.lastname: Lamb
authors.forename: H
authors.initials: H
authors.lastname: Westerblad
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D015444:Exercise / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating; D009119:Muscle Contraction; D018763:Muscle Fatigue; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009126:Muscle Relaxation; D018482:Muscle, Skeletal / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium