Hydrogen peroxide disrupts Ca2+ release from the sarcoplasmic reticulum of rat skeletal muscle fibers.
Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low levels in resting muscles and at substantially higher levels in exercising muscles. Increased respiratory activity with exercise leads to O2- production by the NADPH oxidase reaction and the subsequent generation of H2O2 from O2- by spontaneous dismutation or by the superoxide dismutase reaction. The long-lasting (24-h) depression of contractile function after exercise has been linked to damage of one or more proteins important in the excitation-contraction coupling process. We studied mechanically and chemically skinned fibers from the extensor digitorum longus muscle of the rat to evaluate the effects of a 5-min exposure to 1.0 mM H2O2 on muscle function. We found that H2O2 had no effect on the isometric force-producing properties of the contractile apparatus or on Ca2+ uptake by the sarcoplasmic reticulum. It did, however, significantly affect Ca2+ release from the sarcoplasmic reticulum. Maximum depolarization-induced Ca2+ release was inhibited, and the sensitivity to depolarization was decreased. Ca(2+)-induced release was completely blocked. We conclude that elevated levels of H2O2 with exercise are capable of damaging one or more proteins of the excitation-contraction coupling process to produce a disruption in function that can account, at least in part, for the long-lasting effects of fatiguing stimulation.
Brotto
M A
MA
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000, USA.
Nosek
T M
TM
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D009124:Muscle Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002118:Calcium