Effects of reactive oxygen species on aspects of excitation-contraction coupling in chemically skinned rabbit diaphragm muscle fibres

Oxidants have been suggested to enhance contractile function in unfatigued muscle. In this study we aimed to determine the effect of oxidants on 'chem ically skinned' diaphragm muscle fibre bundles. The sarcoplasmic reticulum and contractile proteins were exposed to superoxide anions (O-2(-)) and hyd rogen peroxide (H2O2) under controlled conditions. Application of O-2(-) in itially increased maximum Ca2+-activated force but subsequently reduced max imum Ca2+-activated force without altering myofilament Ca2+ sensitivity. Un like myocardium, caffeine-induced Ca2+ release from the sarcoplasmic reticu lum was also inhibited by O-2(-) exposure in diaphragm fibre bundles. Appli cation of H2O2 also increased maximum Ca2+-activated force but had addition al effects on resting tension (which increased to 25 % of the control maxim um Ca(2+)activated force). H2O2 was without effect on myofilament Ca2+ sens itivitS or caffeine-induced Ca2+ release from the sarcoplasmic reticulum, T hese data demonstrate that oxidants can potentiate contractile force in the diaphragm through a direct action on the contractile proteins. The potenti ation of force is not sustained, however, and under these conditions the de trimental effects of O-2(-) on Ca2+ release from the sarcoplasmic reticulum combined with the effects of oxidants on the contractile proteins mill ult imately compromise excitation-contraction coupling in the diaphragm.