Contractile response to low peroxide concentrations: myofibrillar calcium sensitivity as a likely target for redox‐modulation of skeletal muscle function

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Abstract
Endogenous peroxides and related reactive oxygen species may influence various steps in the contractile process. Single mouse skeletal muscle fibers were used to study the effects of hydrogen peroxide (H2O2) andt‐butyl hydroperoxide (f‐BOOH) on force and myoplasmic Ca2+concentration ([Ca2+]i). Both peroxides (10−1to 10−5M) decreased tetanic [Ca2+]iand increased force during submaximal tetani. Catalase (1 kU/ml) blocked the effect of H2O2, but not oft‐BOOH. The decrease in tetanic [Ca2+]iwas constant, while the effect on force was biphasic: A transitory increase was followed by a steady decline to the initial level. Myofibrillar Ca2+sensitivity remained increased during incubation with either peroxide. Only the highest peroxide concentration (10 μM) increased resting [Ca2+]iand slowed the return of [Ca2+]ito its resting level after a contraction, evidence of impaired sarcoplasmic reticulum Ca2+re‐uptake. The peroxides increased maximal force production and the rate of force redevelopment, and decreased maximum shortening velocity. N‐ethylmaleimide (25 μM, thiol‐alkylating agent) prevented the response to 1 μM H2O2. These results show that myofibrillar Ca2+sensitivity and cross‐bridge kinetics are influenced by H2O2 andt‐BOOH concentrations that approach those found physiologically, and these findings indicate a role for endogenous oxidants in the regulation of skeletal muscle function.