Cyclopiazonic acid-induced changes in the contraction and Ca 2+ transient of frog fast-twitch skeletal muscle

Abstract : The effects of cyclopiazonic acid (CPA) were investigated on isolated skeletal muscle fibers of frog semitendinosus muscle. CPA (0.5-10 microM) enhanced isometric twitch but produced little change in resting tension. At higher concentrations (10-50 microM), CPA depressed twitch and induced sustained contracture without affecting resting and action potentials. In Triton-skinned fibers, CPA had no significant effect on myofibrillar Ca2+ sensitivity but decreased maximal activated force at concentrations > 5 microM. In intact cells loaded with the Ca2+ fluorescence indicator indo 1, CPA (2 microM) induced an increase in Ca(2+)-transient amplitude (10 +/- 2.5%), which was associated with an increase in time to peak and in the time constant of decay. Consequently, peak force was increased by 35 +/- 4%, and both time to peak and the time constant of relaxation were prolonged. It is concluded that CPA effects, at a concentration of up to 2 microM, were associated with specific inhibition of sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase in intact skeletal muscle and that inhibition of the pump directly affected the handling of intracellular Ca2+ and force production.
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William Même, Corinne Huchet-Cadiou, Claude Léoty. Cyclopiazonic acid-induced changes in the contraction and Ca 2+ transient of frog fast-twitch skeletal muscle. American Journal of Physiology - Cell Physiology, American Physiological Society, 1998, 274 (1), pp.C253-C261. ⟨10.1152/ajpcell.1998.274.1.C253⟩. ⟨hal-02147844⟩

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