Cyclopiazonic acid-induced changes in the contraction and Ca2+ 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 μM) enhanced isometric twitch but produced little change in resting tension. At higher concentrations (10–50 μM), 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 μM. In intact cells loaded with the Ca2+fluorescence indicator indo 1, CPA (2 μM) induced an increase in Ca2+-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 μM, were associated with specific inhibition of sarcoplasmic reticulum Ca2+-adenosinetriphosphatase in intact skeletal muscle and that inhibition of the pump directly affected the handling of intracellular Ca2+ and force production.