CYCLOPIAZONIC ACID-INDUCED CHANGES IN THE CONTRACTION AND CA2-TWITCH SKELETAL-MUSCLE( TRANSIENT OF FROG FAST)

The effects of cyclopiazonic acid (CPA) were investigated on isolated skeletal muscle fibers of frog semitendinosus muscle. CPA (0.5-10 mu M ) enhanced isometric twitch but produced little change in resting tens ion. At higher concentrations (10-50 mu M), CPA depressed twitch and i nduced sustained contracture without affecting resting and action pote ntials. In Triton-skinned fibers, CPA had no significant effect on myo fibrillar Ca2+ sensitivity but decreased maximal activated force at co ncentrations >5 mu M. In intact cells loaded with the Ca2+ fluorescenc e indicator indo 1, CPA (2 mu M) induced an increase in Ca2+-transient amplitude (10 +/- 2.5%), which was associated with an increase in tim e 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 constan t of relaxation were prolonged. It is concluded that CPA effects, at a concentration of up to 2 mu M, were associated with specific inhibiti on of sarcoplasmic reticulum Ca2+-adenosinetriphosphatase in intact sk eletal muscle and that inhibition of the pump directly affected the ha ndling of intracellular Ca2+ and force production.