Cyclopiazonic acid-induced changes in the contraction and Ca2+ transient of frog fast-twitch skeletal muscle

• Published in: The American journal of physiology Vol. 274; no. 1; pp. C253 - C261
• Main Authors: Même, W, Huchet-Cadiou, C, Léoty, C
• Format: Journal Article
• Language: English
• Published: United States 01-01-1998
• Subjects: Animals; Calcium - metabolism; Calcium-Transporting ATPases - antagonists & inhibitors; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Indoles - pharmacology; Isometric Contraction - drug effects; Muscle Fibers, Fast-Twitch - drug effects; Muscle Fibers, Fast-Twitch - physiology; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; Rana esculenta; Space life sciences; Time Factors
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1998.274.1.C253

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.