W. Meme et al., CYCLOPIAZONIC ACID-INDUCED CHANGES IN THE CONTRACTION AND CA2-TWITCH SKELETAL-MUSCLE( TRANSIENT OF FROG FAST), American journal of physiology. Cell physiology, 43(1), 1998, pp. 253-261
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.