EFFECTS OF CYCLOPIAZONIC ACID ON CA2-ACTIVATED TENSION PRODUCTION IN SKINNED SKELETAL-MUSCLE FIBERS OF THE FERRET()

The effect of cyclopiazonic acid, an inhibitor of sarcoplasmic reticul um Ca2+-ATPase, was investigated on force generation by the contractil e apparatus in Triton-skinned fibres from extensor digitorum longus an d soleus. Concentrations of cyclopiazonic acid lower than, 10 muM were without effect on Ca2+-activated tension in both types of muscles. In contrast, in soleus, cyclopiazonic acid (20, 50, 100 muM) was found t o shift reversibly the relation-tension pCa (-log[Ca 2+]) towards lowe r free Ca2+ and to decrease maximal Ca2+-activated tension, in a dose- dependent manner. In extensor digitorum longus, the Ca2+ sensitivity w as significantly increased only at a high cyclopiazonic acid concentra tion (100 muM) and for all the concentrations tested between 5 to 100 muM maximal Ca2+-activated tension was unchanged. These results sugges t that cyclopiazonic acid has a direct effect on contractile proteins, in a dose-dependent manner. Ca2+ sensitivity and Ca2+-activated maxim al tension of the contractile apparatus were differentially affected i n fast- (extensor digitorum longus) and slow-twitch (soleus) fibres fr om ferret skeletal muscle.