Inhibitory action of dantrolene sodium on the activation of excitation-contraction coupling in frog skeletal muscle.

Effect of dantrolene sodium on the activation of potassium contracture in single fibers of frog semitendinosus muscle was studied. Dantrolene shifted the activation curve to the right without changing the depolarization produced by a given K+ concentration. The shift of mechanical threshold by dantrolene was dependent on the concentration of calcium in the medium and the effects of dantrolene and Ca++ are additive to each other. On the other hand, the action of dantrolene is antagonized by Ca++ with respect to the peak tension in 190 mM K+. In addition, dantrolene did not release 45Ca from the self-exchangeable Ca fraction and did not affect the exchange of 45Ca in the self-exchangeable Ca fraction with 40Ca. It was also observed that dantrolene had no appreciable influence on the ultrastructure of muscle fibers under our experimental conditions. On the basis of these results, the mechanism of action of dantrolene on the activation of excitation-contraction coupling, the relation between the drug and calcium actions and the drug effect on the Ca movement in T-system membranes were discussed.