Effects of dantrolene sodium on the excitation-contraction coupling of the mammalian and amphibian cardiac muscle

Abstract

Dantrolene sodium at concentrations which inhibit the twitch tension of frog toe muscle and is without effect on resting and action potentials exhibited a positive inotropic action in mammalian and amphibian myocardium. In guinea-pig atrial muscle, twitch tension was initially decreased and thereafter gradually increased above the control. In frog atrial muscle, twitch tension was potentiated by dantrolene sodium without a prior phase of decreased tension. In both guinea-pig and frog atrial muscles, the action potential duration was prolonged by the drug. The amplitude of the slow response was augmented by dantrolene sodium in guinea-pig and frog atria that were partially depolarized by KCl. These results suggest that dantrolene sodium increases the slow inward Ca current which consequently potentiates the twitch tension. The transient decrease of twitch tension in the guinea-pig atrial muscle could be due to inhibition of calcium release from the sarcoplasmic reticulum as postulated for skeletal muscle. The possibilities that the drug acts either on the Ca permeability of the membrane of the sarcoplasmic reticulum or on the junctional portion between the sarcolemma and the subsarcolemmal cisternae are discussed.