Effect of dantrolene sodium on the transmembrane potentials and contractility of guinea pig atrial myocardium.

Dantrolene sodium (3 X 10(-4) M) exerted a biphasic effect on the mechanical and electrical activity of the isolated guinea pig left atrium. In the first phase, the drug increased the contractile force by about 200%, and prolonged the action potential duration. This transient positive inotropic effect was antagonized by D-600, a slow Ca2+ channel inhibitor. In the later phase, the drug gradually decreased the amplitude of contractions, shortened the action potential duration and induced contracture. Dantrolene sodium increased the rate of depolarization and overshoot of Ca2+ -mediated slow action potentials. The results suggest that dantrolene sodium increases the slow inward Ca2+ current, causing a positive inotropic effect in the atrial myocardium. The late negative inotropic effect of the drug could be due to a secondary inhibition of the slow inward Ca2+ current due to an increased intracellular free Ca2+ concentration as a consequence of other actions of the drug.