Effect of dantrolene sodium on the mechanical and electrical properties of guinea-pig ventricular myocardium.

The effect of dantrolene sodium on transmembrane potential and contractile force was examined in electrically driven right ventricular papillary muscles of guinea-pigs. Dantrolene sodium (2 x 10(-4) M) shortened the action potential and increased overshoot and the maximum rate of depolarization (Vmax), without changing the resting potential. Contractile force was increased by the drug. The dantrolene sodium-induced changes could be antagonized with pindolol, a beta-adrenoceptor blocker. Dantrolene sodium exerted a negative inotropic effect in papillary muscles of guinea-pigs pretreated with reserpine. The drug increased the amplitude and Vmax of slow action potentials. Pindolol was able to abolish this action. The results suggest that the positive inotropic effect of dantrolene sodium may be due to catecholamine release, whereas the drug has a negative inotropic effect by itself.