[Electrophysiologic and intropic effects of dantrolene on isolated ventricular myocardium. Studies on guinea pig papillary muscle]

Abstract

The effect of dantrolene (D) on transmembrane potential and contractile force was examined in electrically driven right ventricular papillary muscles of guinea-pigs. Independent of stimulation frequency D (100 mumol/l) caused a significant reduction of contractility by ca. 40% from control levels. Action potential duration measured at the 90% and 50% repolarisation level was significantly increased while plateau phase was slightly depressed by D. Resting membrane potential, action potential amplitude and maximum rate of depolarisation in phase 0 were unaffected. The effect of D on action potential duration was significantly dependent upon the frequency of stimulation. At faster rates action potential duration was increased relatively more than at slower rates. Slow response action potentials were unaffected by D. Unlike Ryanodine D did not flatten the force-frequency-relationship curve and did not influence the force-interval-relationship under extrastimulation. - It is concluded that the direct negative inotropic effect of D is not accompanied by a transsarcolemmal influence such as an inhibition of fast Na+- or slow Ca++-channels. The results are compatible with an intracellular site of action of D as postulated for skeletal muscle. D acts differently from ryanodine, another presumed inhibitor of sarcoplasmic reticulum.