Action of dantrolene sodium on electrical and mechanical activity of guinea-pig ventricular muscles.
Effects of dantrolene sodium on electrical and mechanical activity of guinea-pig ventricular muscles were examined. The application of 2 X 10(-5) M of dantrolene caused a decrease of developed tension by 31% of the control level without noticeable changes in resting membrane potential, amplitude and maximum upstroke velocity (Vmax) of action potentials, and action potential duration. Negative inotropic effects of dantrolene appeared after 10 min application and reached almost a plateau after 15-20 min. Neither amplitude of the slow inward current nor the outward current on depolarization were affected by dantrolene. When muscle preparations were superfused with the low-K+, high-Ca2+ solution, they developed delayed afterdepolarizations and aftercontractions. The application of 2 X 10(-5) M of dantrolene did not reduce amplitudes of both delayed afterdepolarizations and aftercontractions, but depressed twitch tension to 74% of the control level. Dantrolene did not change the amplitude of the transient inward current observed under the low-K+, high-Ca2+ condition. These results suggest that a primary site of action of dantrolene is not the sarcolemma of ventricular myocardium, but possibly the Ca2+ releasing process from the sarcoplasmic reticulum. Its action is further indicated to affect the process of depolarization-induced Ca2+-release, either directly or indirectly rather than to inhibit Ca2+-induced Ca2+-release.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology*; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles; D007552:Isotonic Solutions / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D013997:Time Factors
D007552:Isotonic Solutions; C037692:Tyrode's solution; D003620:Dantrolene; D011188:Potassium; D002118:Calcium