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Evidence that the Na+-Ca2+ exchange system is related to the antiarrhythmic action of disopyramide
12nd Department of Physiology, Showa University, School of Medicine, Tokyo, Japan.
Abstract:
1. Disopyramide induced a concentration-dependent decrease in action potential amplitude and Vmax, and prolonged action potential durations (APD50 and APD90) in ventricular muscle. 2. Na+-loaded membrane vesicles isolated from canine ventricular muscle rapidly accumulated Ca2+. 3. Monensin (10(-5) M) abolished Na+-dependent Ca2+ uptake, and Na+ enhanced Ca2+ efflux. 4. Na+-Ca2+ exchange by membrane vesicles was more active in preparations pretreated with disopyramide (10(-5) M) than in control membranes. 5. The results suggest that disopyramide changes Na+ influx from Na+ channel mediated to Na+-Ca2+ exchange mediated. This is verified in part by increased Ca2+ efflux.