Evidence that the Na+-Ca2+ exchange system is related to the antiarrhythmic action of disopyramide.
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.
Sakai
Y
Y
2nd Department of Physiology, Showa University, School of Medicine, Tokyo, Japan.
Sekiya
S
S
Inazu
M
M
Homma
I
I
Honda
H
H
Irino
O
O
D000818:Animals; D000889:Anti-Arrhythmia Agents; D002118:Calcium / Q000378:metabolism*; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D066298:In Vitro Techniques; D007474:Ion Exchange; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D012964:Sodium; D004206:Disopyramide; D002118:Calcium