Interaction of some antiarrhythmic drugs with the heart sarcolemmal Na+-Ca2+ exchange system.
The effects of some Class I antiarrhythmics (quinidine, procainamide and lidocaine) and some Class II antiarrhythmics (propranolol, atenolol and acebutolol) on canine cardiac sarcolemmal Na+-Ca2+ exchange activity were studied. Both quinidine (5-100 microM) and procainamide (1-100 microM), unlike lidocaine, inhibited Na+-dependent Ca2+ uptake in sarcolemmal vesicles. The effective concentrations of these agents were well within their respective therapeutic ranges; about 30% inhibition was seen by 10 microM quinidine or procainamide. Propranolol showed a 25% inhibition of the Na+-Ca2+ exchange activity at 100 microM, which concentration is well above its therapeutic range. Acebutolol (0.1-100 microM) had no significant effects, whereas atenolol (10-100 microM), which appeared to inhibit Na+-dependent Ca2+ uptake, also stimulated nonspecific Ca2+ uptake. These results indicate that the cardiac sarcolemmal Na+-Ca2+ exchange system may be one of the sites for the antiarrhythmic actions of quinidine and procainamide.
Eyolfson
D A
DA
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Dhalla
N S
NS
D000070:Acebutolol / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D011342:Procainamide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D001262:Atenolol; D000070:Acebutolol; D008012:Lidocaine; D011433:Propranolol; D011802:Quinidine; D011342:Procainamide; D002118:Calcium