Modification of cardiac sarcolemmal Na+-Ca2+ exchange by diltiazem and verapamil.
Cardiac sarcolemmal membranes were isolated from the rat heart and their ability for Na+-Ca2+ exchange in the absence or presence of diltiazem and verapamil was examined. Maximal Ca2+ influx activity of membranes due to Na+-dependent reaction occurred within 3 min and was about 5 nmol Ca2+/mg protein. Diltiazem (0.1 to 10 microM) depressed the Ca2+ influx activity significantly whereas verapamil (0.1 to 10 microM) had no effect at initial stages of the reaction (10 to 20 sec). The inhibitory effect of diltiazem on Ca2+ influx was found to be of an uncompetitive nature. Sodium was found to cause a rapid Ca2+ efflux from the calcium loaded membrane vesicles; about 70% of the Ca2+ efflux activity was increased by 0.1 to 10 microM of verapamil and 10 microM of diltiazem significantly. The stimulatory effect of these agents on Ca2+ efflux was associated with a change in Ka value from 16 to 5 mM Na+. Both diltiazem (0.1-3 microM) and verapamil (0.1-10 microM) did not affect the membrane Na+-K+ ATPase activity, but diltiazem in high concentrations (10-30 microM) had an inhibitory action. Specific calcium channel blocking agents, nitrendipine and nifedipine, depressed sodium-dependent Ca2+-efflux activity. A beta-adrenoreceptor antagonist, propranolol, unlike acebutolol, increased sodium-induced Ca2+-influx at high concentrations (10-100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
D000070:Acebutolol / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
D001552:Benzazepines; D000070:Acebutolol; D009568:Nitrendipine; D012964:Sodium; D011433:Propranolol; D014700:Verapamil; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium