Modulation of Na+-Ca2+ exchange in cardiac sarcolemmal vesicles by Ca2+ antagonists.
The purpose of this study was to examine the effect of three classes of Ca2+ antagonists, diltiazem, verapamil and nifedipine on Na+-Ca2+ exchange mechanism in the sarcolemmal vesicles isolated from canine heart. Na+-Ca2+ exchange and Ca2+ pump (ATP-dependent Ca2+ uptake) activities were assessed using the Millipore filtration technique. Sarcolemmal vesicles used in this study are estimated to consist of several subpopulations wherein 23% are inside-out and 55% are right side-out sealed vesicles in orientation. The affect of each Ca2+ antagonist on the Na+ dependent Ca2+ uptake was studied in the total population of sarcolemmal vesicles, in which none of the agents depressed the initial rate of Ca2+ uptake until concentrations of 10 microM were incubated in the incubation medium. However, when sarcolemmal vesicles were preloaded with Ca2+ via ATP-dependent Ca2+ uptake, cellular Ca2+ influx was depressed only by verapamil (28%) at 1 microM in the efflux medium with 8 mM Na+. Furthermore, inhibition of Ca2+ efflux by verapamil was more pronounced in the presence of 16 mM Na+ in the efflux medium. The order of inhibition was verapamil greater than diltiazem greater than nifedipine. These results indicate that same forms of Ca2+-antagonist drugs may affect the Na+-Ca2+ exchange mechanism in the cardiac sarcolemmal vesicles and therefore we suggest this site of action may contribute to their effects on the myocardium.
Hata
T
T
Department of Bioclimatology and Medicine, Kyushu University, Beppu, Japan.
Makino
N
N
Nakanishi
H
H
Yanaga
T
T
D000255:Adenosine Triphosphate / Q000502:physiology; D000408:Alamethicin / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004073:Digitoxigenin / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D008985:Monensin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004073:Digitoxigenin; D000408:Alamethicin; D010042:Ouabain; D000255:Adenosine Triphosphate; D008985:Monensin; D012964:Sodium; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium