Calcium current depression in isolated human atrial myocytes after cessation of chronic treatment with calcium antagonists.
The present study investigates the possibility that the slow calcium current of human atrial cardiac cells is modified by chronic treatment (1-24 months) with calcium antagonists (nifedipine, nicardipine, or diltiazem) in a manner different from a simple drug-induced blocking effect. Data from treated patients were recorded approximately 30 hours after cessation of the treatment and were compared with those of nontreated patients. In the treated group, the action potential plateau of atrial fibers was always markedly and irreversibly depressed, and action potential duration measured at 50% repolarization was markedly shortened (81 +/- 12 msec, n = 13) compared with normal values (155 +/- 9 msec, n = 28). In isolated atrial cells, peak calcium current density at +10 mV in treated cells was more than three times as small as that in nontreated cells. Steady-state inactivation relations of calcium current as a function of membrane potential were not significantly different in treated and nontreated cells. In contrast, in treated and nontreated cells superfused with 10(-6) M nifedipine, the curves were markedly shifted toward negative potentials. Cell superfusion with 10(-6) M Bay K 8644 increased calcium current to a larger extent in nontreated cells (sixfold increase) than in treated cells (threefold increase), whereas a 23-fold increase was observed in nontreated cells in which the current had been previously depressed by superfusion with 10(-6) M nifedipine. In contrast to Bay K 8644, 10(-7) M isoproterenol and 10(-8) M angiotensin II increased the calcium current to the same extent in both treated and nontreated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Le Grand
B
B
Laboratoire de Physiologie Comparée, Université Paris XI, Orsay, France.
Hatem
S
S
Deroubaix
E
E
Couetil
J P
JP
Coraboeuf
E
E
D000200:Action Potentials; D016275:Atrial Function; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006325:Heart Atria / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D013997:Time Factors
D002121:Calcium Channel Blockers; D002118:Calcium