ALPHA(1)-ADRENERGIC STIMULATION INDUCES EARLY AFTERDEPOLARIZATIONS INFERRET PURKINJE-FIBERS

The aim of this study was to evaluate whether alpha(1)-adrenergic stim ulation, which prolongs repolarization, could induce early afterdepola rizations (EADs) in ferret Purkinje fibers. We used standard microelec trodes to study the effects of phenylephrine 10(-6)M in the presence o f metoprolol 1.5 x 10(-6)M, on action potentials (AP) recorded from is olated ferret Purkinje fibers superfused with normal Tyrode's solution . Phenylephrine induced a time-dependent prolongation of the AP durati on at 60 and 90% of full repolarization (APD(60), APD(90)) from 223 +/ - 8 and 269 +/- 9 ms, respectively, during control to 279 +/- 11 and 3 29 +/- 12 ms after l-h superfusion (n = 29; p < 0.05 vs. control for b oth parameters) and 334 +/- 13 and 385 +/- 15 ms after 4 h (n = 29, p < 0.05 vs. control and l-h superfusion for both parameters) without ch anging the other parameters. About one third of the fibers studied dev eloped EADs that could be either phase 2 or phase 3 EADs. The alpha(1) -adrenoceptor antagonist WB 4101 (10(-7)M) limited the AP prolongation and prevented the occurrence of EADs. On the other hand, the alpha(1) -adrenoceptor alkylating agent chloroethylclonidine (10(-7)M) had no e ffect. The calcium chelator BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N ',N'-acetic acid] (2 x 10(-3)M) did not prevent the induction of EADs by phenylephrine, although it suppressed the twitch tension, showing t hat it did chelate the intracellular calcium. Our results show that al pha(1)-adrenergic stimulation prolongs repolarization in ferret Purkin je fibers and can induce EADs. This effect is mainly mediated by the W E 4101-sensitive alpha(1)-adrenoceptors (alpha(1A)- and/or alpha(1C)-a drenoceptors) and does not depend on intracellular calcium. alpha(1)-A drenergic stimulation may have arrhythmogenic effects in patients with long QT syndrome (LOTS).