alpha1-adrenergic stimulation induces early afterdepolarizations in ferret Purkinje fibers.
The aim of this study was to evaluate whether alpha1-adrenergic stimulation, which prolongs repolarization, could induce early afterdepolarizations (EADs) in ferret Purkinje fibers. We used standard microelectrodes to study the effects of phenylephrine 10(-6)M in the presence of metoprolol 1.5 x 10(-6)M, on action potentials (AP) recorded from isolated ferret Purkinje fibers superfused with normal Tyrode's solution. Phenylephrine induced a time-dependent prolongation of the AP duration at 60 and 90% of full repolarization (APD60, APD90) from 223 +/- 8 and 269 +/- 9 ms, respectively, during control to 279 +/- 11 and 329 +/- 12 ms after 1-h superfusion (n = 29; p < 0.05 vs. control for both parameters) and 334 +/- 13 and 385 +/- 15 ms after 4 h (n = 29, p < 0.05 vs. control and 1-h superfusion for both parameters) without changing the other parameters. About one third of the fibers studied developed EADs that could be either phase 2 or phase 3 EADs. The alpha1-adrenoceptor antagonist WB 4101 (10(-7)M) limited the AP prolongation and prevented the occurrence of EADs. On the other hand, the alpha1-adrenoceptor alkylating agent chloroethylclonidine (10(-7)M) had no effect. The calcium chelator BAPTA [1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid] (2 x 10(-3)M) did not prevent the induction of EADs by phenylephrine, although it suppressed the twitch tension, showing that it did chelate the intracellular calcium. Our results show that alpha1-adrenergic stimulation prolongs repolarization in ferret Purkinje fibers and can induce EADs. This effect is mainly mediated by the WB 4101-sensitive alpha1-adrenoceptors (alpha1A- and/or alpha1C-adrenoceptors) and does not depend on intracellular calcium. alpha1-Adrenergic stimulation may have arrhythmogenic effects in patients with long QT syndrome (LQTS).
Laboratorie de Physiopathologie and Pharmacologie Cellularies and Moleculaires, Hopital G. and R. Laennec, Universite de Nantes, France.
E
E
Drouin
F
F
Charpentier
C
C
Gauthier
D000818:Animals; D002118:Calcium / Q000502:physiology; D005289:Ferrets; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D002118:Calcium