Drouin E, Charpentier F, Gauthier C
Laboratorie de Physiopathologie and Pharmacologie Cellularies and Moleculaires, Hopital G. and R. Laennec, Universite de Nantes, France.
J Cardiovasc Pharmacol. 1996 Mar;27(3):320-6. doi: 10.1097/00005344-199603000-00003.
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).
本研究的目的是评估延长复极化的α1肾上腺素能刺激是否能在雪貂浦肯野纤维中诱发早期后去极化（EADs）。我们使用标准微电极，研究在1.5×10⁻⁶M美托洛尔存在的情况下，10⁻⁶M去氧肾上腺素对从用正常台氏液灌流的离体雪貂浦肯野纤维记录的动作电位（AP）的影响。去氧肾上腺素使复极化60%和90%时的动作电位时程（APD60、APD90）呈时间依赖性延长，在对照期间分别为223±8和269±9毫秒，在灌流1小时后分别为279±11和329±12毫秒（n = 29；两个参数与对照相比p < 0.05），在4小时后分别为334±13和385±15毫秒（n = 29，两个参数与对照和1小时灌流相比p < 0.05），而其他参数未改变。所研究的纤维中约三分之一出现了EADs，可为2相或3相EADs。α1肾上腺素能拮抗剂WB 4101（10⁻⁷M）限制了动作电位的延长并防止了EADs的发生。另一方面，α1肾上腺素能烷基化剂氯乙可乐定（10⁻⁷M）没有作用。钙螯合剂BAPTA [1,2 - 双（2 - 氨基苯氧基）乙烷 - N,N,N',N' - 四乙酸]（2×10⁻³M）虽然抑制了抽搐张力，表明它确实螯合了细胞内钙，但并未阻止去氧肾上腺素诱发EADs。我们的结果表明，α1肾上腺素能刺激可延长雪貂浦肯野纤维的复极化并能诱发EADs。这种作用主要由WB 4101敏感的α1肾上腺素能受体（α1A - 和/或α1C - 肾上腺素能受体）介导，且不依赖于细胞内钙。α1肾上腺素能刺激可能对长QT综合征（LQTS）患者有致心律失常作用。
