MECHANISMS UNDERLYING EARLY AND DELAYED AFTERDEPOLARIZATIONS INDUCED BY CATECHOLAMINES
MECHANISMS UNDERLYING EARLY AND DELAYED AFTERDEPOLARIZATIONS INDUCED BY CATECHOLAMINES
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DOI：
10.1152/ajpheart.1990.258.6.h1796
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发表时间：
1990-06-01
影响因子：
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通讯作者：
CORR, PB
中科院分区：
文献类型：
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作者：
PRIORI, SG;CORR, PB
利用分离的成年犬心室肌细胞的细胞内微电极记录，评估α -和β -肾上腺素能受体激活对去极化后诱发早期（EADs）和延迟（DADs）的相对影响。在不同频率（0.5- 4hz）起搏期间，常氧肌细胞暴露于α -肾上腺素激动剂苯肾上腺素(10（-8)-10(-6)M）或β -肾上腺素激动剂异丙肾上腺素(10（-9)-10(-6)M）。肾上腺素能刺激导致动作电位持续时间呈剂量依赖性延长，但不能诱导EADs或DADs。低浓度(10（-9)-10(-8)M）异丙肾上腺素刺激β -肾上腺素能导致动作电位延长，而高浓度（10（-7）和10(-6)M）导致动作电位明显缩短。异丙肾上腺素在10（-8）至10(-6)M的浓度范围内引起单个或多个（2-5）DADs，随着细胞速度的增加，dad的振幅相应增加，偶联间隔缩短。DADs经常启动并维持持续触发的节律，这些节律自然终止。异丙肾上腺素(10（-8)-10(-6)M）在最高浓度（10(-6)M）和中等起搏频率（1-2 Hz）下也能在80%的细胞中引起EADs。EADs通常以2:1或3:1的模式发生。异丙肾上腺素诱导的EADs和DADs被低细胞外钠、ryanodine （10(-6) M）或benzamil （10(-4) M）可逆地消除，从而表明肌浆网Ca2+释放和细胞外Na+浓度是两种类型后去极化发展的两个主要因素。心室肌异丙肾上腺素可诱发EADs，这表明β -肾上腺素能受体介导完整心脏心律失常的新途径。
The relative influence of alpha- and beta-adrenergic receptor activation in eliciting early (EADs) and delayed (DADs) after depolarizations was assessed using intracellular microelectrode recordings in isolated adult canine ventricular myocytes. Normoxic myocytes were exposed to the alpha-adrenergic agonist phenylephrine (10(-8)-10(-6) M) or the beta-adrenergic agonist isoproterenol (10(-9)-10(-6) M) during pacing at different frequencies (0.5-4 Hz). alpha-Adrenergic stimulation resulted in a dose-dependent prolongation of action potential duration but failed to induce either EADs or DADs. beta-Adrenergic stimulation with isoproterenol at low concentrations (10(-9)-10(-8) M) induced a prolongation of the action potential, whereas higher concentrations (10(-7) and 10(-6) M) resulted in a marked shortening. Isoproterenol elicited single or multiple (2-5) DADs at concentrations from 10(-8) to 10(-6) M, with a corresponding increase in the amplitude of the DADs and decrease in the coupling interval as cells were paced at increasing rates. DADs often initiated and maintained sustained triggered rhythms that spontaneously terminated. Isoproterenol (10(-8)-10(-6) M) also elicited EADs in 80% of cells at the highest concentration utilized (10(-6) M) and at intermediate pacing frequencies (1-2 Hz). EADs often occurred with a 2:1 or 3:1 pattern. EADs and DADs induced by isoproterenol were reversibly abolished by low extracellular sodium, ryanodine (10(-6) M), or benzamil (10(-4) M), thus indicating that Ca2+ release from the sarcoplasmic reticulum and extracellular Na+ concentration are two major factors in the development of both types of afterdepolarizations. The demonstration that EADs can be induced by isoproterenol in ventricular muscle suggest a novel pathway for beta-adrenergic receptors to mediate arrhythmogenesis in the intact heart.