Lee J H, Rosen M R
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Cardiovasc Res. 1993 May;27(5):839-44. doi: 10.1093/cvr/27.5.839.
The aim was to evaluate the role of alpha 1 adrenoceptor stimulation and selective receptor subtype blockade on delayed afterdepolarisations induced by high extracellular calcium ([Ca2+]o = 8.1 mM) and by ouabain (2 x 10(-7) M) in canine Purkinje fibres.
Standard microelectrode techniques were used to record transmembrane action potentials from Purkinje fibres placed at cycle length = 500 ms. The drive was interrupted for 5 s every minute to allow observation of delayed afterdepolarisations or any subsequent spontaneous rhythms.
The alpha 1 adrenoceptor agonist phenylephrine, 1 x 10(-7) M, increased the amplitude of delayed afterdepolarisations induced by high [Ca] from 4.2(SEM 0.4) to 5.4(0.2) mV (p < 0.05), and by ouabain from 4.3(0.6) to 6.9(1.0) mV (p < 0.05). The selective alpha 1 adrenoceptor subtype agonist WB 4101, 1 x 10(-7) M, blocked the effect of phenylephrine on delayed afterdepolarisations induced by ouabain + phenylephrine [DAD = 4.6(0.6), p < 0.05] but decreased the amplitude of those induced by Ca + phenylephrine, to 2.0(0.3) mV (p < 0.05). In contrast, the selective alpha 1b adrenoceptor antagonist chloroethylclonidine, 1 x 10(-7) M, increased the amplitude of delayed afterdepolarisations induced by Ca and phenylephrine to 6.6(0.6) mV (p < 0.05) and by ouabain and phenylephrine to 12.6(2.0) mV (p < 0.05).
alpha 1 Adrenoceptor subtypes modulate the amplitude of delayed afterdepolarisations induced by ouabain and by high [Ca]. The chloroethylclonidine-blocked alpha 1 adrenoceptor subtype decreases, and the WB 4101-blocked subtype potentiates, this arrhythmogenic mechanism.
旨在评估α1肾上腺素能受体刺激和选择性受体亚型阻断对高细胞外钙（[Ca2+]o = 8.1 mM）和哇巴因（2×10−7 M）诱导的犬浦肯野纤维延迟后去极化的作用。
采用标准微电极技术记录周期长度为500 ms时浦肯野纤维的跨膜动作电位。每分钟中断驱动5秒，以观察延迟后去极化或任何随后的自发节律。
α1肾上腺素能受体激动剂去氧肾上腺素，1×10−7 M，使高钙诱导的延迟后去极化幅度从4.2（标准误0.4）mV增加到5.4（0.2）mV（p < 0.05），使哇巴因诱导的延迟后去极化幅度从4.3（0.6）mV增加到6.9（1.0）mV（p < 0.05）。选择性α1肾上腺素能受体亚型激动剂WB 4101，1×10−7 M，阻断了去氧肾上腺素对哇巴因 + 去氧肾上腺素诱导的延迟后去极化的作用[延迟后去极化 = 4.6（0.6），p < 0.05]，但将钙 + 去氧肾上腺素诱导的延迟后去极化幅度降低到2.0（0.3）mV（p < 0.05）。相反，选择性α1b肾上腺素能受体拮抗剂氯乙可乐定，1×10−7 M，使钙和去氧肾上腺素诱导的延迟后去极化幅度增加到6.6（0.6）mV（p < 0.05），使哇巴因和去氧肾上腺素诱导的延迟后去极化幅度增加到12.6（2.0）mV（p < 0.05）。
α1肾上腺素能受体亚型调节哇巴因和高钙诱导的延迟后去极化幅度。氯乙可乐定阻断的α1肾上腺素能受体亚型降低了这种致心律失常机制，而WB 4101阻断的亚型则增强了这种机制。
