Department of Human and Animal Physiology, Lomonosov Moscow State University, Moscow, Russia.
Department of Physiology, Pirogov Russian National Research Medical University, Moscow, Russia.
Acta Physiol (Oxf). 2021 Apr;231(4):e13597. doi: 10.1111/apha.13597. Epub 2020 Dec 20.
This study is aimed at investigation of electrophysiological effects of α1-adrenoreceptor (α1-AR) stimulation in the rat superior vena cava (SVC) myocardium, which is one of the sources of proarrhythmic activity.
α1-ARs agonists (phenylephrine-PHE or norepinephrine in presence of atenolol-NE + ATL) were applied to SVC and atrial tissue preparations or isolated cardiomyocytes, which were examined using optical mapping, glass microelectrodes or whole-cell patch clamp. α1-ARs distribution was evaluated using immunofluorescence. Kir2.X mRNA and protein level were estimated using RT-PCR and Western blotting.
PHE or NE + ATL application caused a significant suppression of the conduction velocity (CV) of excitation and inexcitability in SVC, an increase in the duration of electrically evoked action potentials (APs), a decrease in the maximum upstroke velocity (dV/dt ) and depolarization of the resting membrane potential (RMP) in SVC to a greater extent than in atria. The effects induced by α1-ARs activation in SVC were attenuated by protein kinase C inhibition (PKC). The whole-cell patch clamp revealed PHE-induced suppression of outward component of I inward rectifier current in isolated SVC, but not atrial myocytes. These effects can be mediated by α1A subtype of α-ARs found in abundance in rat SVC. The basal I level in SVC was much lower than in atria as a result of the weaker expression of Kir2.2 channels.
Therefore, the reduced density of I in rat SVC cardiomyocytes and sensitivity of this current to α1A-AR stimulation via PKC-dependent pathways might lead to proarrhythmic conduction in SVC myocardium by inducing RMP depolarization, AP prolongation, CV and dV/dt decrease.
本研究旨在探讨大鼠上腔静脉（SVC）心肌中α1-肾上腺素能受体（α1-AR）刺激的电生理效应，SVC 是致心律失常活动的来源之一。
用光学映射、玻璃微电极或全细胞膜片钳技术，将α1-AR 激动剂（苯肾上腺素-PHE 或在阿替洛尔-NE+ATL 存在下的去甲肾上腺素-NE+ATL）应用于 SVC 和心房组织标本或分离的心肌细胞，以评估α1-AR 分布。采用 RT-PCR 和 Western blot 法检测 Kir2.X mRNA 和蛋白水平。
PHE 或 NE+ATL 应用可显著抑制 SVC 的兴奋和不应期的传导速度（CV），延长电诱发动作电位（AP）的持续时间，降低 SVC 的最大上升速度（dV/dt），使静息膜电位（RMP）去极化，其程度大于心房。SVC 中α1-AR 激活引起的作用可被蛋白激酶 C 抑制（PKC）减弱。全细胞膜片钳显示 PHE 诱导的 SVC 分离心肌细胞内向整流电流外向成分抑制，但心房心肌细胞没有。这些作用可由大鼠 SVC 中丰富的α1A 亚型的α-AR 介导。由于 Kir2.2 通道表达较弱，SVC 的基础 I 水平远低于心房。
因此，大鼠 SVC 心肌细胞中 I 的密度降低，以及该电流对 PKC 依赖途径的α1A-AR 刺激的敏感性，可能通过引起 RMP 去极化、AP 延长、CV 和 dV/dt 降低，导致 SVC 心肌的致心律失常传导。
