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日本鹌鹑工作心肌中的复极化钾电流:心脏电生理学的新型转化模型。

Repolarizing potassium currents in working myocardium of Japanese quail: a novel translational model for cardiac electrophysiology.

机构信息

Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye gory, 1, 12, Moscow 119234, Russia; Laboratory of Cardiac Electrophysiology, National Medical Research Center for Cardiology, 3(rd) Cherepkovskaya str., 15A, Moscow, Russia; Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova str., 1, Moscow, Russia.

Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye gory, 1, 12, Moscow 119234, Russia; Laboratory of Cardiac Electrophysiology, National Medical Research Center for Cardiology, 3(rd) Cherepkovskaya str., 15A, Moscow, Russia; Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova str., 1, Moscow, Russia.

出版信息

Comp Biochem Physiol A Mol Integr Physiol. 2021 May;255:110919. doi: 10.1016/j.cbpa.2021.110919. Epub 2021 Feb 11.

DOI:10.1016/j.cbpa.2021.110919
PMID:33582263
Abstract

Birds developed endothermy and four-chambered high-performance heart independently from mammals. Though avian embryos are extensively studied and widely used as various models for heart research, little is known about cardiac physiology of adult birds. Meanwhile, cardiac electrophysiology is in search for easily accessible and relevant model objects which resemble human myocardium in the pattern of repolarizing currents (I, I, I and I). This study focuses on the configuration of electrical activity and electrophysiological phenotype of working myocardium in adult Japanese quails (Coturnix japonica). The resting membrane potential and action potential (AP) waveform in quail atrial myocardium were similar to that in working myocardium of rodents. Using whole-cell patch clamp and sharp glass microelectrodes, we demonstrated that the repolarization of quail atrial and ventricular myocardium is determined by voltage-dependent potassium currents I, I and I - the latter was previously considered as an exclusive evolutionary feature of mammals. The specific blockers of these currents, dofetilide (3 μmol l), HMR 1556 (30 μmol l) and 4-aminopyridine (3 mmol l), prolonged AP in both ventricular and atrial myocardial preparations. The expression of the corresponding channels responsible for these currents in quail myocardium was investigated with quantitative RT-PCR and western blotting. In conclusion, the described pattern of repolarizing ionic currents and channels in quail myocardium makes this species a novel and suitable experimental model for translational cardiac research and reveals new information related to the evolution of cardiac electrophysiology in vertebrates.

摘要

鸟类独立于哺乳动物进化出了体温调节和四室高性能心脏。尽管鸟类胚胎被广泛研究,并被广泛用作各种心脏研究模型,但成年鸟类的心脏生理学却知之甚少。同时,心脏电生理学正在寻找易于获取的相关模型对象,这些对象在复极化电流(I、I、I 和 I)的模式上类似于人类心肌。本研究聚焦于成年日本鹌鹑(Coturnix japonica)工作心肌的电活动和电生理表型的结构。鹌鹑心房心肌的静息膜电位和动作电位(AP)波形与啮齿动物工作心肌的相似。使用全细胞膜片钳和锋利玻璃微电极,我们证明了鹌鹑心房和心室心肌的复极化由电压依赖性钾电流 I、I 和 I 决定——后者以前被认为是哺乳动物进化的特有特征。这些电流的特异性阻断剂,多非利特(3 μmol l)、HMR 1556(30 μmol l)和 4-氨基吡啶(3 mmol l),延长了心室和心房心肌标本中的 AP。使用定量 RT-PCR 和 Western blot 研究了鹌鹑心肌中负责这些电流的相应通道的表达。总之,鹌鹑心肌中复极化离子电流和通道的描述模式使其成为转化心脏研究的新型和合适的实验模型,并揭示了与脊椎动物心脏电生理学进化相关的新信息。

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