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就电生理特性而言,犬类心肌细胞是人类心室细胞的良好模型。

Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties.

作者信息

Nánási Péter P, Horváth Balázs, Tar Fábián, Almássy János, Szentandrássy Norbert, Jost Norbert, Baczkó István, Bányász Tamás, Varró András

机构信息

Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary.

出版信息

Pharmaceuticals (Basel). 2021 Jul 29;14(8):748. doi: 10.3390/ph14080748.

Abstract

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca current (I), late Na current (I), rapid and slow components of the delayed rectifier K current (I and I, respectively), inward rectifier K current (I), transient outward K current (I), and Na/Ca exchange current (I) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of I and the recovery kinetics of I. I displayed a largely four-fold larger density in canine than human myocytes, and I recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger I, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

摘要

由于健康人体心室组织的获取有限,因此必须应用最合适的动物模型进行电生理和药理学研究。通过研究常用实验动物(如狗、兔子、豚鼠或大鼠)中形成动作电位的离子电流特性,并将其与人类心肌细胞的特性进行比较,可最好地确定这种动物模型。本文作者拥有在哺乳动物和人体心室组织以及分离的心肌细胞中进行三十年电生理研究的经验,总结了他们在主要犬类和人类心脏离子电流方面获得的结果。相应地,对L型钙电流(I)、晚钠电流(I)、延迟整流钾电流的快速和慢速成分(分别为I和I)、内向整流钾电流(I)、瞬时外向钾电流(I)以及钠/钙交换电流(I)进行了表征和比较。重要的是,其中许多测量是使用动作电位电压钳技术进行的,该技术可使心室动作电位期间实际流动的电流分布可视化。除了I的密度和I的恢复动力学外,这些离子电流的密度和形状以及动作电位形态在人类和犬类心室细胞中相似。犬类心肌细胞中I的密度比人类心肌细胞大得多,大约是四倍,并且两种物种中I从失活状态的恢复表现出略有不同的时间进程。基于这些结果,可以得出结论,犬类心室细胞代表了用于电生理研究的人类心肌细胞的合理良好模型,但是,必须记住,由于它们具有更强的I,犬类细胞中的复极储备更为明显,并且还可以预期频率依赖性复极模式存在适度差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/725b/8398821/68eec312235f/pharmaceuticals-14-00748-g001.jpg

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