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成年斑马鱼心脏可作为人类心脏模型?一项电生理学研究。

Adult zebrafish heart as a model for human heart? An electrophysiological study.

机构信息

Biotechnology Center and Center for Regenerative Therapies, Dresden University of Technology, Dresden, Germany.

出版信息

J Mol Cell Cardiol. 2010 Jan;48(1):161-71. doi: 10.1016/j.yjmcc.2009.08.034. Epub 2009 Sep 8.

DOI:10.1016/j.yjmcc.2009.08.034
PMID:19747484
Abstract

The zebrafish has recently emerged as an excellent model for studies of heart development and regeneration. The physiology of the zebrafish heart has been suggested to resemble that of the human heart in many aspects, whereas, in contrast to mammals, the zebrafish has a remarkable ability to regenerate after heart injury. Thus, zebrafish have been proposed as a cost-effective model for genetic and pharmacological screens of factors affecting heart function and repair. However, realizing the full potential of the zebrafish heart as a model will require a better understanding of the electrophysiology of the adult zebrafish myocardium. Here, we characterize action potentials (APs) from intact adult atria and ventricles and find that the overall shape of zebrafish APs is similar to that of humans. We show that zebrafish, like most mammals, display functional acetylcholine-activated K(+) channels in the atrium, but not in the ventricle. Furthermore, the zebrafish AP upstroke is dominated by Na(+) channels, L-type Ca(2+) channels contribute to the plateau phase and I(Kr) channels are involved in repolarization. However, despite these similarities between zebrafish and mammalian electrophysiology, we also identified important differences. In particular, zebrafish display a robust T-type Ca(2+) current in both atrial and ventricular cardiomyocytes. Interestingly, in most mammals T-type Ca(2+) channels are only expressed in the developing heart or under pathophysiological conditions, indicating that adult zebrafish cardiomyocytes display a more immature phenotype.

摘要

斑马鱼最近已成为研究心脏发育和再生的优秀模型。在许多方面,斑马鱼的心脏生理学被认为与人类心脏相似,而与哺乳动物不同的是,斑马鱼在心脏受伤后具有显著的再生能力。因此,斑马鱼被提议作为一种具有成本效益的模型,用于筛选影响心脏功能和修复的遗传和药理学因素。然而,要充分发挥斑马鱼心脏作为模型的潜力,需要更好地了解成年斑马鱼心肌的电生理学。在这里,我们描述了完整的成年心房和心室的动作电位(APs),并发现斑马鱼 APs 的整体形状与人类相似。我们表明,像大多数哺乳动物一样,斑马鱼在心房中显示出功能性的乙酰胆碱激活的 K(+)通道,但在心室中没有。此外,斑马鱼的 AP 上升主要由 Na(+)通道主导,L 型 Ca(2+)通道有助于平台期,I(Kr)通道参与复极化。然而,尽管斑马鱼和哺乳动物的电生理学有这些相似之处,我们也发现了一些重要的差异。特别是,斑马鱼在心房和心室心肌细胞中都显示出强大的 T 型 Ca(2+)电流。有趣的是,在大多数哺乳动物中,T 型 Ca(2+)通道仅在发育中的心脏或病理生理条件下表达,这表明成年斑马鱼心肌细胞表现出更不成熟的表型。

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