Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as Models for Cardiac Channelopathies: A Primer for Non-Electrophysiologists.
Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as Models for Cardiac Channelopathies: A Primer for Non-Electrophysiologists.
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DOI：
10.1161/circresaha.118.311209
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发表时间：
2018-07-06
影响因子：
20.1
通讯作者：
Wu JC
中科院分区：
文献类型：
--
作者：
Garg P;Garg V;Shrestha R;Sanguinetti MC;Kamp TJ;Wu JC
导致心脏性猝死（SCD）的危及生命的室性心律失常是发病率和死亡率的主要原因。在没有结构性心脏病的情况下，这些心律失常，特别是在年轻人群中，通常是称为“离子通道”的专门膜蛋白遗传缺陷的结果。在心脏中，各种离子通道的活动异常协调，介导心脏动作电位。这些通道的功能或表达的改变可以破坏动作电位的配置，导致心脏的异常电活动，有时可以引发心律失常。了解遗传性心律失常的病理生理学可能是具有挑战性的，由于疾病的复杂性和缺乏适当的细胞和体内模型。人类诱导多能干细胞（hiPSC）技术的最新进展通过在培养皿中体外模拟这些复杂的心律失常综合征，在理解离子通道障碍或“通道病”的潜在机制方面提供了显著进展。为了充分认识iPSC在阐明通道病的机制基础和复杂病理生理学方面的潜力，掌握心肌细胞电生理学的基本知识至关重要。在这篇综述中，我们将讨论各种离子通道在心脏电生理学和心律失常的分子和细胞机制中的作用，强调hiPSC-CM作为研究遗传性心律失常综合征和测试抗心律失常策略的模型的前景。总体而言，本文旨在提供对心脏电活动和相关通道病变的基本了解，特别是对于电生理学背景有限的心血管领域的临床医生或研究科学家。
Life threatening ventricular arrhythmias leading to sudden cardiac death (SCD) are a major cause of morbidity and mortality. In the absence of structural heart disease, these arrhythmias, especially in the younger population are often an outcome of genetic defects in specialized membrane proteins called ‘ion channels’. In the heart, exceptionally well-orchestrated activity of a diversity of ion channels mediates the cardiac action potential. Alterations in either the function or expression of these channels can disrupt the configuration of the action potential, leading to abnormal electrical activity of the heart that can sometimes initiate an arrhythmia. Understanding the pathophysiology of inherited arrhythmias can be challenging due to the complexity of the disorder and lack of appropriate cellular and in vivo models. Recent advances in human induced pluripotent stem cell (hiPSC) technology have provided remarkable progress in comprehending the underlying mechanisms of ion channel disorders or ‘channelopathies’ by modeling these complex arrhythmia syndromes in vitro in a dish. To fully realize the potential of iPSCs in elucidating the mechanistic basis and complex pathophysiology of channelopathies, it is crucial to have a basic knowledge of cardiac myocyte electrophysiology. In this review, we will discuss the role of the various ion channels in cardiac electrophysiology and the molecular and cellular mechanisms of arrhythmias, highlighting the promise of hiPSC-CMs as a model for investigating inherited arrhythmia syndromes and testing antiarrhythmic strategies. Overall, this review aims to provide a basic understanding of the electrical activity of the heart and related channelopathies, especially to clinicians or research scientists in the cardiovascular field with limited electrophysiology background.