From the Stanford Cardiovascular Institute (P.G., R.S., J.C.W.).
Department of Medicine, Division of Cardiology (P.G., R.S., J.C.W.).
Circ Res. 2018 Jul 6;123(2):224-243. doi: 10.1161/CIRCRESAHA.118.311209.
Life threatening ventricular arrhythmias leading to sudden cardiac death 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 because of the complexity of the disorder and lack of appropriate cellular and in vivo models. Recent advances in human induced pluripotent stem cell 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 induced pluripotent stem cells 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 human induced pluripotent stem cell-cardiomyocytes 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.
危及生命的室性心律失常导致心源性猝死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，尤其是在年轻人群中，通常是称为离子通道的特殊膜蛋白的遗传缺陷的结果。在心脏中，各种离子通道的异常协调活动介导了心脏动作电位。这些通道的功能或表达的改变会破坏动作电位的构型，导致心脏异常电活动，有时会引发心律失常。由于疾病的复杂性和缺乏适当的细胞和体内模型，理解遗传性心律失常的病理生理学可能具有挑战性。人类诱导多能干细胞技术的最新进展通过在体外的培养皿中模拟这些复杂的心律失常综合征，在理解离子通道紊乱或通道病的潜在机制方面取得了显著进展。为了充分发挥诱导多能干细胞在阐明通道病的机制基础和复杂病理生理学方面的潜力，了解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中的作用以及心律失常的分子和细胞机制，强调人类诱导多能干细胞-心肌细胞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。总的来说，这篇综述旨在为心脏电活动和相关通道病提供基本的理解，特别是为心血管领域的临床医生或研究科学家提供，他们对电生理学背景的了解有限。
