Abstract:
: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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Garg P,Garg V,Shrestha R,Sanguinetti MC,Kamp TJ,Wu JCdoi
10.1161/CIRCRESAHA.118.311209subject
Has Abstractpub_date
2018-07-06 00:00:00pages
224-243issue
2eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.118.311209journal_volume
123pub_type
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journal_title:Circulation research
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abstract::In isolated right atria of the rabbit heart, we studied the activation pattern within the sinus node, using the microelectrode technique. After the electrophysiological experiments, the preparations were subjected to a correlative morphological investigation, using light or electron microscopy. Different criteria for ...
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pub_type: 杂志文章
doi:10.1161/01.res.46.6.802
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更新日期:2003-02-07 00:00:00
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