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Cardiac Arrhythmias Related to Sodium Channel Dysfunction

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Voltage-gated Sodium Channels: Structure, Function and Channelopathies

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 246))

Abstract

The voltage-gated cardiac sodium channel (Nav1.5) is a mega-complex comprised of a pore-forming α subunit and 4 ancillary β-subunits together with numerous protein partners. Genetic defects in the form of rare variants in one or more sodium channel-related genes can cause a loss- or gain-of-function of sodium channel current (INa) leading to the manifestation of various disease phenotypes, including Brugada syndrome, long QT syndrome, progressive cardiac conduction disease, sick sinus syndrome, multifocal ectopic Purkinje-related premature contractions, and atrial fibrillation. Some sodium channelopathies have also been shown to be responsible for sudden infant death syndrome (SIDS). Although these genetic defects often present as pure electrical diseases, recent studies point to a contribution of structural abnormalities to the electrocardiographic and arrhythmic manifestation in some cases, such as dilated cardiomyopathy. The same rare variants in SCN5A or related genes may present with different clinical phenotypes in different individuals and sometimes in members of the same family. Genetic background and epigenetic and environmental factors contribute to the expression of these overlap syndromes. Our goal in this chapter is to review and discuss what is known about the clinical phenotype and genotype of each cardiac sodium channelopathy, and to briefly discuss the underlying mechanisms.

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Supported by NIH grant HL47678 (CA) and the Wistar and Martha Morris Fund (CA).

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  1. Lankenau Institute for Medical Research, 100 E. Lancaster Avenue, Wynnewood, PA, 19096, USA

    Eleonora Savio-Galimberti, Mariana Argenziano & Charles Antzelevitch

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  1. Eleonora Savio-Galimberti
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  1. CERVO Brain Research Center, Institut Universitaire en Santé Mentale, Quebec, Canada

    Mohamed Chahine

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Savio-Galimberti, E., Argenziano, M., Antzelevitch, C. (2017). Cardiac Arrhythmias Related to Sodium Channel Dysfunction. In: Chahine, M. (eds) Voltage-gated Sodium Channels: Structure, Function and Channelopathies. Handbook of Experimental Pharmacology, vol 246. Springer, Cham. https://doi.org/10.1007/164_2017_43

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