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Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?

Isaac, Emmanuel; Cooper, Stephanie M.; Jones, Sandra A.; Loubani, Mahmoud

Authors

Emmanuel Isaac

Stephanie M. Cooper

Mahmoud Loubani



Abstract

© The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The prevalence of the disease increases with age, strongly implying an age-related process underlying the pathology. At a time when people are living longer than ever before, an exponential increase in disease prevalence is predicted worldwide. Hence unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention strategies. The role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of AF. Nav1.5 is the predominant cardiac isoform, responsible for the action potential upstroke. Recent studies have demonstrated that Nav1.8 (an isoform predominantly expressed within the peripheral nervous system) is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic currents. Animal studies have shown a decline in Nav1.5 leading to a diminished action potential upstroke during phase 0. Furthermore, the study of human tissue demonstrates an inverse expression of sodium channel isoforms; reduction of Nav1.5 and increase of Nav1.8 in both heart failure and ventricular hypertrophy. This strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased heart. Targeting aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging research. This review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence.

Citation

Isaac, E., Cooper, S. M., Jones, S. A., & Loubani, M. (2020). Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?. World Journal of Cardiology, 12(4), 123-135. https://doi.org/10.4330/wjc.v12.i4.123

Journal Article Type Review
Acceptance Date Mar 12, 2020
Publication Date Apr 26, 2020
Deposit Date Nov 6, 2020
Publicly Available Date Nov 6, 2020
Journal World Journal of Cardiology
Electronic ISSN 1949-8462
Publisher Baishideng Publishing Group
Peer Reviewed Peer Reviewed
Volume 12
Issue 4
Pages 123-135
DOI https://doi.org/10.4330/wjc.v12.i4.123
Keywords Voltage-gated; Sodium channels; Ageing; Atrial fibrillation; Nav1.5; Nav1.8; Late sodium current; Cardiac electrophysiology
Public URL https://hull-repository.worktribe.com/output/3595812
Publisher URL https://www.wjgnet.com/1949-8462/full/v12/i4/123.htm

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Publisher Licence URL
http://creativecommons.org/licenses/by-nc/4.0

Copyright Statement
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/





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