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
Stephanie M. Cooper
Dr Sandra Jones S.A.Jones@hull.ac.uk
Senior Lecturer in Biomedical Science
© 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.
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|
|Publisher||Baishideng Publishing Group|
|Peer Reviewed||Peer Reviewed|
|Keywords||Voltage-gated; Sodium channels; Ageing; Atrial fibrillation; Nav1.5; Nav1.8; Late sodium current; Cardiac electrophysiology|
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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
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