Isaac Emmanuel, Cooper Stephanie M, Jones Sandra A, Loubani Mahmoud
Department of Cardiothoracic Surgery, Hull University Teaching Hospitals, Cottingham HU16 5JQ, United Kingdom.
Department of Biomedical Sciences, University of Hull, Hull HU6 7RX, United Kingdom.
World J Cardiol. 2020 Apr 26;12(4):123-135. doi: 10.4330/wjc.v12.i4.123.
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. Na1.5 is the predominant cardiac isoform, responsible for the action potential upstroke. Recent studies have demonstrated that Na1.8 (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 Na1.5 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 Na1.5 and increase of Na1.8 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.
心房颤动（AF）是全球最常见的心律失常。该疾病的患病率随年龄增长而增加，强烈暗示其病理过程与年龄相关。在人们寿命比以往任何时候都更长的时代，预计全球疾病患病率将呈指数增长。因此，揭示该疾病的潜在机制对于开发创新的治疗和预防策略至关重要。电压门控钠通道的作用在心脏电生理学中至关重要，可能为房颤的心律失常发生机制提供新的见解。Na1.5是主要的心脏亚型，负责动作电位的上升支。最近的研究表明，Na1.8（一种主要在外周神经系统表达的亚型）通过增强促心律失常电流导致细胞心律失常。动物研究表明，Na1.5减少导致0期动作电位上升支减弱。此外，对人体组织的研究表明钠通道亚型的表达呈相反趋势；在心力衰竭和心室肥厚中，Na1.5减少而Na1.8增加。这强烈表明电压门控钠通道的表达在患病心脏心律失常的发生中起关键作用。针对异常钠电流已产生了治疗房颤的新方法，并且仍然是一个新兴的研究领域。本综述将通过研究基于实验室和临床的证据，探讨电压门控钠通道如何使老年心脏易患房颤。
