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钠离子通道与相关心脏疾病的研究进展
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Abstract:
电压门控钠离子通道广泛分布于可兴奋细胞的细胞膜上，参与动作电位的产生及传导，主要负责调控动作电位的初始上升相。钠离子通道是最重要的心脏离子通道之一，分布于窦房结、传导系统、心房肌和心室肌，是一类抗心律失常药物的靶蛋白。心脏钠通道的表达正常与否直接影响到心脏的生理病理功能，其功能获得性和功能缺失性的突变均会导致相关心脏疾病的发生。本文阐述了心脏钠离子通道(Nav1.5和Nav1.8)的结构及功能，以及通道异常表达时相关疾病的研究现状，为药物临床应用前的心脏毒性研究及心血管药物的研究开发和临床应用提供重要的理论依据。
Voltage gated sodium channels (VGSCs) are transmembrane proteins responsible for the initial and rapid phase of the action potential in most electrically excitable cells. VGSCs are the most important cardiac ion channels, which are widely located in highly expressed in all types of cardiac myocytes, including the sinus node, the conduction system, atrial and ventricular myocytes. VGSCs are target proteins of type 1 anti-arrhythmic drugs. The expression of cardiac VGSCs may affect the physiological and pathological functions of cardiac. Gain-of-function mutations and loss-of-function mutations of cardiac VGSCs may cause several cardiac diseases. In this article, we focused on reviewing the structure, function and related diseases of cardiac VGSCs (Nav1.5 and Nav1.8), in hopes of providing a reference for further in-depth research regarding relevant drug cardiotoxicity before clinical applications and cardiovascular drug discovery.
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