抗心律失常药物（AAD）在治疗病死率极高的心梗后室性心律失常中仍有不可替代的重要地位。生理情况下SCN10A编码的NaV1.8钠通道主要表达于神经元，而心肌组织内以SCN5A编码的NaV1.8钠通道占主导地位。但在心梗等病理状态下在神经元和心肌细胞的NaV1.8表达均有增加/功能增强，使晚钠电流增大，从而参与心律失常的发生和维持。抗心肌缺血药雷诺嗪或可通过阻滞Nav1.8通道、抑制晚钠电流发挥抗心律失常作用。本课题将从分子-细胞-组织-整体四个层次展开研究，观察心梗后神经元形态、细胞因子与神经递质分泌、神经元和心肌细胞内SCN10A表达及功能改变及其对心肌细胞电生理特性的影响和致心律失常机制；以及雷诺嗪和Nav1.8特异性阻滞剂的干预效果。本课题的预期结果有助于进一步理解心梗后室性心律失常的发生机制，并以雷诺嗪的干预效应为借鉴，为研发新型AAD提供思路和实验依据。

Antiarrhythmic drugs (AADs) play very important roles in the treatment of post-myocardial infarction ventricular arrhythmia which has an extremely high mortality. The Nav1.8 sodium channel, encoded by gene SCN10A, usually expressed only in neurons while cardiac sodium channels are dominantly Nav1.5 that is encoded by SCN5A gene. However, under pathological situations like myocardial infarction, expression of Nav1.8 both in neurons and cardiac myocytes will increase; as a consequence will enhance the late sodium current and facilitate the development of ventricular arrhythmia. Ranolazine, an anti-ischemic medication, can exert an anti-arrhythmic effect by blocking the Nav1.8 and inhibiting late sodium current. We hypothesize that post-infarction neural remodeling will lead to an increasing expression of SCN10 in neuronal cells and cardiac myocytes. This study is designed to investigate how these changes will alter electrophysiological properties of ventricular myocardium and its pro-arrhythmic mechanisms. Effects of Ranolazine and specific Nav1.8 inhibitor on the prevention of ventricular arrhythmia will also be studied. It is expected that this study will further our understanding on the mechanism of post-infarction ventricular arrhythmia and provide novel target to develop next generation AADs.