钠通道阻滞剂（SCB）用于治疗心房颤动（AF）时的潜在致室性心律失常效应严重限制了其临床应用。心房/心室肌细胞在钠通道动力学上的差异性为研究和利用"心房选择性"SCB治疗AF提供了理论基础。本课题突破前人研究模式，在犬心房/心室肌细胞、人TiPSCs诱导分化的心房/心室肌细胞以及人心房肌细胞上分别观察不同SCB对钠通道动力学的影响，进而在犬心房/心室肌组织和整体动物模型上比较不同SCB对心房/心室肌电生理特性的影响，探讨各种SCB对心房肌细胞钠通道抑制的"选择性"程度与其抗AF效能和安全性之间的关系，并依此筛选最佳的药物。本研究拟从"细胞-组织-整体"三个层次阐明"心房选择性"SCB在治疗AF中的地位和机制，并利用人TiPSCs诱导分化的及人的心肌细胞为实验对象以获得最接近人体的研究结果。本课题为抗心律失常药物研究开辟了一个全新领域，将有力推进"心房选择性"SCB这一AF治疗新策略的应用。

Applying a sodium channel blocker for the management of atrial fibrillation is limited by the pro-arrhythmic effect of the medication. Recent studies have revealed the electrophysiological heterogeneity between the atrial and ventricular cardiac myocytes from the aspect of the ion kinetics of transmural sodium channel.In light of this, we design this study to investigate the "atrial selectivity" of sodium channel block by different drugs, including conventional Class I antiarrhythmic drugs, Ranolazine, and some Chinese herb extrudates. We will be using atrial and ventricular cardiac myocytes isolated from canine myocardium or derived from human T lymphocytes-induced pluripotent stem cells (TiPSCs) as our experimental subjects, as well as the human atrial myocytes collected during open heart surgeries. Patch clamp technique will be used to test the sodium channel kinetics after pre-treating the cells with different regimens and the results will be compared between atrial and ventricular myocytes, in order to determine the "selectivity" of sodium channel blockage by these drugs. We will also develop a canine myocardial wedge model consisting of atrial and ventricular cardiac muscles and conduct experiments in dogs in vivo. The "atrial selective effect" of the medications and their significance in the suppression or induction of atrial fibrillation will be explored. The present study, utilizing several cutting-edge techniques, will help us further understanding the efficacy and safety of different sodium channel blockers, among which those with the highest "atrial selectivity" should demonstrate abilities of suppressing atrial arrhythmias with minimum effects on the ventricular myocardium. "Selectively" blocking the sodium channel of the atrial myocardium is a novel target of pharmacological treatment of atrial fibrillation.