心肌缺血和心肌梗死时发生的室性心律失常与静息电位(RP)减小和内向整流钾电流（IK1）下降有关，但目前临床应用的抗心律失常药物没有一个是以激动IK1和（或）增大RP而发挥作用的。由此设想适度增强IK1，进而增大或恢复RP，可以预防或治疗缺血性心律失常。我们发现并报道了首个IK1选择性激动剂zacopride。本课题将通过结扎大鼠冠状动脉致急性缺血和慢性心梗模型，检验zacopride抗缺血性心律失常的效应；利用膜片钳技术观察缺氧条件下zacopride对大鼠心室肌细胞IK1及RP的影响；观察它对HEK293细胞转染Kir2.x通道的作用，明确介导zacopride调节IK1的Kir2.x通道类型；利用Real Time PCR和免疫印迹法分析其对急性模拟缺血和慢性缺血心肌IK1/Kir2.x 通道mRNA和蛋白表达的影响。该设想如被证实，将是抗心律失常理论上的创新，并为药物研发提供新方向。

Life-threatening arrhythmias resulting from ischemia and infarction is important for risk stratification of patients and for the development of interventions to decrease mortality caused by coronary artery disease. However, antiarrhythmic drugs, with the exception of β-adrenergic receptor blocking drugs and amiodarone，are largely ineffective or even harmful. Arrhythmogenesis in acute myocardial ischemia and chronic infarction are associated with the decrease of resting potential (RP) and inward rectifier potassium current (IK1). However, there are no clinical antiarrhythmic agents mainly acted on resting potential or IK1 up to date. Recently, we reported firstly a selective agonist of IK1, zacopride. By this pharmacological tool, we hypothesized that moderate enhancing IK1, accordingly enhancing or restoring resting potential might exhibit protection against ischemic arrhythmias. Therefore, the antiarrhythmic effect of zacopride would be tested first in acute ischemic and chronic myocardial infarcted(MI) rats subjected to coronary artery ligation. Then in hypoxic atmosphere, the effects of zacopride on IK1 in native rat ventricular myocytes or cloned Kir2.1, Kir2.2 and Kir2.3 channels in HEK 293 cells were to be observed using whole-cell patch-clamp technique.The latter was designed to identify the role of those different Kir2.x channel subunits in this regulation. Finally, the change of mRNA or expression of IK1 / Kir2.x channels in presence and absence of zacopride in acute simulated ischemic /chronic infarcted myocardium were to be compared by Real Time-PCR and Western blot analysis. If the hypothesis is tested to be true, it will bring new ideas to antiarrhythmic theories and shed light on the development of new antiarrhythmic drugs, especially the ones against ischemic arrhythmias.