心房纤颤是临床最常见的心律失常，而现有治疗药物极易引起更为严重的室性心律失常。IKur（Kv1.5）钾离子通道仅在人心房表达，以IKur通道为作用靶点寻找选择性和特异性阻滞剂治疗房颤已成为国际前沿热点，但目前尚无特异、高效的IKur阻滞剂问世。本课题利用转基因表达和以PCR为基础的碱基定点变异等技术方法，将构成人心脏IKur通道的hKv1.5 基因及其变异转基因表达到CHO细胞，再采用膜片钳技术，研究化合物LY294002及其结构衍生物对hKv1.5通道及变异通道的影响，寻找理想的选择性Kv1.5通道阻断剂，延长心房动作电位有效不应期、消除折返激动治疗房颤的同时，对心脏其它离子通道（如心室IKs和IKr钾通道）无影响，以期发现不引起室性心律失常的新型房颤治疗药物。本研究直接从分子水平上观察化合物与靶离子通道的作用，可为房颤这一顽疾的创新治疗药物研发提供全新化合物。

The atrial fibrillation (AF) is the most common arrhythmia in clinic. However, the the currently available drugs for the treatment of AF are highly liable to cause more serious ventricular arrhythmias. IKur (Kv1.5) potassium channel has been confirmed to be expressed only in human atrium. Therefore, IKur as a target for the selective and specific blocker used for the treatment of AF now has been one of the most frontier hotspots in the world. But no such a blocker with the specificity and high efficiency has been introduced up to now. In the present study, the methods such as heterologous transgene expression and PCR-based site-directed mutagensis are used to transfect human Kv1.5 gene (encoding IKur channel) and its mutants into CHO cells. And then patch-clamp technique is employed to study the effects of compound LY294002 and its derivatives on both hKv1.5 and its mutant channels. The aim of present study is to seek ideal Kv1.5 channel blockers that could prolong the atrial action potential duration (APD) and effective refractory period (ERP) to abolish reentry so as to be developed as new drugs for the AF treatment. It is expected that,while being used to treat AF, the new drugs do not affect other cardiac ion channel (eg.ventricular IKs and IKr) to induce ventricular arrhythmias. The present study can directly examine the functional correlation between chemical compounds and target ion channel, resultantly providing new chemical componuds for the new drug development to treat the refractory disease AF.