化合物QO-58对KCNQ1/KCNE1/IKs通道电流调节作用的研究  

The Effect of QO-58 on KCNQ1/KCNE1/IKs Potassium Channel Currents

作　　者：张凡[1] 李晗[2] 丁杰[1] 李毅[1] 张海林[1] 

机构地区：[1]河北医科大学药理学教研室,石家庄050017 [2]河北医科大学第三医院关节科,石家庄050017

出　　处：《中国细胞生物学学报》2015年第4期508-513,共6页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:31401199);河北省自然科学基金(批准号:H2015206427);河北省教育厅优秀青年基金(批准号:YQ2014030);第56批中国博士后科学基金(批准号:2014M560194)资助的课题~~

摘　　要：慢激活延迟整流钾电流(slowly activated delayed rectifier potassium current,IKs)由KCNQ1通道与KCNE1通道共同编码。KCNQl或KCNEl通道电流功能上调能够引发短QT综合征。全新化学结构化合物QO-58对KCNQ1-5通道具有开放作用。该文采用电生理膜片钳技术探讨QO-58对KCNQl/KCNEl/IKs通道电流作用,观察QO-58的心脏电生理毒性。结果表明,化合物QO-58能够浓度依赖性地增大KCNQ1/KCNE1通道电流,并且引起KCNQ1/KCNE1通道电流电压关系曲线向超极化方向移动。QO-58能够轻微增大豚鼠心室肌IKs通道电流,但对豚鼠乳头肌动作电位时程无显著影响。结果提示,QO-58心脏电生理毒性较低,具有进一步研发成为治疗兴奋性增强等相关疾病的新型药物的潜力。Slowly activated delayed rectifier potassium current（IKs） is formed by KCNQ1 and KCNE1 channel. Up regulation of KCNQ1 or KCNE1 channel currents leads to short QT syndrome. Novel compound QO-58 activates KCNQ1-5 channel. Patch clamp technique was used to study the effect of QO-58 on KCNQl/KCNEl/IKs channel currents to test the toxicity of cardiac electrophysiology. The results showed that compound QO-58 concentration-dependently activated KCNQl/KCNEl currents and shifted the KCNQl/KCNEl channel activation curve to hyperpolarization direction. QO-58 slightly enhanced IKs currents expressed in guinea pig myocytes, but had no effect on action potential duration of guinea pig papillary muscle. This suggested that the cardio toxicity of QO-58 was low. And compound QO-58 had the potential to be developed further to treat disease related with neuronal hyperexcitability.

关 键 词：KCNQ1通道 KCNE1通道 IKS QO-58 膜片钳 

分 类 号：R96[医药卫生—药理学]