RNA Interference Targeting E637K Mutation of hERG Increases the Rapid Delayed Rectifier Potassium Currents
会议名称：《2011年浙江省心电生理与起搏学术年会》
会议日期：2011年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
摘 要：Congential long-QT syndrome(LQTS) is a collection of monogenic proarrhythmic disorders that predipose affected individuals to sudden death from *** of hERG channel,which encode the rapid delayed rectifier potassium currents(Ikr),are responsible for *** interference(RNAi) is a novel therapeutic strategy in diverse areas of ***,we assess the hypothesis that small interference RNA (siRNAs) could silence the effect of mutation gene of *** has been demonstrated that missense mutation E637K-hERG causes apparent dominant negative suppression of wild-type(WT) hERG channel function.5 siRNAs targeting E637K-hERG were screening and designed by analysis *** results of western blot showed that 2 of them could inhibit the mutant protein expression and did’ t interfere the expression of WThERG *** clamp was performed to test how those 2 siRNAs interfere the gating properties of the E637K-hERG *** data revealed that the Ik of WT/E637K-hERG was restored by siRNA as it was slight different from that of WT-hERG..The maximal current density of the IKr current was increased(49.2%) in cells experssing WT/E637K-hERG with siRNA than that of non- siRNA cells in activation.(294.75±27.44pA/pF in siRNA,149.81±8.82 pA/pF in control,n=5 cells per group,p0.05).The tail current density of IKr current was significantly increased(56.8%) in cells experssing WT /E637K-hERG with siRNA than that in control cells.(732.07±4.21pA/pF in siRNA,315.95±1.22 pA/pF in control,n=5 cells per group,p0.05).In steadyinactivation, the IKr currents of cells experssing WT /E637K-hERG with siRNA was shifted in positive direction. The half-maximal inactivation voltages were -35.41±0.99 mV in siRNA and -51.15±3.16mV in control(n= 6 cells per group,P0.05).Moreover,PD-118057 displayed little effect to WT/E637K-hERG channle in activation and negligible effect in *** conclusion,our data for the first time illustrated the high efficiency and