钩藤碱对{slhumanether--a--go--go}相关基因通道的抑制作用648ActaPhysiologicaSinica,October25,2005,57(5):648-652https://www.sodocs.net/doc/5715403189.htmlResearchPaperReceived2004-09-06Accepted2005-07-27*Correspondingauthor.Tel:+86-27-85736810;Fax:+86-27-85736810;E-mail:ybemail@https://www.sodocs.net/doc/5715403189.htmlInhibitoryeffectofrhynchophyllineonhumanether-a-go-gorelatedgenechannelGUILe1,LIZhi-Wang2,DURong3,YUANGuo-Hui3,LIWei3,RENFa-Xin3,LIJing3,YANGJun-Guo3,*1DepartmentofCardiology,AffiliatedHospital,NantongUniversity,Nantong226000,China;2DepartmentofNeurobiology,HuazhongUniversityofScienceandTechnology,Wuhan430030,China;3InstituteofCardiovascularMedicine,UnionHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan430030,ChinaAbstract:WestudiedtheeffectsofChinesetraditionalmedicinerhynchophylline(Rhy)onhumanether-a-go-gorelatedgene(HERG)channelandcharacterizedtheelectrophysiologicalpropertiesofRhy’spharmacologicaleffectonHERGchannelusingXenopusoocytes.Xenopusoocyteswereinjectedwitheither23nl(5.75ng)HERGcRNAor23nldistilledwater.XenopusoocyteswererandomlyassignedtoreceiveoneofthefollowingdifferentconcentrationsofRhy:(1)control,(2)10μmol/LRhy,(3)101μmol/LRhy,(4)500μmol/LRhy,(5)1000μmol/LRhy,(6)10000μmol/LRhy.Cellcurrentswererecordedinoocytes.ThepeaktailcurrentsofHERGchannelwereinhibitedbyRhy.Theinhibitionwasinadose-dependentmanner[IC50=(773.4±42.5)μmol/L].Experimentwith101μmol/LRhyindicatedthatthedegreeofHERGblockadeshowedsomevoltagedependence(within–40mVto–20mV).KineticanalysesrevealedthatRhydecreasedtherateofchannelactivation.ThefindingsindicatethatRhyinhibitsHERGencodedpotassiumchannels.Itmayunderlinethemolecularmechanismofmyocardialelectrophysiologicalcharacteristicsassociatedwiththisdrug.Keywords:HERG;rhynchophylline;oocyte;two-microelectrodevoltageclamp钩藤碱对humanether-a-go-go相关基因通道的抑制作用桂乐1，李之望2，杜戎3，袁国会3，李伟3，任法鑫3，李婧3，杨钧国3,*1南通大学附属医院心内科，南通226000；2华中科技大学同济医学院神经生物学教研室，武汉430030；3华中科技大学同济医学院协和医院心血管病研究所，武汉430030摘要：将humanether-a-go-go相关基因(HERG)cRNA注射到非洲爪蟾卵母细胞，采用双电极电压钳技术，观察钩藤碱对表达电流的影响。结果显示：(1)钩藤碱抑制HERG通道的表达是浓度依赖性的，IC50为(773.4±42.5)μmol/L。(2)钩藤碱抑制HERG通道的表达是电压依赖性的，最大抑制率在–20mV，为15%。上述结果提示，钩藤碱抑制HERG编码的钾通道，导致心室复极时间延长，揭示了与钩藤碱相关的心肌钾通道的分子生物学基础。关键词：humanether-a-go-go相关基因；钩藤碱；卵母细胞；双电极电压钳中图分类号：R966GoutengisaChinesetraditionalmedicinewhichbelongstotheplantsofRubinaceaegenus.AsaChinesetraditionalmedicine,Goutengwasmainlyusedtotreatailmentsofthecardiovascularandcentralnervousdiseases,suchashypertension,convulsions,numbness,andlighth-eadedness.Rhynchophylline(Rhy)istheprimarypharma-cologicalcomponentofGouteng[1].ThepharmacologicalactionsofRhyoncardiovascularsystemwereextensivelystudied.IthasbeenshownthatRhyhasprotectiveeffectoncardiacarrhythmias.Rhycandelaytheatrio-ventricu-larandtheintraventricularconduction.TheintervalofP-R,P-P,Q-T,andQRSwavesareprolongedmarkedly[2,3].SomestudiesindicatedthattheelectrophysiologicaleffectsofRhyresultfromtheblockadeofK+channelandL-type本文来源：网络收集与整理，如有侵权，请联系作者删除，谢谢！