A Role for BK Channels in Heart Rate Regulation in Rodents 英文参考文献.docVIP

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A Role for BK Channels in Heart Rate Regulation in Rodents 英文参考文献.doc

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A Role for BK Channels in Heart Rate Regulation in Rodents 英文参考文献

ARoleforBKChannelsinHeartRateRegulationin Rodents WendyL.Imlach1,5¤,SarahC.Finch2,JohnH.Miller3,AndreaL.Meredith4,JulieE.Dalziel1* 1AgResearch, Grasslands Research Centre, Palmerston North, New Zealand, 2AgResearch, Ruakura Research Centre, Hamilton, New Zealand, 3School of Biological Sciences,VictoriaUniversityofWellington,Wellington,NewZealand,4DepartmentofPhysiology,UniversityofMarylandSchoolofMedicine,Baltimore,Maryland,United StatesofAmerica,5DepartmentofPharmacologyandToxicology,UniversityofOtago,Dunedin,NewZealand Abstract TheheartgeneratesandpropagatesactionpotentialsthroughsynchronizedactivationofionchannelsallowinginwardNa+ 2+ + + andCa andoutwardK currents.ThereareanumberofK channeltypesexpressedintheheartthatplaykeyrolesin regulating the cardiac cycle. Large conductance calcium-activated potassium (BK) ion channels are not thought to be directlyinvolvedinheartfunction.Herewepresentevidencethatheartratecanbesignificantlyreducedbyinhibitingthe activityofBKchannels.AgentsthatspecificallyinhibitBKchannelactivity,includingpaxillineandlolitremB,slowedheart rateinconsciouswild-typemiceby30%and42%,respectively.HeartrateofBKchannelknock-outmice(Kcnma12/2 )was notaffectedbytheseBKchannelinhibitors,suggestingthatthechangestoheartratewerespecificallymediatedthrough BKchannels.ThepossibilitythattheseeffectsweremediatedthroughBKchannelsperipheraltotheheartwasruledout withexperimentsusingisolated,perfusedrathearts,whichshowedasignificantreductioninheartratewhentreatedwith theBKchannelinhibitorspaxilline(1mM),lolitremB(1mM),andiberiotoxin(0.23mM),of34%,60%,and42%,respectively. Furthermore,paxillinewasshowntodecreaseheartrateinadose-dependentmanner.TheseresultsimplicateBKchannels locatedinthehearttobedirectlyinvolvedintheregulationofheartrate. Citation: Imlach WL, Finch SC, Miller JH, Meredith AL, Dalziel JE (2010) A Role for BK Channels in Heart Rate Regulation in Rodents. PLoS ONE 5(1): e8698. doi:10.1371/journal.pone.0008698 Editor:ArnoldSchwartz,UniversityofCin