简介：BackgroundAtrialfibrillation(AF)isthemostcommonsustainedcardiacarrhythmiawithouteffectivetreatment.AFisassociatedwithatrialconductiondisturbancescausedbyelectricaland/orstructuralremodel-ing.Buttheroleofconnexin(Cx)43intheregulationofLtypecalciumchannel(LCC)remainsunclear.WehypothesizedthatCx43mightco-localizeandregulatetheLtypecalciumchannelcurrent(ICa,L).MethodsReal-timePCRandwhole-cellpatchclampwereusedtodetecttheexpressionofLCC1csubunitandthecurrentdensityofICa,L,beforeandafterCx43knockingdownrespectively.Theco-localizationofCx43withLCCwasinvestigatedbyco-immunoprecipitationandconfocalmicroscopy.ResultsKnockingdownofCx43significantlyinhibitedthecurrentdensityofICa,LthroughdecreasingthegeneexpressionofLCCα1cinculturedatrium-derivedmyocytes(HL-1cells).Cx43co-localizedwithLCCα1csubunitinatrialmyocytes.ConclusionsCx43regulatestheICa,LinatrialmyoctyesthroughLCC,representingapotentialpathogenicmechanisminatrialarrhythmias.

简介：Toinvestigatetheeffectsofsimvastatinonmembraneioniccurrentsinleftventricularmyocytesofrabbitheartsufferingfromacutemyocardialinfarction(AMI),soastoexploretheionicmechanismofstatintreatmentforantiarrhythmia.MethodsForty-fiveNewZealandrabbitswererandomlydividedintothreegroups:AMIgroup,simvastatininterventiongroup(Statingroup)andsham-operatedcontrolgroup(CON).Rabbitswereinfarctedbyligationoftheleftanteriordescendingcoronaryarteryafteradministrationoforalsimvastatin5mg·kg-1·d-1(Statingroup)orplacebo(AMIgroup)for3days.Singleventricularmyocyteswereisolatedenzymaticallyfromtheepicardialzoneoftheinfractedregion72hlater.Wholecellpatchclamptechniquewasusedtorecordmembraneioniccurrents,includingsodiumcurrent(INa),L-typecalciumcurrent(ICa-L)andtransientoutwardpotassiumcurrent(Ito).Results①Therewasnotsignificantdifferenceinserumcholesterolconcentrationamongthreegroups.②ThepeakINacurrentdensity(at-30mV)wassignificantlydecreasedinAMIgroup(-25.26±5.28,n=13),comparingwithCON(-42.78±5.48,n=16),P<0.05,whileitwassignificantlyincreasedinStatingroup(-39.83±5.65pA/pF,n=12)comparingwithAMIgroup,P<0.01;ThepeakICa-Lcurrentdensity(at0mV)wassignificantlydecreasedinAMIgroup(-3.43±0.92pA/pF,n=13)comparingwithCON(-4.56±1.01pA/pF,n=15),P<0.05,whileitwassignificantlyincreasedinStatingroup(-4.18±0.96pA/pF,n=12)comparingwithAMIgroup,P<0.05;TheItocurrentdensity(at+60mV)wassignificantlydecreasedinAMIgroup(11.41±1.94pA/pF,n=13)comparingwithCON(17.41±3.13pA/pF,n=15),P<0.01,whileitwassignificantlyincreasedinStatingroup(16.11±2.43pA/pF,n=14)comparingwithAMIgroup,P<0.01.ConclusionsAMIinducessignificantdown-regulationofINa,ICa-LandIto.Pretreatmentwithsimvastatincouldattenuatethischangewithoutloweringtheserumcholesterollevel,suggestingthatsimvastatincouldrev

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