简介：ObjectivesToinvestigatetheanti-apoptoticeffectsofmesenchymalstemcells(MSCs)onhypoxicinjuredcardiacmyocytesinvitro.MethodsMSCswereisolatedfrombonemarrowofSprague-Dawley(SD)rats,andcardiacmyocytesfromneonatalrats.Theratcardiacmyocyteswereco-culturedwithMSCsorMSC-conditionedmediainanoxia(95%N2+5%CO2)for72hours.CellapoptosiswasmeasuredbyHoechst33258staining.TheexpressionofBcl-2andBaxincardiacmyocyteswastestedbyWesternBlot.ResultsTheapoptoticratewas51.6%±2.4%whencardiacmyocyteswereculturedincontinuoushypoxiaandwassignificantlydecreasedwhencardiacmyocyteswerecoculturedwithMSCsorMSC-conditionedmedia(15.1%±5.4%and24.0%±4.2%respectively,P<0.001).ThedecreasedexpressionofBaxinthecardiacmyocyteswasgreatlyrelatedtothedecreasingofapoptosis,buttherewasnodifferenceinBcl-2expressionamongthesegroups.ConclusionsCo-culturedMSCsshowedsignificantanti-apoptoticeffectsoncardiacmyocytesincontinuoushypoxia.ThemechanismmaybetheinteractofcelltocellandparacrineofcytokineswhicheffectedtheexpressionofBaxinthecardiacmyocytes.

简介：ObjectivesRecentstudieshavedescribedregionaldifferencesintheelectrophysiologyandpharmacologyofventricularmyocardiumincanine,feline,rat,guineapig,andhumanhearts.ThishasbeenshowntobeduetoasmallerIKsandalagersodium-calciumexchangecurrent(INa-Ca)andlateINainMregion(deepsubepicardialtomidmyocardial).Studiesfromourlaboratoryhavefoundanewrepolarizationcurrent-nonselectivecationcurrent(NSCCs)existinginrabbitrightventricularmyocytes.MethodsWeexaminedthecharacteristicsofNSCCsinepicardial,Mregion,andendocardialcellsisolatedfromtherabbitleftventriclewithstandardmicroelectrodeandwhole-cellpatch-clamptechniques.ThepermeabilitytoNa+,K+,Li+,Cs+butnottoCl-indicatingthatitwasanonselectivecationcurrent.Gd3+(0.1mmol/l)andLa3+(0.1mmol/l)canblockthecurrentmarkedly.ResultsFurthercharacterizationofNSCCswassignificantlysmallerinMcellsthaninepicardialandendocardialcells.NSCCscurrentdensitywassignificantlysmallerinMcellsthaninepicardialandendocardialcells.Withrepolarizationto-80mV,INscurrentdensitywas(-0.44±0.05)PA/PFinendocardialcells,(-0.12±0.05)PA/PFinMcellsand(-0.28±0.07)PA/PFinepicardialcells;andwithrepolarizationto+30mV,INscurrentdensitywas(1.09±0.29)PA/PFinendocardialcells,(0.38±0.09)PA/PFinMcellsand(0.91±0.32)PA/PFinepicardialcells.ConclusionsTransmuraldispersionofrepolarizationwasduetotheheterogeneityofNSCCsinrabbitleftventricleepicardial,endocardialmyocytesandMcells.Thesefindingsmayadvanceourunderstandingoftheionicbasisforourunderstandingoffactorscontributingtothedevelopmentofcardiacarrhythmias.

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：ObjectivesTheeffectsofcarvediloloncalciumcurrent(ICa)wereinvestigatedinisolatedadultratventricularmyocytes.MethodsICawasrecordedbyusingwhole-cellpatch-clamprecordingtechnique.ResultsCarvedilolreversiblyinhibitedICainaconcentration-dependentmanner,carvedilolat0.1,0.3,1and10μmol/LintheextracellularsolutiondecreasedpeakICaby1.52%,18.04%,37.34%and72.18%,respectively.Thesteady-stateinactivationcurveofICawasshiftedtomorenegativepotentials,whiletheactivationcurvewasnotaltered.Therecoveryfrominactivationwasshiftedtorightdirection,itcouldnotberecoveredcompletely.Inaddition,Pretreatmentofventricularmyocyteswithprazosinandpropranololcouldn'tblockthecarvedilol-inducedreductionofICa.ConclusionsCarvedilolinhibitsICainadultratventricularmyocytesbymechanismsinvolvingpreferentialinteractionwiththeinactivatedstateofcalciumchannel.

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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简介：ObjectivesToinvestigateeffectofAngll,captoprilonsingleguineamyocytesonL-typecalciumcurrentandsodiumcurrent.MethodsMembranepatchclampwholecellrecordingtechniquewasusedtoinvestigateeffectofangll,captoprilonL-Camaximumcurrentdensityandsodiummaximumcurrentdensity.ResutlsAngllincreasedthemaximumcurrentdensitycomparedwithcontrolafterperfused5min,357.7±219.7Vs279.5±240.5PA/PF,increaserateis27.9%,theshapeofcurrent-voltagerelationshipcurvewasunchanged,peakedat+10mv,indicatedthatangllincreasedL-Cacurrentdensityinvoltage-dependent.Afterperfusedwithcaptopril,captopril+angll3,5min,L-Cacurrentwasrecorded,resultssuggestL-Camaximumcurrentdensitydecreasedsignificantlycomparedwithcontrol,incaptoprilgroup,128.4±92.6Vs286.2±89.7,66.7±68.3Vs286.2±89.7,respectively,rateofinhibitionis55.1%,76.6%,respectively.L-Cacurrentfurtherdecreasedincaptoprilpe

简介：ThepresentstudywasdesignedtodeterminetheeffectsofGuanfubaseA(GFA)onthelatesodiumcurrent(INa.L),transientsodiumcurrent(INa.T),HERGcurrent(IHERG),andKv1.5current(IKv1.5).ThevaluesofINa.L,INa.T,IHERGandIKv1.5wererecordedusingthewhole-cellpatchclamptechnique.Comparedwithotherchannels,GFAshowedselectiveblockingactivityinlatesodiumchannel.ItinhibitedINa.Linaconcentration-dependentmannerwithanIC50of(1.57±0.14)μmol·L-1,whichwassignificantlylowerthanitsIC50valuesof(21.17±4.51)μmol·L-1fortheINa.T.TheinhibitoryeffectofGFAonINa,Lwasnotaffectedby200μmol·L-1H2O2.ItinhibitedIHERGwithanIC50of(273±34)μmol·L-1andhasslightblockingeffectonIKv1.5,decreasingIKv1.5byonly20.6%at200μmol·L-1.Insummary,GFAinhibitedINa.Lselectivelyandremainedsimilarinhibitioninpresenceofreactiveoxygenspecies..ThesefindingsmaysuggestanovelmolecularmechanismforthepotentialclinicalapplicationofGFAinthetreatmentofcardiovasculardisorders.