缺血对心肌中连结蛋白和乙酰胆碱M受体亚型MMmAChR结合的影响

缺血对心肌中连结蛋白和乙酰胆碱M受体亚型MMmAChR结合的影响第1页/共18页IntroductionMultiplesubtypesofmuscarinicacetylcholinereceptorsexpressedinmyocardium,includingM1,M2,M3,M5-R.

(MolPharmacol.2001;59:1029-36.)

TheM3Receptor-mediatedK+Current(IKM3),aGqProtein-coupledK+Channel.

(JBiolChem.2004,279,21774-8)Connexin43(Cx43)-gapjunctionchannels.(Cell1996;84(3):381-8.)VagalnervestimulationexertsantiarrhythmogeniceffectsaccompaniedbypreventionofthelossofCx43duringacuteMI.(Circulation.2005;112(2):164-70.)第2页/共18页TheassociationbetweenConnexin43andM3-mAChRinventricularmyocytes.TheroleofM3-mAChRincytoprotectionofmyocardialinfarction.Introduction第3页/共18页Results

1.ExpressionofM3-RandConnexin43intheheart.第4页/共18页Aconfocalimageshowingtheexpressionofconnexin43inmyocardiumundercontrolconditionsandafterischemia.第5页/共18页Aconfocalimageshowingtheexpressionofconnexin43(red)andM3-mAChRinaisolatedmyocyte.第6页/共18页2.Connexin43iscoimmunoprecipitatedwithM2/M3-R第7页/共18页3.TheeffectsofischemiaontheexpressionofM-Randconnexin43.

第8页/共18页Theeffectofischemiaontheexpressionofconnexin43intheplasmamembrane.

第9页/共18页TheeffectofischemiaontheassociationbetweenM2orM3-mAChRandconnexin43.

第10页/共18页4.TheeffectofcholinepretreatmentontheassociationbetweenM3/M2mAChRandconnexin43.第11页/共18页5.EffectsofCholineonHemodynamicParametersduringCoronaryArteryOcclusion.第12页/共18页6.EffectsofcholineonischemicarrhythmiasandthepotentialroleofM3-mAChRs.

第13页/共18页7.EffectofcholineoninfarctsizeandthepotentialroleofM3-mAChRs.

第14页/共18页8.EffectofcholineoncardiomyocytesapoptosisandthepotentialroleofM3-mAChRs.

第15页/共18页ConclusionsConnexin43interactswithM2/M3-mAChRIschemiaspecificallyimpairstheassociationbetweenM3-mAChRandconnexin43.Cholineimprovescardiacfunctionandreducesischemicmyocardial