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.pptxVIP

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 IntroductionMultiple subtypes of muscarinic acetylcholine receptors expressed in myocardium, including M1,M2,M3,M5-R. (Mol Pharmacol. 2001 ;59:1029-36.) The M3 Receptor-mediated K+ Current (IKM3), a Gq Protein-coupled K+ Channel. (J Biol Chem.2004, 279, 21774-8) Connexin 43(Cx43)-gap junction channels. (Cell 1996;84(3):381-8.)Vagal nerve stimulation exerts antiarrhythmogenic effects accompanied by prevention of the loss of Cx43 during acute MI.(Circulation. 2005 ;112(2):164-70.)第2页/共18页 The association between Connexin43 and M3-mAChR in ventricular myocytes.The role of M3-mAChR in cytoprotection of myocardial infarction.Introduction第3页/共18页 Results1.Expression of M3-R and Connexin 43 in the heart.第4页/共18页 A confocal image showing the expression of connexin 43 in myocardium under control conditions and after ischemia.第5页/共18页 A confocal image showing the expression of connexin 43 (red) and M3-mAChR in a isolated myocyte.第6页/共18页 2. Connexin 43 is coimmunoprecipitated with M2/M3-R第7页/共18页 3. The effects of ischemia on the expression of M-R and connexin 43. 第8页/共18页 The effect of ischemia on the expression of connexin 43 in the plasma membrane. 第9页/共18页 The effect of ischemia on the association between M2 or M3-mAChR and connexin 43. 第10页/共18页 4. The effect of choline pretreatment on the association between M3/M2 mAChR and connexin 43. 第11页/共18页 5. Effects of Choline on Hemodynamic Parameters during Coronary Artery Occlusion.第12页/共18页 6. Effects of choline on ischemic arrhythmias and the potential role of M3-mAChRs. 第13页/共18页 7. Effect of choline on infarct size and the potential role of M3-mAChRs. 第14页/共18页 8. Effect of choline on cardiomyocytes apoptosis and the potential role of M3-mAChRs. 第15页/共18页 ConclusionsConnexin 43 interacts with M2/M3-mAChRIschemia specifically impairs the association between M3-mAChR and connexin 43.Choline improves cardiac function and reduces ischemic myocardial injurie