缺血对心肌中连结蛋白43和乙酰胆碱M受体亚型M3 (M3-mAChR)结合的影响.ppt

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1、Ischemia Impairs the Association Between Connexin 43 and M3 Subtype of Acetylcholine Muscarinic Receptor (M3-mAChR) in Ventricle Myocytes,De-Li Dong Department of Pharmacology, Harbin Medical University, Harbin, P.R.China,Introduction,Multiple subtypes of muscarinic acetylcholine receptors expressed

2、 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 antiarrhythmogeni

3、c effects accompanied by prevention of the loss of Cx43 during acute MI.(Circulation. 2005 ;112(2):164-70.),The association between Connexin43 and M3-mAChR in ventricular myocytes. The role of M3-mAChR in cytoprotection of myocardial infarction.,Introduction,Results 1.Expression of M3-R and Connexin

4、 43 in the heart.,A confocal image showing the expression of connexin 43 in myocardium under control conditions and after ischemia.,A confocal image showing the expression of connexin 43 (red) and M3-mAChR in a isolated myocyte.,2. Connexin 43 is coimmunoprecipitated with M2/M3-R,3. The effects of i

5、schemia on the expression of M-R and connexin 43.,The effect of ischemia on the expression of connexin 43 in the plasma membrane.,The effect of ischemia on the association between M2 or M3-mAChR and connexin 43.,4. The effect of choline pretreatment on the association between M3/M2 mAChR and connexi

6、n 43.,5. Effects of Choline on Hemodynamic Parameters during Coronary Artery Occlusion.,6. Effects of choline on ischemic arrhythmias and the potential role of M3-mAChRs.,7. Effect of choline on infarct size and the potential role of M3-mAChRs.,8. Effect of choline on cardiomyocytes apoptosis and the potential role of M3-mAChRs.,Conclusions,Connexin 43 interacts with M2/M3-mAChR Ischemia specifically impairs the association between M3-mAChR and connexin 43. Choline improves cardiac function and reduces ischemic myocardial injuries via stimulating the cardiac M3-mAChRs.,Thanks,

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