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

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 The association between Connexin43 and M3-mAChR in ventricular myocytes. The role of M3-mAChR in cytoprotection of myocardial infarction. Results1.Expression of M3-R and Connexin 43 in the heart. 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. * * Multiple 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.) Introduction 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 ischemia 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 connexin 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 s