tailieunhanh - Báo cáo khoa học: Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium

Our recent studies have shown that, as indicated by vagal stimulation, an acetylcholinesterase inhibitor donepezil, an anti-Alzheimer’s disease drug, prevents progression of heart failure in rats with myocardial infarction, and activates a common cell survival signal shared by acetylcholine (ACh) in vitro. | Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium Yoshihiko Kakinuma1 Tsuyoshi Akiyama2 and Takayuki Sato1 1 Department of Cardiovascular Control Kochi Medical School Nankoku Japan 2 Department of Cardiac Physiology NationalCardiovascular Center Research Institute Suita Japan Keywords acetylcholine cardiomyocytes donepezil energy metabolism non-neuronal cholinergic system Correspondence Y. Kakinuma Department of Cardiovascular Control Kochi Medical School Nankoku Kochi 783-8505 Japan Fax 81 88 880 2310 Tel 81 88 880 2587 E-mail kakinuma@ Received 13 May 2009 revised 8 July 2009 accepted 10 July 2009 doi Our recent studies have shown that as indicated by vagal stimulation an acetylcholinesterase inhibitor donepezil an anti-Alzheimer s disease drug prevents progression of heart failure in rats with myocardial infarction and activates a common cell survival signal shared by acetylcholine ACh in vitro. On the basis of this and evidence that vagal innervation is extremely poor in the left ventricle we assessed the hypothesis that ACh is produced by cardiomyocytes which promotes its synthesis via a positive feedback mechanism. Rat cardiomyocytes expressed choline acetyltransferase ChAT in the cytoplasm and vesicular acetylcholine transporter with the vesicular structure identified by immunogold electron microscopy suggesting that cardiomyocytes possess components for ACh synthesis. Intracellular ACh in rat cardiomyocytes was identified with physostigmine or donepezil. However with atropine the basal ACh content was reduced. In response to exogenous ACh or pilocarpine cardiomyocytes increased the transcriptional activity of the ChAT gene through a muscarinic receptor and ChAT protein expression and finally the intracellular ACh level was upregulated by pilocarpine. Knockdown of ChAT by small interfering RNA .