title: Choline produces antiarrhythmic actions in animal models by cardiac M3 receptors: improvement of intracellular Ca2+ handling as a common mechanism.
abstract: It is well known that choline has protective effects on ischemic arrhythmias. We designed the present study to evaluate the antiarrhythmic effects of choline and to detect its related mechanisms in aconitine-induced rat and ouabain-induced guinea pig models of arrhythmia. Laser scanning confocal microscopy and patch-clamp technique were utilized to study the action of choline on intracellular calcium concentration and L-type calcium current (ICa-L) of cardiac myocytes. M3 receptor antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) was applied preliminarily to evaluate the role of the M3 receptor. Choline significantly increased the survival time of arrhythmic rats and guinea pigs, delayed the onset of arrhythmias and ventricular tachycardia, and decreased the arrhythmia score. The overload of intracellular Ca2+ induced by aconitine or ouabain was reduced in isolated myocytes pretreated with choline. Choline reduced the increased density of ICa-L induced by aconitine or ouabain. Moreover, the beneficial effects of choline were reversed by 4-DAMP. Choline produced antiarrhythmic actions on arrhythmia models by stimulating the cardiac M3 receptor. The mechanism may be related to the improvement of Ca2+ handling.
authors.affiliation: Department of Pharmacology, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang 150081, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Sun
authors.forename: Dan-Lu
authors.initials: DL
authors.lastname: Li
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Du
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
mesh_terms: D000157:Aconitine; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism*; D002794:Choline / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D010042:Ouabain; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000819:agonists* / Q000037:antagonists & inhibitors
chemical_list: D010880:Piperidines; D043587:Receptor, Muscarinic M3; D010042:Ouabain; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002794:Choline; D002118:Calcium; D000157:Aconitine