title: M3-R/IK(M3)--a new target of antiarrhythmic agents.
abstract: OBJECTIVE
  To investigate the relationship between M3-R/IK(M3) and arrhythmia in order to find a new target for antiarrhythmic agents.
  
  
  METHODS
  Using the acute ischemic model of rats and patch-clamp techniques, the effects of the M3 receptor on the occurrence of arrhythmias and its possible mechanisms were studied.
  
  
  RESULTS
  In acute ischemic model of rats, the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine-methiodide (4DAMP) increased the occurrence of arrhythmias, and the M3 receptor agonist choline suppressed the onset and the development of arrhythmias (P < 0. 01). No change was observed after treatment with other receptor antagonists (M1, M2, and M4). With patch-clamp techniques, it was found that choline induced K+ current could be inhibited by 4DAMP. Antagonists toward M1, M2, and M4 receptors all failed to alter the current.
  
  
  CONCLUSIONS
  Choline modulates the cellular electrical properties of the heart, probably by activating a K+ current via stimulation of the M3 receptor. M3-R/IK(M3) may act as a new target for antiarrhythmic agents.
authors.affiliation: Department of Pharmacology, Bio-pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory, Harbin Medical University, Harbin 150086, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Chao-qian
authors.initials: CQ
authors.lastname: Xu
authors.forename: Jun-dong
authors.initials: JD
authors.lastname: Jiao
authors.forename: Hui-zhen
authors.initials: HZ
authors.lastname: Wang
authors.forename: De-li
authors.initials: DL
authors.lastname: Dong
authors.forename: Bao-feng
authors.initials: BF
authors.lastname: Yang
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D002469:Cell Separation; D002794:Choline / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D010880:Piperidines; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000819:agonists / Q000037:antagonists & inhibitors
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D043587:Receptor, Muscarinic M3; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002794:Choline