M3-R/IK(M3)--a new target of antiarrhythmic agents

Yao Xue Xue Bao. 2005 Jan;40(1):8-12.

Abstract

Aim: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents*
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / physiopathology*
  • Cell Separation
  • Choline / pharmacology
  • Guinea Pigs
  • Heart Ventricles
  • Male
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology
  • Piperidines
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M3* / agonists
  • Receptor, Muscarinic M3* / antagonists & inhibitors

Substances

  • Anti-Arrhythmia Agents
  • Piperidines
  • Receptor, Muscarinic M3
  • 4-diphenylacetoxy-1,1-dimethylpiperidinium
  • Choline