M3-R/IK(M3)--a new target of antiarrhythmic agents.
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.
Liu
Yan
Y
Department of Pharmacology, Bio-pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory, Harbin Medical University, Harbin 150086, China.
Xu
Chao-qian
CQ
Jiao
Jun-dong
JD
Wang
Hui-zhen
HZ
Dong
De-li
DL
Yang
Bao-feng
BF
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
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D043587:Receptor, Muscarinic M3; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002794:Choline