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M3-R/IK(M3)--a new target of antiarrhythmic agents
Yan Liu1, Chao-qian Xu, Jun-dong Jiao
1Department of Pharmacology, Bio-pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory, Harbin Medical University, Harbin 150086, China.
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.
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