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《Acta Pharmaceutica Sinica》 2005-01
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M_3-R/IK_(M_3)a new target of antiarrhythmic agents

LIU Yan, XU Chao-qian, JIAO Jun-dong, WANG Hui-zhen, DONG De-li, YANG Bao-feng* (Department 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 M_3-R/IK_M_3 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 M_3 receptor on the occurrence of arrhythmias and its possible mechanisms were studied. Results In acute ischemic model of rats, the M_3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine-methiodide (4DAMP) increased the occurrence of arrhythmias, and the M_3 receptor agonist choline suppressed the onset and the development of arrhythmias (P0.01). No change was observed after treatment with other receptor antagonists (M_1, M_2, and M_4). With patch-clamp techniques, it was found that choline induced K+ current could be inhibited by 4DAMP. Antagonists toward M_1, M_2,_ and M_4 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 M_3 receptor. M_3-R/IK_M_3 may act as a new target for antiarrhythmic agents.
【Fund】: NationalNaturalScienceFoundationofChina (30271599 2004CCA06700).
【CateGory Index】: R96
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