Abstract： Aim To investigate the relationship between M3-R/IKM3 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/IKM3 may act as a new target for antiarrhythmic agents.