Abstract: AimTo investigate the relationship between M₃-R/IKM₃ and arrhythmia in order to find a new target for antiarrhythmic agents. MethodsUsing 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. ResultsIn 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. ConclusionCholine 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.