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Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia-reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent potassium current ( I ), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified. Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch-clamp method. Acetylcholine at 5 μmol/L did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje-ventricle APD dispersion when it was administered after 5 μmol/L pinacidil application. Carbachol at 3 μmol/L reduced the pinacidil-activated K-ATP ), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified. Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch-clamp method. Acetylcholine at 5 μmol/L did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje-ventricle APD dispersion when it was administered after 5 μmol/L pinacidil application. Carbachol at 3 μmol/L reduced the pinacidil-activated I K-ATP under voltage-clamp conditions. Acetylcholine lengthened the ventricular action potential under simulated ischemia condition. In this study, we found that acetylcholine inhibits the I K-ATP and thus suppresses the ventricle-Purkinje APD dispersion. We conclude that parasympathetic tone may reduce the arrhythmogenic substrate exerting a complex antiarrhythmic mechanism during hypoxic conditions.

Increased transmural dispersion of repolarization is an established contributing factor to ventricular tachyarrhythmias. In this study, we evaluated the effect of chronic amiodarone treatment and acute administration of dofetilide in canine cardiac preparations containing electrotonically coupled Purkinje fibers (PFs) and ventricular muscle (VM) and compared the effects to those in uncoupled PF and VM preparations using the conventional microelectrode technique. Dispersion between PFs and VM was inferred from the difference in the respective action potential durations (APDs). In coupled preparations, amiodarone decreased the difference in APDs between PFs and VM, thus decreasing dispersion. In the same preparations, dofetilide increased the dispersion by causing a more pronounced prolongation in PFs. This prolongation was even more emphasized in uncoupled PF preparations, while the effect in VM was the same. In uncoupled preparations, amiodarone elicited no change on the difference in APDs. In conclusion, amiodarone decreased the dispersion between PFs and VM, while dofetilide increased it. The measured difference in APD between cardiac regions may be the affected by electrotonic coupling; thus, studying PFs and VM separately may lead to an over- or underestimation of dispersion.