Melatonin has been reported to cause myocardial electrophysiological changes and prevent ventricular tachycardia or fibrillation (VT/VF) in ischemia and reperfusion. We sought to identify electrophysiological targets responsible for the melatonin antiarrhythmic action and to explore whether melatonin receptor-dependent pathways or its antioxidative properties are essential for these effects. Ischemia was induced in anesthetized rats given a placebo, melatonin, and/or luzindole (MT1/MT2 melatonin receptor blocker), and epicardial mapping with reperfusion VT/VFs assessment was performed. The oxidative stress assessment and Western blotting analysis were performed in the explanted hearts. Transmembrane potentials and ionic currents were recorded in cardiomyocytes with melatonin and/or luzindole application. Melatonin reduced reperfusion VT/VF incidence associated with local activation time in logistic regression analysis. Melatonin prevented ischemia-related conduction slowing and did not change the total connexin43 (Cx43) level or oxidative stress markers, but it increased the content of a phosphorylated Cx43 variant (P-Cx43368). Luzindole abolished the melatonin antiarrhythmic effect, slowed conduction, decreased total Cx43, protein kinase Cε and P-Cx43368 levels, and the IK1 current, and caused resting membrane potential (RMP) depolarization. Neither melatonin nor luzindole modified INa current. Thus, the antiarrhythmic effect of melatonin was mediated by the receptor-dependent enhancement of impulse conduction, which was associated with Cx43 phosphorylation and maintaining the RMP level.

• Keywords
• conduction velocity, connexin-43, melatonin, post-ischemic arrhythmias, potassium current, rat heart, sodium current,
• MeSH
• Anti-Arrhythmia Agents pharmacology   therapeutic use   MeSH
• Myocytes, Cardiac metabolism   MeSH
• Connexin 43 * metabolism   MeSH
• Rats MeSH
• Melatonin * pharmacology   therapeutic use   MeSH
• Receptors, Melatonin metabolism   MeSH
• Arrhythmias, Cardiac drug therapy   prevention & control   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Arrhythmia Agents MeSH
• Connexin 43 * MeSH
• luzindole MeSH Browser
• Melatonin * MeSH
• Receptors, Melatonin MeSH