Melatonin receptor activation protects against low potassium-induced ventricular fibrillation by preserving action potentials and connexin-43 topology in isolated rat hearts.

Autor: Prado NJ; Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas, Mendoza, Argentina., Egan Beňová T; Center of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart Research, Bratislava, Slovakia., Diez ER; Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas, Mendoza, Argentina.; Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina., Knezl V; Center of Experimental Medicine, Slovak Academy of Sciences, Institute of Experimental Pharmacology and Toxicology, Bratislava, Slovakia., Lipták B; Center of Experimental Medicine, Slovak Academy of Sciences, Institute of Experimental Pharmacology and Toxicology, Bratislava, Slovakia., Ponce Zumino AZ; Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas, Mendoza, Argentina.; Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina., Llamedo-Soria M; Department of Electronic Engineering, Universidad Tecnológica Nacional, Buenos Aires, Argentina., Szeiffová Bačová B; Center of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart Research, Bratislava, Slovakia., Miatello RM; Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas, Mendoza, Argentina.; Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina., Tribulová N; Center of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart Research, Bratislava, Slovakia.
Jazyk: angličtina
Zdroj: Journal of pineal research [J Pineal Res] 2019 Nov; Vol. 67 (4), pp. e12605. Date of Electronic Publication: 2019 Sep 10.
DOI: 10.1111/jpi.12605
Abstrakt: Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium-induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin-43 preservation. After stabilization in Krebs-Henseleit solution (4.5 mEq/L K + ), isolated hearts from Wistar rats underwent perfusion with low-potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation. Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin-43 were examined. Melatonin reduced the incidence of low potassium-induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin-43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin-43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium-induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin-43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent.
(© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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