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Ischemic postconditioning reduces reperfusion arrhythmias by adenosine receptors and protein kinase C activation but is independent of KATP channels or connexin 43
Diez, E.R. (Institute of Medical and Experimental Biology of Cuyo. CONICET)
Sánchez, J.A. (Universitat Autònoma de Barcelona. Departament de Medicina)
Prado, N.J. (Institute of Medical and Experimental Biology of Cuyo. CONICET)
Zumino, A.Z.P. (Institute of Medical and Experimental Biology of Cuyo. CONICET)
García-Dorado, D. (Universitat Autònoma de Barcelona. Departament de Medicina)
Miatello, R.M. (Institute of Medical and Experimental Biology of Cuyo. CONICET)
Rodríguez-Sinovas, A. (Centro de Investigación Biomédica en Red sobre Enfermedades Cardiovasculares (CIBERCV))

Date: 2019
Abstract: Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A, A and A receptors, protein kinase C, ATP-dependent potassium (K) channels, and connexin 43. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which connexin 43 was replaced by connexin 32 and in mice with conditional deletion of connexin 43. Adenosine A, A and A receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a K inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during protein kinase C inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of connexin 43.
Note: Funding: This study was supported by Secretaría de Investigación, Internacionales y Posgrado, Universidad Nacional de Cuyo (06/J505) and by the Spanish, Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III (CIBERCV), cofinanced by the European Regional Development Fund (ERDF-FEDER, a way to build Europe), and by Fundació La Marató de TV3 (n◦. 201536-10). Antonio Rodríguez-Sinovas has a consolidated Miguel Servet contract. Jose A. Sánchez was supported by the International Research Training Group 1566 on Protecting the Heart from Ischemia (PROMISE).
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: Arrhythmia ; Postconditioning ; Adenosine receptors ; PKC ; KATP channels ; Connexin 43
Published in: International journal of molecular sciences, Vol. 20 Núm. 23 (january 2019) , p. 5927, ISSN 1422-0067

DOI: 10.3390/ijms20235927
PMID: 31775376

16 p, 4.3 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2020-01-14, last modified 2020-08-02

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