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Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43
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(1), A(2A) and A(3) receptors, protein kinase C, ATP-dependent potassium (K(ATP)...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928819/ https://www.ncbi.nlm.nih.gov/pubmed/31775376 http://dx.doi.org/10.3390/ijms20235927 |
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author | Diez, Emiliano Raúl Sánchez, Jose Antonio Prado, Natalia Jorgelina Ponce Zumino, Amira Zulma García-Dorado, David Miatello, Roberto Miguel Rodríguez-Sinovas, Antonio |
author_facet | Diez, Emiliano Raúl Sánchez, Jose Antonio Prado, Natalia Jorgelina Ponce Zumino, Amira Zulma García-Dorado, David Miatello, Roberto Miguel Rodríguez-Sinovas, Antonio |
author_sort | Diez, Emiliano Raúl |
collection | PubMed |
description | 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(1), A(2A) and A(3) receptors, protein kinase C, ATP-dependent potassium (K(ATP)) 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(1), A(2A) and A(3) 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(ATP) 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. |
format | Online Article Text |
id | pubmed-6928819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69288192019-12-26 Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43 Diez, Emiliano Raúl Sánchez, Jose Antonio Prado, Natalia Jorgelina Ponce Zumino, Amira Zulma García-Dorado, David Miatello, Roberto Miguel Rodríguez-Sinovas, Antonio Int J Mol Sci Article 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(1), A(2A) and A(3) receptors, protein kinase C, ATP-dependent potassium (K(ATP)) 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(1), A(2A) and A(3) 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(ATP) 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. MDPI 2019-11-25 /pmc/articles/PMC6928819/ /pubmed/31775376 http://dx.doi.org/10.3390/ijms20235927 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Diez, Emiliano Raúl Sánchez, Jose Antonio Prado, Natalia Jorgelina Ponce Zumino, Amira Zulma García-Dorado, David Miatello, Roberto Miguel Rodríguez-Sinovas, Antonio Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43 |
title | Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43 |
title_full | Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43 |
title_fullStr | Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43 |
title_full_unstemmed | Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43 |
title_short | Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of K(ATP) Channels or Connexin 43 |
title_sort | ischemic postconditioning reduces reperfusion arrhythmias by adenosine receptors and protein kinase c activation but is independent of k(atp) channels or connexin 43 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928819/ https://www.ncbi.nlm.nih.gov/pubmed/31775376 http://dx.doi.org/10.3390/ijms20235927 |
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