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In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice
Cardiac cells depend on specific sarcolemmal ion transporters to assure the correct intracellular pH regulation. The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms. In the heart two different NBC isoforms have been described: the electroneutral NBCn1 (1Na(+):1 [Fo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082548/ https://www.ncbi.nlm.nih.gov/pubmed/35548416 http://dx.doi.org/10.3389/fcvm.2022.862118 |
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author | Di Mattía, Romina A. Díaz Zegarra, Leandro A. Valverde, Carlos A. Blanco, Paula G. Jaquenod De Giusti, Carolina Portiansky, Enrique L. Aiello, Ernesto A. Orlowski, Alejandro |
author_facet | Di Mattía, Romina A. Díaz Zegarra, Leandro A. Valverde, Carlos A. Blanco, Paula G. Jaquenod De Giusti, Carolina Portiansky, Enrique L. Aiello, Ernesto A. Orlowski, Alejandro |
author_sort | Di Mattía, Romina A. |
collection | PubMed |
description | Cardiac cells depend on specific sarcolemmal ion transporters to assure the correct intracellular pH regulation. The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms. In the heart two different NBC isoforms have been described: the electroneutral NBCn1 (1Na(+):1 [Formula: see text]) and the electrogenic NBCe1 (1Na(+):2 [Formula: see text]). NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). In addition to regulating the pH, the NBC is a source of sodium influx. It has been postulated that NBC could play a role in the development of hypertrophy. The aim of this research was to study the contribution of NBCe1 in heart electrophysiology and in the development of heart hypertrophy in an in vivo mouse model with overexpression of NBCe1. Heart NBCe1 overexpression was achieved by a recombinant cardiotropic adeno-associated virus (AAV9) and was evidenced by western-blot and qPCR. AAV9-mCherry was used as a transduction control. NBCe1 overexpression fails to increase heart growth. Patch clamp and electrocardiogram were performed. We observed a reduction on both, ventricular myocytes APD and electrocardiogram QT interval corrected by cardiac rate, emphasizing for the first time NBCe1 relevance for the electrical activity of the heart. |
format | Online Article Text |
id | pubmed-9082548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90825482022-05-10 In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice Di Mattía, Romina A. Díaz Zegarra, Leandro A. Valverde, Carlos A. Blanco, Paula G. Jaquenod De Giusti, Carolina Portiansky, Enrique L. Aiello, Ernesto A. Orlowski, Alejandro Front Cardiovasc Med Cardiovascular Medicine Cardiac cells depend on specific sarcolemmal ion transporters to assure the correct intracellular pH regulation. The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms. In the heart two different NBC isoforms have been described: the electroneutral NBCn1 (1Na(+):1 [Formula: see text]) and the electrogenic NBCe1 (1Na(+):2 [Formula: see text]). NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). In addition to regulating the pH, the NBC is a source of sodium influx. It has been postulated that NBC could play a role in the development of hypertrophy. The aim of this research was to study the contribution of NBCe1 in heart electrophysiology and in the development of heart hypertrophy in an in vivo mouse model with overexpression of NBCe1. Heart NBCe1 overexpression was achieved by a recombinant cardiotropic adeno-associated virus (AAV9) and was evidenced by western-blot and qPCR. AAV9-mCherry was used as a transduction control. NBCe1 overexpression fails to increase heart growth. Patch clamp and electrocardiogram were performed. We observed a reduction on both, ventricular myocytes APD and electrocardiogram QT interval corrected by cardiac rate, emphasizing for the first time NBCe1 relevance for the electrical activity of the heart. Frontiers Media S.A. 2022-04-25 /pmc/articles/PMC9082548/ /pubmed/35548416 http://dx.doi.org/10.3389/fcvm.2022.862118 Text en Copyright © 2022 Di Mattía, Díaz Zegarra, Valverde, Blanco, Jaquenod De Giusti, Portiansky, Aiello and Orlowski. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Di Mattía, Romina A. Díaz Zegarra, Leandro A. Valverde, Carlos A. Blanco, Paula G. Jaquenod De Giusti, Carolina Portiansky, Enrique L. Aiello, Ernesto A. Orlowski, Alejandro In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice |
title | In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice |
title_full | In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice |
title_fullStr | In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice |
title_full_unstemmed | In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice |
title_short | In vivo Overexpression of Electrogenic Sodium/Bicarbonate Cotransporter (NBCe1) by AAV9 Modifies the Cardiac Action Potential and the QT Interval in Mice |
title_sort | in vivo overexpression of electrogenic sodium/bicarbonate cotransporter (nbce1) by aav9 modifies the cardiac action potential and the qt interval in mice |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082548/ https://www.ncbi.nlm.nih.gov/pubmed/35548416 http://dx.doi.org/10.3389/fcvm.2022.862118 |
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