Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes

A hallmark of atrial fibrillation is an excess of spontaneous calcium release events, which can be mimicked by beta 1- or beta 2-adrenergic stimulation. Because beta 1-adrenergic receptor blockers (beta 1-blockers) are primarily used in clinical practice, we here examined the impact of beta 2-adrene...

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Autores: Casabella-Ramon, S, Jimenez-Sabado, V, Tarifa, C, Casellas, S, Lu, TT, Izquierdo-Castro, P, Gich, I, Jimenez, M, Ginel, A, Guerra, JM, Chen, SRW, Benitez, R, Hove-Madsen, L
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p23573
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23573
Access Level:acceso abierto
Palabra clave:beta-adrenergic receptor blocker
human atrial myocyte
sarcoplasmic reticulum
calcium spark
arrhythmia
carvedilol
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spelling Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial MyocytesCasabella-Ramon, SJimenez-Sabado, VTarifa, CCasellas, SLu, TTIzquierdo-Castro, PGich, IJimenez, MGinel, AGuerra, JMChen, SRWBenitez, RHove-Madsen, Lbeta-adrenergic receptor blockerhuman atrial myocytesarcoplasmic reticulumcalcium sparkarrhythmiacarvedilolA hallmark of atrial fibrillation is an excess of spontaneous calcium release events, which can be mimicked by beta 1- or beta 2-adrenergic stimulation. Because beta 1-adrenergic receptor blockers (beta 1-blockers) are primarily used in clinical practice, we here examined the impact of beta 2-adrenergic stimulation on spontaneous calcium release and assessed whether the R- and S-enantiomers of the non-selective beta- blocker carvedilol could reverse these effects. For this purpose, human atrial myocytes were isolated from patients undergoing cardiovascular surgery and subjected to confocal calcium imaging or immunofluorescent labeling of the ryanodine receptor (RyR2). Interestingly, the beta 2-adrenergic agonist fenoterol increased the incidence of calcium sparks and waves to levels observed with the non-specific beta-adrenergic agonist isoproterenol. Moreover, fenoterol increased both the amplitude and duration of the sparks, facilitating their fusion into calcium waves. Subsequent application of the non beta-blocking R-Carvedilol enantiomer reversed these effects of fenoterol in a dose-dependent manner. R-Carvedilol also reversed the fenoterol-induced phosphorylation of the RyR2 at Ser-2808 dose-dependently, and 1 mu M of either R- or S-Carvedilol fully reversed the effect of fenoterol. Together, these findings demonstrate that beta 2-adrenergic stimulation alone stimulates RyR2 phosphorylation at Ser-2808 and spontaneous calcium release maximally, and points to carvedilol as a tool to attenuate the pathological activation of beta 2-receptors.MDPI2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23573BiomedicinesISSN: 22279059reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p235732026-05-27T12:37:41Z
dc.title.none.fl_str_mv Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
title Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
spellingShingle Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
Casabella-Ramon, S
beta-adrenergic receptor blocker
human atrial myocyte
sarcoplasmic reticulum
calcium spark
arrhythmia
carvedilol
title_short Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
title_full Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
title_fullStr Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
title_full_unstemmed Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
title_sort Impact of R-Carvedilol on beta 2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes
dc.creator.none.fl_str_mv Casabella-Ramon, S
Jimenez-Sabado, V
Tarifa, C
Casellas, S
Lu, TT
Izquierdo-Castro, P
Gich, I
Jimenez, M
Ginel, A
Guerra, JM
Chen, SRW
Benitez, R
Hove-Madsen, L
author Casabella-Ramon, S
author_facet Casabella-Ramon, S
Jimenez-Sabado, V
Tarifa, C
Casellas, S
Lu, TT
Izquierdo-Castro, P
Gich, I
Jimenez, M
Ginel, A
Guerra, JM
Chen, SRW
Benitez, R
Hove-Madsen, L
author_role author
author2 Jimenez-Sabado, V
Tarifa, C
Casellas, S
Lu, TT
Izquierdo-Castro, P
Gich, I
Jimenez, M
Ginel, A
Guerra, JM
Chen, SRW
Benitez, R
Hove-Madsen, L
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv beta-adrenergic receptor blocker
human atrial myocyte
sarcoplasmic reticulum
calcium spark
arrhythmia
carvedilol
topic beta-adrenergic receptor blocker
human atrial myocyte
sarcoplasmic reticulum
calcium spark
arrhythmia
carvedilol
description A hallmark of atrial fibrillation is an excess of spontaneous calcium release events, which can be mimicked by beta 1- or beta 2-adrenergic stimulation. Because beta 1-adrenergic receptor blockers (beta 1-blockers) are primarily used in clinical practice, we here examined the impact of beta 2-adrenergic stimulation on spontaneous calcium release and assessed whether the R- and S-enantiomers of the non-selective beta- blocker carvedilol could reverse these effects. For this purpose, human atrial myocytes were isolated from patients undergoing cardiovascular surgery and subjected to confocal calcium imaging or immunofluorescent labeling of the ryanodine receptor (RyR2). Interestingly, the beta 2-adrenergic agonist fenoterol increased the incidence of calcium sparks and waves to levels observed with the non-specific beta-adrenergic agonist isoproterenol. Moreover, fenoterol increased both the amplitude and duration of the sparks, facilitating their fusion into calcium waves. Subsequent application of the non beta-blocking R-Carvedilol enantiomer reversed these effects of fenoterol in a dose-dependent manner. R-Carvedilol also reversed the fenoterol-induced phosphorylation of the RyR2 at Ser-2808 dose-dependently, and 1 mu M of either R- or S-Carvedilol fully reversed the effect of fenoterol. Together, these findings demonstrate that beta 2-adrenergic stimulation alone stimulates RyR2 phosphorylation at Ser-2808 and spontaneous calcium release maximally, and points to carvedilol as a tool to attenuate the pathological activation of beta 2-receptors.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23573
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23573
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Biomedicines
ISSN: 22279059
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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