Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Ef...

Autores
Gonano, Luis Alberto; Vila Petroff, Martin Gerarde
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cardiotonic glycosides or digitalis are positive inotropes used in clinical practice for the treatment of heart failure, which also exist as endogenous ligands of the Na+ /K+ ATPase. An increase in the intracellular Ca2+ content mediates their positive inotropic effect, but has also been proposed as a trigger of life-threatening arrhythmias. Although the mechanisms involved in the positive inotropic effect of these compounds have been extensively studied, those underlying their arrhythmogenic action remain ill defined. Recent evidence has placed posttranslational modifications of the ryanodine receptor (RyR2), leading to arrhythmogenic Ca2+ release, in the centre of the storm. In this review we will examine, in depth, the mechanisms that generate the arrhythmogenic substrate, focussing on the role played by the RyR2 and how its CaMKII-dependent regulation may shift the balance from an inotropic to an arrhythmogenic Ca2+ release. Finally, we will provide evidence suggesting that stabilising RyR2 function could result in a potential new strategy to prevent cardiotonic glycoside-induced arrhythmias that could lead to a safer and more extensive use of these compounds.
Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Materia
Arrhythmia
Camkii
Calcium Handling
Cardiotonic Glycosides
Ryr2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25025
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/25025
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic EffectGonano, Luis AlbertoVila Petroff, Martin GerardeArrhythmiaCamkiiCalcium HandlingCardiotonic GlycosidesRyr2https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cardiotonic glycosides or digitalis are positive inotropes used in clinical practice for the treatment of heart failure, which also exist as endogenous ligands of the Na+ /K+ ATPase. An increase in the intracellular Ca2+ content mediates their positive inotropic effect, but has also been proposed as a trigger of life-threatening arrhythmias. Although the mechanisms involved in the positive inotropic effect of these compounds have been extensively studied, those underlying their arrhythmogenic action remain ill defined. Recent evidence has placed posttranslational modifications of the ryanodine receptor (RyR2), leading to arrhythmogenic Ca2+ release, in the centre of the storm. In this review we will examine, in depth, the mechanisms that generate the arrhythmogenic substrate, focussing on the role played by the RyR2 and how its CaMKII-dependent regulation may shift the balance from an inotropic to an arrhythmogenic Ca2+ release. Finally, we will provide evidence suggesting that stabilising RyR2 function could result in a potential new strategy to prevent cardiotonic glycoside-induced arrhythmias that could lead to a safer and more extensive use of these compounds.Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaElsevier Science Inc2014-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25025Gonano, Luis Alberto; Vila Petroff, Martin Gerarde; Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect; Elsevier Science Inc; Heart, Lung And Circulation; 23; 12; 7-2014; 1118-11241443-95061444-2892CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.hlc.2014.07.074info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1443950614006532info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:52Zoai:ri.conicet.gov.ar:11336/25025instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:06:52.595CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
title Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
spellingShingle Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
Gonano, Luis Alberto
Arrhythmia
Camkii
Calcium Handling
Cardiotonic Glycosides
Ryr2
title_short Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
title_full Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
title_fullStr Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
title_full_unstemmed Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
title_sort Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect
dc.creator.none.fl_str_mv Gonano, Luis Alberto
Vila Petroff, Martin Gerarde
author Gonano, Luis Alberto
author_facet Gonano, Luis Alberto
Vila Petroff, Martin Gerarde
author_role author
author2 Vila Petroff, Martin Gerarde
author2_role author
dc.subject.none.fl_str_mv Arrhythmia
Camkii
Calcium Handling
Cardiotonic Glycosides
Ryr2
topic Arrhythmia
Camkii
Calcium Handling
Cardiotonic Glycosides
Ryr2
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cardiotonic glycosides or digitalis are positive inotropes used in clinical practice for the treatment of heart failure, which also exist as endogenous ligands of the Na+ /K+ ATPase. An increase in the intracellular Ca2+ content mediates their positive inotropic effect, but has also been proposed as a trigger of life-threatening arrhythmias. Although the mechanisms involved in the positive inotropic effect of these compounds have been extensively studied, those underlying their arrhythmogenic action remain ill defined. Recent evidence has placed posttranslational modifications of the ryanodine receptor (RyR2), leading to arrhythmogenic Ca2+ release, in the centre of the storm. In this review we will examine, in depth, the mechanisms that generate the arrhythmogenic substrate, focussing on the role played by the RyR2 and how its CaMKII-dependent regulation may shift the balance from an inotropic to an arrhythmogenic Ca2+ release. Finally, we will provide evidence suggesting that stabilising RyR2 function could result in a potential new strategy to prevent cardiotonic glycoside-induced arrhythmias that could lead to a safer and more extensive use of these compounds.
Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
description Cardiotonic glycosides or digitalis are positive inotropes used in clinical practice for the treatment of heart failure, which also exist as endogenous ligands of the Na+ /K+ ATPase. An increase in the intracellular Ca2+ content mediates their positive inotropic effect, but has also been proposed as a trigger of life-threatening arrhythmias. Although the mechanisms involved in the positive inotropic effect of these compounds have been extensively studied, those underlying their arrhythmogenic action remain ill defined. Recent evidence has placed posttranslational modifications of the ryanodine receptor (RyR2), leading to arrhythmogenic Ca2+ release, in the centre of the storm. In this review we will examine, in depth, the mechanisms that generate the arrhythmogenic substrate, focussing on the role played by the RyR2 and how its CaMKII-dependent regulation may shift the balance from an inotropic to an arrhythmogenic Ca2+ release. Finally, we will provide evidence suggesting that stabilising RyR2 function could result in a potential new strategy to prevent cardiotonic glycoside-induced arrhythmias that could lead to a safer and more extensive use of these compounds.
publishDate 2014
dc.date.none.fl_str_mv 2014-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25025
Gonano, Luis Alberto; Vila Petroff, Martin Gerarde; Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect; Elsevier Science Inc; Heart, Lung And Circulation; 23; 12; 7-2014; 1118-1124
1443-9506
1444-2892
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25025
identifier_str_mv Gonano, Luis Alberto; Vila Petroff, Martin Gerarde; Subcellular Mechanisms Underlying Digitalis-Induced Arrhythmias: Role of Calcium/Calmodulin-Dependent Kinase II (CaMKII) in the Transition from an Inotropic to an Arrhythmogenic Effect; Elsevier Science Inc; Heart, Lung And Circulation; 23; 12; 7-2014; 1118-1124
1443-9506
1444-2892
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.hlc.2014.07.074
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1443950614006532
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269978241269760
score 13.13397

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