Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model

Autores
Lascano, Elena Catalina; Said, Maria Matilde; Vittone, Leticia Beatriz; Mattiazzi, Ramona Alicia; Mundiña, Cecilia Beatriz; Negroni, Jorge Antonio
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Postacidotic arrhythmias have been associated to increased sarcoplasmic reticulum (SR) Ca2 + load and Ca2 +/calmodulin-dependent protein kinase II (CaMKII) activation. However, the molecular mechanisms underlying these arrhythmias are still unclear. To better understand this process, acidosis produced by CO2 increase from 5% to 30%, resulting in intracellular pH (pHi) change from 7.15 to 6.7, was incorporated into a myocyte model of excitation-contraction coupling and contractility, including acidotic inhibition of L-type Ca2 + channel (ICaL), Na+–Ca2 + exchanger, Ca2 + release through the SR ryanodine receptor (RyR2) (Irel), Ca2 + reuptake by the SR Ca2 + ATPase2a (Iup), Na+–K+ pump, K+ efflux through the inward rectifier K+ channel and the transient outward K+ flow (Ito) together with increased activity of the Na+–H+ exchanger (INHE). Simulated CaMKII regulation affecting Irel, Iup, ICaL, INHE and Ito was introduced in the model to partially compensate the acidosis outcome. Late Na+ current increase by CaMKII was also incorporated. Using this scheme and assuming that diastolic Ca2 + leak through the RyR2 was modulated by the resting state of this channel and the difference between SR and dyadic cleft [Ca2 +], postacidotic delayed after depolarizations (DADs) were triggered upon returning to normal pHi after 6 min acidosis. The model showed that DADs depend on SR Ca2 + load and on increased Ca2 + leak through RyR2. This postacidotic arrhythmogenic pattern relies mainly on CaMKII effect on ICaL and Iup, since its individual elimination produced the highest DAD reduction. The model further revealed that during the return to normal pHi, DADs are fully determined by SR Ca2 + load at the end of acidosis. Thereafter, DADs are maintained by SR Ca2 + reloading by Ca2 + influx through the reverse NCX mode during the time period in which [Na+]i is elevated.
Fil: Lascano, Elena Catalina. Fundacion Favaloro; Argentina
Fil: Said, Maria Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Mattiazzi, Ramona Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Mundiña, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Negroni, Jorge Antonio. Fundacion Favaloro; Argentina
Materia
CAMKII
MYOCYTE MODEL
POST ACIDOTIC ARRHYTHMOGENESIS
SARCOPLASMIC RETICULUM CA2+ LEAK
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:11336/11954
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/11954
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte modelLascano, Elena CatalinaSaid, Maria MatildeVittone, Leticia BeatrizMattiazzi, Ramona AliciaMundiña, Cecilia BeatrizNegroni, Jorge AntonioCAMKIIMYOCYTE MODELPOST ACIDOTIC ARRHYTHMOGENESISSARCOPLASMIC RETICULUM CA2+ LEAKhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Postacidotic arrhythmias have been associated to increased sarcoplasmic reticulum (SR) Ca2 + load and Ca2 +/calmodulin-dependent protein kinase II (CaMKII) activation. However, the molecular mechanisms underlying these arrhythmias are still unclear. To better understand this process, acidosis produced by CO2 increase from 5% to 30%, resulting in intracellular pH (pHi) change from 7.15 to 6.7, was incorporated into a myocyte model of excitation-contraction coupling and contractility, including acidotic inhibition of L-type Ca2 + channel (ICaL), Na+–Ca2 + exchanger, Ca2 + release through the SR ryanodine receptor (RyR2) (Irel), Ca2 + reuptake by the SR Ca2 + ATPase2a (Iup), Na+–K+ pump, K+ efflux through the inward rectifier K+ channel and the transient outward K+ flow (Ito) together with increased activity of the Na+–H+ exchanger (INHE). Simulated CaMKII regulation affecting Irel, Iup, ICaL, INHE and Ito was introduced in the model to partially compensate the acidosis outcome. Late Na+ current increase by CaMKII was also incorporated. Using this scheme and assuming that diastolic Ca2 + leak through the RyR2 was modulated by the resting state of this channel and the difference between SR and dyadic cleft [Ca2 +], postacidotic delayed after depolarizations (DADs) were triggered upon returning to normal pHi after 6 min acidosis. The model showed that DADs depend on SR Ca2 + load and on increased Ca2 + leak through RyR2. This postacidotic arrhythmogenic pattern relies mainly on CaMKII effect on ICaL and Iup, since its individual elimination produced the highest DAD reduction. The model further revealed that during the return to normal pHi, DADs are fully determined by SR Ca2 + load at the end of acidosis. Thereafter, DADs are maintained by SR Ca2 + reloading by Ca2 + influx through the reverse NCX mode during the time period in which [Na+]i is elevated.Fil: Lascano, Elena Catalina. Fundacion Favaloro; ArgentinaFil: Said, Maria Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Mattiazzi, Ramona Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Mundiña, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Negroni, Jorge Antonio. Fundacion Favaloro; ArgentinaAcademic Press Ltd - Elsevier Science Ltd2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/11954Lascano, Elena Catalina; Said, Maria Matilde; Vittone, Leticia Beatriz; Mattiazzi, Ramona Alicia; Mundiña, Cecilia Beatriz; et al.; Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 60; 1; 7-2013; 172-1830022-2828enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2013.04.018info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022282813001491info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:35Zoai:ri.conicet.gov.ar:11336/11954instacron: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 10:04:35.673CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
title Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
spellingShingle Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
Lascano, Elena Catalina
CAMKII
MYOCYTE MODEL
POST ACIDOTIC ARRHYTHMOGENESIS
SARCOPLASMIC RETICULUM CA2+ LEAK
title_short Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
title_full Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
title_fullStr Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
title_full_unstemmed Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
title_sort Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model
dc.creator.none.fl_str_mv Lascano, Elena Catalina
Said, Maria Matilde
Vittone, Leticia Beatriz
Mattiazzi, Ramona Alicia
Mundiña, Cecilia Beatriz
Negroni, Jorge Antonio
author Lascano, Elena Catalina
author_facet Lascano, Elena Catalina
Said, Maria Matilde
Vittone, Leticia Beatriz
Mattiazzi, Ramona Alicia
Mundiña, Cecilia Beatriz
Negroni, Jorge Antonio
author_role author
author2 Said, Maria Matilde
Vittone, Leticia Beatriz
Mattiazzi, Ramona Alicia
Mundiña, Cecilia Beatriz
Negroni, Jorge Antonio
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CAMKII
MYOCYTE MODEL
POST ACIDOTIC ARRHYTHMOGENESIS
SARCOPLASMIC RETICULUM CA2+ LEAK
topic CAMKII
MYOCYTE MODEL
POST ACIDOTIC ARRHYTHMOGENESIS
SARCOPLASMIC RETICULUM CA2+ LEAK
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Postacidotic arrhythmias have been associated to increased sarcoplasmic reticulum (SR) Ca2 + load and Ca2 +/calmodulin-dependent protein kinase II (CaMKII) activation. However, the molecular mechanisms underlying these arrhythmias are still unclear. To better understand this process, acidosis produced by CO2 increase from 5% to 30%, resulting in intracellular pH (pHi) change from 7.15 to 6.7, was incorporated into a myocyte model of excitation-contraction coupling and contractility, including acidotic inhibition of L-type Ca2 + channel (ICaL), Na+–Ca2 + exchanger, Ca2 + release through the SR ryanodine receptor (RyR2) (Irel), Ca2 + reuptake by the SR Ca2 + ATPase2a (Iup), Na+–K+ pump, K+ efflux through the inward rectifier K+ channel and the transient outward K+ flow (Ito) together with increased activity of the Na+–H+ exchanger (INHE). Simulated CaMKII regulation affecting Irel, Iup, ICaL, INHE and Ito was introduced in the model to partially compensate the acidosis outcome. Late Na+ current increase by CaMKII was also incorporated. Using this scheme and assuming that diastolic Ca2 + leak through the RyR2 was modulated by the resting state of this channel and the difference between SR and dyadic cleft [Ca2 +], postacidotic delayed after depolarizations (DADs) were triggered upon returning to normal pHi after 6 min acidosis. The model showed that DADs depend on SR Ca2 + load and on increased Ca2 + leak through RyR2. This postacidotic arrhythmogenic pattern relies mainly on CaMKII effect on ICaL and Iup, since its individual elimination produced the highest DAD reduction. The model further revealed that during the return to normal pHi, DADs are fully determined by SR Ca2 + load at the end of acidosis. Thereafter, DADs are maintained by SR Ca2 + reloading by Ca2 + influx through the reverse NCX mode during the time period in which [Na+]i is elevated.
Fil: Lascano, Elena Catalina. Fundacion Favaloro; Argentina
Fil: Said, Maria Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Mattiazzi, Ramona Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Mundiña, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Negroni, Jorge Antonio. Fundacion Favaloro; Argentina
description Postacidotic arrhythmias have been associated to increased sarcoplasmic reticulum (SR) Ca2 + load and Ca2 +/calmodulin-dependent protein kinase II (CaMKII) activation. However, the molecular mechanisms underlying these arrhythmias are still unclear. To better understand this process, acidosis produced by CO2 increase from 5% to 30%, resulting in intracellular pH (pHi) change from 7.15 to 6.7, was incorporated into a myocyte model of excitation-contraction coupling and contractility, including acidotic inhibition of L-type Ca2 + channel (ICaL), Na+–Ca2 + exchanger, Ca2 + release through the SR ryanodine receptor (RyR2) (Irel), Ca2 + reuptake by the SR Ca2 + ATPase2a (Iup), Na+–K+ pump, K+ efflux through the inward rectifier K+ channel and the transient outward K+ flow (Ito) together with increased activity of the Na+–H+ exchanger (INHE). Simulated CaMKII regulation affecting Irel, Iup, ICaL, INHE and Ito was introduced in the model to partially compensate the acidosis outcome. Late Na+ current increase by CaMKII was also incorporated. Using this scheme and assuming that diastolic Ca2 + leak through the RyR2 was modulated by the resting state of this channel and the difference between SR and dyadic cleft [Ca2 +], postacidotic delayed after depolarizations (DADs) were triggered upon returning to normal pHi after 6 min acidosis. The model showed that DADs depend on SR Ca2 + load and on increased Ca2 + leak through RyR2. This postacidotic arrhythmogenic pattern relies mainly on CaMKII effect on ICaL and Iup, since its individual elimination produced the highest DAD reduction. The model further revealed that during the return to normal pHi, DADs are fully determined by SR Ca2 + load at the end of acidosis. Thereafter, DADs are maintained by SR Ca2 + reloading by Ca2 + influx through the reverse NCX mode during the time period in which [Na+]i is elevated.
publishDate 2013
dc.date.none.fl_str_mv 2013-07
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/11336/11954
Lascano, Elena Catalina; Said, Maria Matilde; Vittone, Leticia Beatriz; Mattiazzi, Ramona Alicia; Mundiña, Cecilia Beatriz; et al.; Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 60; 1; 7-2013; 172-183
0022-2828
url http://hdl.handle.net/11336/11954
identifier_str_mv Lascano, Elena Catalina; Said, Maria Matilde; Vittone, Leticia Beatriz; Mattiazzi, Ramona Alicia; Mundiña, Cecilia Beatriz; et al.; Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 60; 1; 7-2013; 172-183
0022-2828
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2013.04.018
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022282813001491
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
dc.publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
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
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score 13.13397

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