Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II

Autores
Said, María Matilde; Becerra, Romina Valeria; Palomeque, Julieta; Rinaldi, Gustavo; Kaetzel, M. A.; Diaz-Sylvester, P. L.; Copello, J. A.; Dedman, J. R.; Mundiña-Weilenmann, Cecilia; Vittone, Leticia; Mattiazzi, Alicia Ramona
Año de publicación
2008
Idioma
español castellano
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 mM of the CaMKII inhibitor KN-93, 1 mM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca21 uptake, and 30 nM ryanodine or 45 mM dantrolene, to inhibit SR Ca21 release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr17 site of phospholamban (PT-PLN) and SR Ca21 load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca21 leak, when compared with that of control or with acidosis at the same SR Ca21 content. Ca21 leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca21 load, which appears to be mainly due to the increase in PT-PLN.
Centro de Investigaciones Cardiovasculares
Materia
Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/106844
Acceder
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network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase IISaid, María MatildeBecerra, Romina ValeriaPalomeque, JulietaRinaldi, GustavoKaetzel, M. A.Diaz-Sylvester, P. L.Copello, J. A.Dedman, J. R.Mundiña-Weilenmann, CeciliaVittone, LeticiaMattiazzi, Alicia RamonaCiencias Médicassarcoplasmic reticulumcalcium/calmodulin-dependent protein kinaseReturning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 mM of the CaMKII inhibitor KN-93, 1 mM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca21 uptake, and 30 nM ryanodine or 45 mM dantrolene, to inhibit SR Ca21 release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr17 site of phospholamban (PT-PLN) and SR Ca21 load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca21 leak, when compared with that of control or with acidosis at the same SR Ca21 content. Ca21 leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca21 load, which appears to be mainly due to the increase in PT-PLN.Centro de Investigaciones Cardiovasculares2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfH1669-H1683http://sedici.unlp.edu.ar/handle/10915/106844spainfo:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2593495&blobtype=pdfinfo:eu-repo/semantics/altIdentifier/issn/0363-6135info:eu-repo/semantics/altIdentifier/pmid/18723772info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00010.2008info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T10:56:07Zoai:sedici.unlp.edu.ar:10915/106844Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 10:56:07.911SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
spellingShingle Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
Said, María Matilde
Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
title_short Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_full Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_fullStr Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_full_unstemmed Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
title_sort Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart : Role of Ca2+/calmodulin-dependent protein kinase II
dc.creator.none.fl_str_mv Said, María Matilde
Becerra, Romina Valeria
Palomeque, Julieta
Rinaldi, Gustavo
Kaetzel, M. A.
Diaz-Sylvester, P. L.
Copello, J. A.
Dedman, J. R.
Mundiña-Weilenmann, Cecilia
Vittone, Leticia
Mattiazzi, Alicia Ramona
author Said, María Matilde
author_facet Said, María Matilde
Becerra, Romina Valeria
Palomeque, Julieta
Rinaldi, Gustavo
Kaetzel, M. A.
Diaz-Sylvester, P. L.
Copello, J. A.
Dedman, J. R.
Mundiña-Weilenmann, Cecilia
Vittone, Leticia
Mattiazzi, Alicia Ramona
author_role author
author2 Becerra, Romina Valeria
Palomeque, Julieta
Rinaldi, Gustavo
Kaetzel, M. A.
Diaz-Sylvester, P. L.
Copello, J. A.
Dedman, J. R.
Mundiña-Weilenmann, Cecilia
Vittone, Leticia
Mattiazzi, Alicia Ramona
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
topic Ciencias Médicas
sarcoplasmic reticulum
calcium/calmodulin-dependent protein kinase
dc.description.none.fl_txt_mv Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 mM of the CaMKII inhibitor KN-93, 1 mM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca21 uptake, and 30 nM ryanodine or 45 mM dantrolene, to inhibit SR Ca21 release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr17 site of phospholamban (PT-PLN) and SR Ca21 load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca21 leak, when compared with that of control or with acidosis at the same SR Ca21 content. Ca21 leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca21 load, which appears to be mainly due to the increase in PT-PLN.
Centro de Investigaciones Cardiovasculares
description Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 mM of the CaMKII inhibitor KN-93, 1 mM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca21 uptake, and 30 nM ryanodine or 45 mM dantrolene, to inhibit SR Ca21 release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr17 site of phospholamban (PT-PLN) and SR Ca21 load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca21 leak, when compared with that of control or with acidosis at the same SR Ca21 content. Ca21 leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca21 load, which appears to be mainly due to the increase in PT-PLN.
publishDate 2008
dc.date.none.fl_str_mv 2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/106844
url http://sedici.unlp.edu.ar/handle/10915/106844
dc.language.none.fl_str_mv spa
language spa
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2593495&blobtype=pdf
info:eu-repo/semantics/altIdentifier/issn/0363-6135
info:eu-repo/semantics/altIdentifier/pmid/18723772
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00010.2008
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
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instname_str Universidad Nacional de La Plata
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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