Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis

Autores
Mundiña-Weilenmann, Cecilia; Ferrero, Paola Viviana; Said, María Matilde; Vittone, Leticia; Kranias, Evangelia G.; Mattiazzi, Alicia Ramona
Año de publicación
2005
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: To assess the time course of phosphorylation of phospholamban residues, the underlying mechanisms determining these phosphorylations, and their functional impact on the mechanical recovery during acidosis. Methods: Langendorff perfused rat hearts were submitted to 30 min of hypercapnic acidosis. Contractility, relaxation, and phosphorylation of phospholamban residues, immunodetected by specific antibodies, were determined. Results: Acidosis produced a mechanical impairment followed by a spontaneous recovery, most of which occurred within the first 3 min of acidosis (early recovery). During this period, contractility and relaxation recovered by 67±9% and 77±11%, respectively, from its maximal depression, together with an increase in the Ca2+-calmodulin-dependent protein kinase II (CaMKII)-dependent phosphorylation of Thr17. The CaMKII inhibitor KN-93, at 1, 5 and 10 μM, decreased Thr17 phosphorylation to basal levels and produced a similar impairment of the early relaxation recovery (50%). However, only 5 and 10 μM KN-93 inhibited the early contractile recovery and completely blunted the late mechanical recovery. Inhibition of the reverse mode of the Na+/Ca2+ exchanger by KB-R7943 decreased Thr17 phosphorylation but accelerated the early contractile recovery. Conclusions: CaMKII-dependent Thr17 phosphorylation significantly increased at the beginning of acidosis, is responsible for 50% of the early relaxation recovery, and is linked to the activation of the reverse Na+/Ca2+ mode. The early contractile recovery and the late mechanical recovery are dependent on CaMKII but independent of the phosphorylation of the Thr17 residue of phospholamban. The reverse Na+/Ca2+ mode has an additional negative effect that opposes the early mechanical recovery.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
Materia
Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
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:10915/84354

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network_name_str SEDICI (UNLP)
spelling Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosisMundiña-Weilenmann, CeciliaFerrero, Paola VivianaSaid, María MatildeVittone, LeticiaKranias, Evangelia G.Mattiazzi, Alicia RamonaCiencias MédicasCaMKIIContractile functionMyocardial acidosisNa+/Ca2+ exchangerPhospholamban phosphorylationObjectives: To assess the time course of phosphorylation of phospholamban residues, the underlying mechanisms determining these phosphorylations, and their functional impact on the mechanical recovery during acidosis. Methods: Langendorff perfused rat hearts were submitted to 30 min of hypercapnic acidosis. Contractility, relaxation, and phosphorylation of phospholamban residues, immunodetected by specific antibodies, were determined. Results: Acidosis produced a mechanical impairment followed by a spontaneous recovery, most of which occurred within the first 3 min of acidosis (early recovery). During this period, contractility and relaxation recovered by 67±9% and 77±11%, respectively, from its maximal depression, together with an increase in the Ca<SUP>2+</SUP>-calmodulin-dependent protein kinase II (CaMKII)-dependent phosphorylation of Thr<SUP>17</SUP>. The CaMKII inhibitor KN-93, at 1, 5 and 10 μM, decreased Thr<SUP>17</SUP> phosphorylation to basal levels and produced a similar impairment of the early relaxation recovery (50%). However, only 5 and 10 μM KN-93 inhibited the early contractile recovery and completely blunted the late mechanical recovery. Inhibition of the reverse mode of the Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchanger by KB-R7943 decreased Thr<SUP>17</SUP> phosphorylation but accelerated the early contractile recovery. Conclusions: CaMKII-dependent Thr<SUP>17</SUP> phosphorylation significantly increased at the beginning of acidosis, is responsible for 50% of the early relaxation recovery, and is linked to the activation of the reverse Na<SUP>+</SUP>/Ca<SUP>2+</SUP> mode. The early contractile recovery and the late mechanical recovery are dependent on CaMKII but independent of the phosphorylation of the Thr<SUP>17</SUP> residue of phospholamban. The reverse Na<SUP>+</SUP>/Ca<SUP>2+</SUP> mode has an additional negative effect that opposes the early mechanical recovery.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculares2005info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf114-122http://sedici.unlp.edu.ar/handle/10915/84354enginfo:eu-repo/semantics/altIdentifier/issn/0008-6363info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cardiores.2004.12.028info: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:UNLP2025-09-29T11:16:14Zoai:sedici.unlp.edu.ar:10915/84354Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:15.277SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
title Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
spellingShingle Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
Mundiña-Weilenmann, Cecilia
Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
title_short Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
title_full Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
title_fullStr Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
title_full_unstemmed Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
title_sort Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
dc.creator.none.fl_str_mv Mundiña-Weilenmann, Cecilia
Ferrero, Paola Viviana
Said, María Matilde
Vittone, Leticia
Kranias, Evangelia G.
Mattiazzi, Alicia Ramona
author Mundiña-Weilenmann, Cecilia
author_facet Mundiña-Weilenmann, Cecilia
Ferrero, Paola Viviana
Said, María Matilde
Vittone, Leticia
Kranias, Evangelia G.
Mattiazzi, Alicia Ramona
author_role author
author2 Ferrero, Paola Viviana
Said, María Matilde
Vittone, Leticia
Kranias, Evangelia G.
Mattiazzi, Alicia Ramona
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
topic Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
dc.description.none.fl_txt_mv Objectives: To assess the time course of phosphorylation of phospholamban residues, the underlying mechanisms determining these phosphorylations, and their functional impact on the mechanical recovery during acidosis. Methods: Langendorff perfused rat hearts were submitted to 30 min of hypercapnic acidosis. Contractility, relaxation, and phosphorylation of phospholamban residues, immunodetected by specific antibodies, were determined. Results: Acidosis produced a mechanical impairment followed by a spontaneous recovery, most of which occurred within the first 3 min of acidosis (early recovery). During this period, contractility and relaxation recovered by 67±9% and 77±11%, respectively, from its maximal depression, together with an increase in the Ca<SUP>2+</SUP>-calmodulin-dependent protein kinase II (CaMKII)-dependent phosphorylation of Thr<SUP>17</SUP>. The CaMKII inhibitor KN-93, at 1, 5 and 10 μM, decreased Thr<SUP>17</SUP> phosphorylation to basal levels and produced a similar impairment of the early relaxation recovery (50%). However, only 5 and 10 μM KN-93 inhibited the early contractile recovery and completely blunted the late mechanical recovery. Inhibition of the reverse mode of the Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchanger by KB-R7943 decreased Thr<SUP>17</SUP> phosphorylation but accelerated the early contractile recovery. Conclusions: CaMKII-dependent Thr<SUP>17</SUP> phosphorylation significantly increased at the beginning of acidosis, is responsible for 50% of the early relaxation recovery, and is linked to the activation of the reverse Na<SUP>+</SUP>/Ca<SUP>2+</SUP> mode. The early contractile recovery and the late mechanical recovery are dependent on CaMKII but independent of the phosphorylation of the Thr<SUP>17</SUP> residue of phospholamban. The reverse Na<SUP>+</SUP>/Ca<SUP>2+</SUP> mode has an additional negative effect that opposes the early mechanical recovery.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
description Objectives: To assess the time course of phosphorylation of phospholamban residues, the underlying mechanisms determining these phosphorylations, and their functional impact on the mechanical recovery during acidosis. Methods: Langendorff perfused rat hearts were submitted to 30 min of hypercapnic acidosis. Contractility, relaxation, and phosphorylation of phospholamban residues, immunodetected by specific antibodies, were determined. Results: Acidosis produced a mechanical impairment followed by a spontaneous recovery, most of which occurred within the first 3 min of acidosis (early recovery). During this period, contractility and relaxation recovered by 67±9% and 77±11%, respectively, from its maximal depression, together with an increase in the Ca<SUP>2+</SUP>-calmodulin-dependent protein kinase II (CaMKII)-dependent phosphorylation of Thr<SUP>17</SUP>. The CaMKII inhibitor KN-93, at 1, 5 and 10 μM, decreased Thr<SUP>17</SUP> phosphorylation to basal levels and produced a similar impairment of the early relaxation recovery (50%). However, only 5 and 10 μM KN-93 inhibited the early contractile recovery and completely blunted the late mechanical recovery. Inhibition of the reverse mode of the Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchanger by KB-R7943 decreased Thr<SUP>17</SUP> phosphorylation but accelerated the early contractile recovery. Conclusions: CaMKII-dependent Thr<SUP>17</SUP> phosphorylation significantly increased at the beginning of acidosis, is responsible for 50% of the early relaxation recovery, and is linked to the activation of the reverse Na<SUP>+</SUP>/Ca<SUP>2+</SUP> mode. The early contractile recovery and the late mechanical recovery are dependent on CaMKII but independent of the phosphorylation of the Thr<SUP>17</SUP> residue of phospholamban. The reverse Na<SUP>+</SUP>/Ca<SUP>2+</SUP> mode has an additional negative effect that opposes the early mechanical recovery.
publishDate 2005
dc.date.none.fl_str_mv 2005
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/84354
url http://sedici.unlp.edu.ar/handle/10915/84354
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0008-6363
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cardiores.2004.12.028
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
114-122
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instname:Universidad Nacional de La Plata
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