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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/84354
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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 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/10915/84354 |
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 |
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