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

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...

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Autores principales: Mundiña-Weilenmann, Cecilia, Ferrero, Paola Viviana, Said, María Matilde, Vittone, Leticia, Kranias, Evangelia G., Mattiazzi, Alicia Ramona
Formato: Articulo
Lenguaje:Inglés
Publicado: 2005
Materias:
Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84354
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84354
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
spellingShingle Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
Mundiña-Weilenmann, Cecilia
Ferrero, Paola Viviana
Said, María Matilde
Vittone, Leticia
Kranias, Evangelia G.
Mattiazzi, Alicia Ramona
Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
topic_facet Ciencias Médicas
CaMKII
Contractile function
Myocardial acidosis
Na+/Ca2+ exchanger
Phospholamban phosphorylation
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.
format Articulo
Articulo
author Mundiña-Weilenmann, Cecilia
Ferrero, Paola Viviana
Said, María Matilde
Vittone, Leticia
Kranias, Evangelia G.
Mattiazzi, Alicia Ramona
author_facet Mundiña-Weilenmann, Cecilia
Ferrero, Paola Viviana
Said, María Matilde
Vittone, Leticia
Kranias, Evangelia G.
Mattiazzi, Alicia Ramona
author_sort Mundiña-Weilenmann, Cecilia
title Role of phosphorylation of Thr17 residue of phospholamban in mechanical recovery during hypercapnic acidosis
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
publishDate 2005
url http://sedici.unlp.edu.ar/handle/10915/84354
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