Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart

Objective: To investigate the importance of the phosphorylation of Ser16 and Thr17 sites of phospholamban (PLN) on intracellular Ca2+ (Cai2+) handling and contractile recovery of the stunned myocardium. Methods: Cai2+ (Rhod-2, pulsed local-field fluorescence microscopy) and contractility (isovolumic...

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Autores principales: Valverde, Carlos Alfredo, Mundiña-Weilenmann, Cecilia, Reyes, Mariano, Kranias, Evangelia G., Escobar, Ariel L., Mattiazzi, Alicia Ramona
Formato: Articulo
Lenguaje:Inglés
Publicado: 2006
Materias:
Ciencias Médicas
Intracellular calcium
Ischemia-reperfusion
Myofibrillar proteins
Phospholamban mutants
Phospholamban phosphorylation residues
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83099
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-83099
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
Intracellular calcium
Ischemia-reperfusion
Myofibrillar proteins
Phospholamban mutants
Phospholamban phosphorylation residues
spellingShingle Ciencias Médicas
Intracellular calcium
Ischemia-reperfusion
Myofibrillar proteins
Phospholamban mutants
Phospholamban phosphorylation residues
Valverde, Carlos Alfredo
Mundiña-Weilenmann, Cecilia
Reyes, Mariano
Kranias, Evangelia G.
Escobar, Ariel L.
Mattiazzi, Alicia Ramona
Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart
topic_facet Ciencias Médicas
Intracellular calcium
Ischemia-reperfusion
Myofibrillar proteins
Phospholamban mutants
Phospholamban phosphorylation residues
description Objective: To investigate the importance of the phosphorylation of Ser16 and Thr17 sites of phospholamban (PLN) on intracellular Ca2+ (Cai2+) handling and contractile recovery of the stunned myocardium. Methods: Cai2+ (Rhod-2, pulsed local-field fluorescence microscopy) and contractility (isovolumic left ventricular developed pressure, LVDP) were simultaneously measured in Langendorff perfused hearts from transgenic mice expressing either intact PLN (PLN-WT) or PLN with both phosphorylation sites mutated to Ala (PLN-DM), subjected to 12 min of global ischemia followed by a reperfusion period of 30 min. Results: Pre-ischemic values of Cai2+ and LVDP were similar in both groups. In PLN-WT, a transient increase in Thr17 phosphorylation at early reperfusion preceded a recovery of Ca2+ transient amplitude, virtually completed by the end of reperfusion. LVDP at 30 min reperfusion was 67.9 ± 7.6% of pre-ischemic values, n = 14. In contrast, in PLN-DM, there was a poor recovery of Cai2+ transient amplitude and LVDP was significantly lower (28.3 ± 6.7%, n = 11, 30 min reperfusion) than in PLN-WT hearts. Although myofilament Ca2+ responsiveness and troponin I (TnI) degradation did not differ between groups, the episodes of mechanical alternans, typical of Cai2+ overload, were significantly prolonged in PLN-DM vs. PLN-WT hearts. Conclusions: PLN phosphorylation appears to be crucial for the mechanical and Cai2+ recovery during stunning and protective against the mechanical abnormalities typical of Cai2+ overload. The importance of PLN phosphorylation would primarily reside in the Thr17 residue, which is phosphorylated during the critical early phase of reperfusion. Our results emphasize that, although ablation of PLN phosphorylation does not affect basal contractility, it does alter Ca2+ handling and mechanical performance under stress situations.
format Articulo
Articulo
author Valverde, Carlos Alfredo
Mundiña-Weilenmann, Cecilia
Reyes, Mariano
Kranias, Evangelia G.
Escobar, Ariel L.
Mattiazzi, Alicia Ramona
author_facet Valverde, Carlos Alfredo
Mundiña-Weilenmann, Cecilia
Reyes, Mariano
Kranias, Evangelia G.
Escobar, Ariel L.
Mattiazzi, Alicia Ramona
author_sort Valverde, Carlos Alfredo
title Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart
title_short Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart
title_full Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart
title_fullStr Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart
title_full_unstemmed Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart
title_sort phospholamban phosphorylation sites enhance the recovery of intracellular ca2+ after perfusion arrest in isolated, perfused mouse heart
publishDate 2006
url http://sedici.unlp.edu.ar/handle/10915/83099
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