Direct Evidence for the Lack of Role of Thr-17 Phosphorylation of Phospholamban (PLB), on the Frequency-Dependent Acceleration of Relaxation (FDAR) in the Rat Ventricle

MUNDIÑA-WEILENMANN C; SAID M; VALVERDE CA; VITTONE L; MATTIAZZI A

Orlando, USA

Congreso; Scientific Sessions 2003; 2003

American Heart Association

Previous experiments in rat myocytes suggested that phosphorylation of Thr17 residue of PLB is responsible for FDAR (Hagemann, J Biol Chem, 2000). Experiments in PLBKO mice did not support this conclusion (DeSantiago, J Mol Cell Cardiol, 2002). Thus, the relationship between FDAR and PLB phosphorylation remains uncertain. The present experiments re-assess the issue in the intact heart, by comparing the degree of PLB phosphorylation residues associated with a similar acceleration of relaxation evoked either by isoproterenol (IDAR) or by increasing stimulation frequency (FDAR) (Figure). Whereas IDAR occurs tightly associated with a significant increase in the phosphorylation of Ser16 and Thr17 of PLB, (in accordance with the fact that this relaxant effect is mainly dependent on PLB phosphorylation), FDAR occurs without significant changes in the phosphorylation of any of PLB residues. The results provide direct evidence indicating that phosphorylation of PLB does not play any significant role in FDAR in the intact beating heart.