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dc.date.accessioned 2021-10-26T13:28:25Z
dc.date.available 2021-10-26T13:28:25Z
dc.date.issued 2005-02
dc.identifier.uri http://sedici.unlp.edu.ar/handle/10915/127258
dc.description.abstract An increase in stimulation frequency causes an acceleration of myocardial relaxation (FDAR). Several mechanisms have been postulated to explain this effect, among which is the Ca²⁺–calmodulin-dependent protein kinase (CaMKII)-dependent phosphorylation of the Thr¹⁷ site of phospholamban (PLN). To gain further insights into the mechanisms of FDAR, we studied the FDAR and the phosphorylation of PLN residues in perfused rat hearts, cat papillary muscles and isolated cat myocytes. This allowed us to sweep over a wide range of frequencies, in species with either positive or negative force–frequency relationships, as well as to explore the FDAR under isometric (or isovolumic) and isotonic conditions. Results were compared with those produced by isoprenaline, an intervention known to accelerate relaxation (IDAR) via PLN phosphorylation. While IDAR occurs tightly associated with a significant increase in the phosphorylation of Ser¹⁶ and Thr¹⁷ of PLN, FDAR occurs without significant changes in the phosphorylation of PLN residues in the intact heart and cat papillary muscles. Moreover, in intact hearts, FDAR was not associated with any significant change in the CaMKII-dependent phosphorylation of sarcoplasmic/endoplasmic Ca²⁺ ATPase (SERCA2a), and was not affected by the presence of the CaMKII inhibitor, KN-93. In isolated myocytes, FDAR occurred associated with an increase in Thr¹⁷ phosphorylation. However, for a similar relaxant effect produced by isoprenaline, the phosphorylation of PLN (Ser¹⁶ and Thr¹⁷) was significantly higher in the presence of the β-agonist. Moreover, the time course of Thr¹⁷ phosphorylation was significantly delayed with respect to the onset of FDAR. In contrast, the time course of Ser¹⁶ phosphorylation, the first residue that becomes phosphorylated with isoprenaline, was temporally associated with IDAR. Furthermore, KN-93 significantly decreased the phosphorylation of Thr¹⁷ that was evoked by increasing the stimulation frequency, but failed to affect FDAR. Taken together, the results provide direct evidence indicating that CaMKII phosphorylation pathways are not involved in FDAR and that FDAR and IDAR do not share a common underlying mechanism. More likely, a CaMKII-independent mechanism could be involved, whereby increasing stimulation frequency would disrupt the SERCA2a–PLN interaction, leading to an increase in SR Ca²⁺ uptake and myocardial relaxation. en
dc.format.extent 801-813 es
dc.language en es
dc.subject myocardial relaxation es
dc.subject phosphorylation es
dc.subject isoprenaline es
dc.subject mammalian heart es
dc.subject phospholamban es
dc.title Frequency-dependent acceleration of relaxation in mammalian heart: a property not relying on phospholamban and SERCA2a phosphorylation en
dc.type Articulo es
sedici.identifier.other doi:10.1113/jphysiol.2004.075432 es
sedici.identifier.issn 0022-3751 es
sedici.identifier.issn 1469-7793 es
sedici.creator.person Valverde, Carlos Alfredo es
sedici.creator.person Mundiña-Weilenmann, Cecilia es
sedici.creator.person Said, María Matilde es
sedici.creator.person Ferrero, Paola Viviana es
sedici.creator.person Vittone, Leticia Beatriz es
sedici.creator.person Salas, Margarita Ana es
sedici.creator.person Palomeque, Julieta es
sedici.creator.person Vila Petroff, Martín Gerardo es
sedici.creator.person Mattiazzi, Alicia Ramona es
sedici.subject.materias Medicina es
sedici.description.fulltext true es
mods.originInfo.place Facultad de Ciencias Médicas es
mods.originInfo.place Centro de Investigaciones Cardiovasculares es
sedici.subtype Articulo es
sedici.rights.license Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
sedici.rights.uri http://creativecommons.org/licenses/by-nc-sa/4.0/
sedici.description.peerReview peer-review es
sedici.relation.journalTitle The Journal of Physiology es
sedici.relation.journalVolumeAndIssue vol. 562, no. 3 es


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Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) Excepto donde se diga explícitamente, este item se publica bajo la siguiente licencia Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)