2026-04-17T01:47:26Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2241772025-12-05T00:12:45Zcom_2072_1057col_2072_478916col_2072_478917col_2072_478929

urn:hdl:2445/224177 Beta-blocker treatment of patients with atrial fibrillation attenuates abnormal electrical activity induced by spontaneous calcium release Jiménez Sábado, Verónica Casabella-Ramón, Sergi Llach, Anna Gich, Ignasi Casellas, Sandra Ciruela Alférez, Francisco Chen, S.R. Wayne Guerra, José María Ginel, Antonino Benítez, Raul Cinca, Juan Tarifa, Carmen Hove-Madsen, Leif Beta-blocadors Fibril·lació auricular Calci Monofosfat d'adenosina cíclic Adrenergic beta blockers Atrial fibrillation Calcium Adenylic acid Aims: Atrial fibrillation (AF) has been associated with excessive spontaneous calcium release, linked to cyclic AMP (cAMP)-dependent phosphorylation of calcium regulatory proteins. Because β-blockers are expected to attenuate cAMP-dependent signaling, we aimed to examine whether the treatment of patients with β-blockers affected the incidence of spontaneous calcium release events or transient inward currents (ITI). Methods: The impact of treatment with commonly used β-blockers was analyzed in human atrial myocytes from 371 patients using patch-clamp technique, confocal calcium imaging or immunofluorescent labeling. Data were analyzed using multivariate regression analysis taking into account potentially confounding effects of relevant clinical factors RESULTS: The L-type calcium current (ICa) density was diminished significantly in patients with chronic but not paroxysmal AF and the treatment of patients with β-blockers did not affect ICa density in any group. By contrast, the ITI frequency was elevated in patients with either paroxysmal or chronic AF that did not receive treatment, and β-blocker treatment reduced the frequency to levels observed in patients without AF. Confocal calcium imaging showed that β-blocker treatment also reduced the calcium spark frequency in patients with AF to levels observed in those without AF. Furthermore, phosphorylation of the ryanodine receptor (RyR2) at Ser-2808 and phospholamban at Ser-16 was significantly lower in patients with AF that received β-blockers. Conclusion: Together, our findings demonstrate that β-blocker treatment may be of therapeutic utility to prevent spontaneous calcium release-induced atrial electrical activity; especially in patients with a history of paroxysmal AF displaying preserved ICa density. 2025-11-06T18:54:37Z 2025-11-06T18:54:37Z 2023-02-01 2025-11-06T18:54:37Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1016/j.biopha.2022.114169 Biomedicine & Pharmacotherapy, 2023, vol. 158 https://doi.org/10.1016/j.biopha.2022.114169 cc by-nc-nd (c) Jiménez Sábado, Verónica et al., 2023 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Elsevier Masson SAS Articles publicats en revistes (Patologia i Terapèutica Experimental)