Jiménez Sábado, VerónicaCasabella-Ramón, SergiLlach, AnnaGich, IgnasiCasellas, SandraCiruela Alférez, FranciscoChen, S.R. WayneGuerra, José MaríaGinel, AntoninoBenítez, RaulCinca, JuanTarifa, CarmenHove-Madsen, Leif2025-11-062025-11-062023-02-010753-3322https://hdl.handle.net/2445/224177Aims: 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.11 p.application/pdfengcc by-nc-nd (c) Jiménez Sábado, Verónica et al., 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/Beta-blocadorsFibril·lació auricularCalciMonofosfat d'adenosina cíclicAdrenergic beta blockersAtrial fibrillationCalciumAdenylic acidinfo:eu-repo/semantics/article7283502025-11-06info:eu-repo/semantics/openAccess36592495