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2023-02-01

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cc by-nc-nd (c) Jiménez Sábado, Verónica et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224177

Beta-blocker treatment of patients with atrial fibrillation attenuates abnormal electrical activity induced by spontaneous calcium release

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Recurs relacionat

https://doi.org/10.1016/j.biopha.2022.114169

Resum

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.

Matèries

Beta-blocadors, Fibril·lació auricular, Calci, Monofosfat d'adenosina cíclic

Matèries (anglès)

Adrenergic beta blockers, Atrial fibrillation, Calcium, Adenylic acid

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Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

JIMÉNEZ SÁBADO, Verónica, et al. Beta-blocker treatment of patients with atrial fibrillation attenuates abnormal electrical activity induced by spontaneous calcium release. Biomedicine & Pharmacotherapy. 2023. Vol. 158. ISSN 0753-3322. [consulted: 14 of August of 2026]. Available at: https://hdl.handle.net/2445/224177

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