Beta-blocker treatment of patients with atrial fibrillation attenuates spontaneous calcium release-induced electrical activity
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 pat...
| Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | article |
| Publication Date: | 2023 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:302803 |
| Online Access: | https://ddd.uab.cat/record/302803 https://dx.doi.org/urn:doi:10.1016/j.biopha.2022.114169 |
| Access Level: | Open access |
| Keyword: | Arrhythmia Calcium currents Calcium sparks Human atrial myocyte Sarcoplasmic reticulum β-blocker treatment |
| Summary: | 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 (I). 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 (I) density was diminished significantly in patients with chronic but not paroxysmal AF and the treatment of patients with β-blockers did not affect I density in any group. By contrast, the I 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 I density. |
|---|