Beta-blocker treatment of patients with atrial fibrillation attenuates spontaneous calcium release-induced electrical activity.
Biomed Pharmacother
; 158: 114169, 2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36592495
ABSTRACT
AIMS:
Atrial fibrillation (AF) has been associated with excessive spontaneous calcium release, linked to cyclic AMP (cAMP)-dependent phosphorylation of calcium regulatory proteins. Because ß-blockers are expected to attenuate cAMP-dependent signaling, we aimed to examine whether the treatment of patients with ß-blockers affected the incidence of spontaneous calcium release events or transient inward currents (ITI).METHODS:
The impact of treatment with commonly used ß-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 factorsRESULTS:
The L-type calcium current (ICa) density was diminished significantly in patients with chronic but not paroxysmal AF and the treatment of patients with ß-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 ß-blocker treatment reduced the frequency to levels observed in patients without AF. Confocal calcium imaging showed that ß-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 ß-blockers.CONCLUSION:
Together, our findings demonstrate that ß-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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Cálcio
/
Antagonistas Adrenérgicos beta
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article