跳轉至內容
Merck
  • Beta-blocker treatment of patients with atrial fibrillation attenuates spontaneous calcium release-induced electrical activity.

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

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2023-01-03)
Verónica Jiménez-Sábado, Sergi Casabella-Ramón, Anna Llach, Ignasi Gich, Sandra Casellas, Francisco Ciruela, S R Wayne Chen, José M Guerra, Antonino Ginel, Raúl Benítez, Juan Cinca, Carmen Tarifa, Leif Hove-Madsen
摘要

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). 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. 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.

材料
產品編號
品牌
產品描述

Sigma-Aldrich
Anti-Ryanodine Receptor Mouse mAb (C3-33), liquid, clone C3-33, Calbiochem®