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Página principal > Artículos > Artículos publicados > Impact of R-Carvedilol on β2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes |
Fecha: | 2022 |
Resumen: | A hallmark of atrial fibrillation is an excess of spontaneous calcium release events, which can be mimicked by β1- or β2-adrenergic stimulation. Because β1-adrenergic receptor blockers (β1-blockers) are primarily used in clinical practice, we here examined the impact of β2-adrenergic stimulation on spontaneous calcium release and assessed whether the R- and S-enantiomers of the non-selective β- blocker carvedilol could reverse these effects. For this purpose, human atrial myocytes were isolated from patients undergoing cardiovascular surgery and subjected to confocal calcium imaging or immunofluorescent labeling of the ryanodine receptor (RyR2). Interestingly, the β2-adrenergic agonist fenoterol increased the incidence of calcium sparks and waves to levels observed with the non-specific β-adrenergic agonist isoproterenol. Moreover, fenoterol increased both the amplitude and duration of the sparks, facilitating their fusion into calcium waves. Subsequent application of the non β-blocking R-Carvedilol enantiomer reversed these effects of fenoterol in a dose-dependent manner. R-Carvedilol also reversed the fenoterol-induced phosphorylation of the RyR2 at Ser-2808 dose-dependently, and 1 µM of either R- or S-Carvedilol fully reversed the effect of fenoterol. Together, these findings demonstrate that β2-adrenergic stimulation alone stimulates RyR2 phosphorylation at Ser-2808 and spontaneous calcium release maximally, and points to carvedilol as a tool to attenuate the pathological activation of β2-receptors. |
Ayudas: | Agencia Estatal de Investigación SAF2017-88019-C3-1-R Agencia Estatal de Investigación SAF2017-88019-C3-3-R Agencia Estatal de Investigación PID2020-116927RB-C21 Agencia Estatal de Investigación PID2020-116927RB-C22 Ministerio de Economía y Competitividad CB16/11/00276 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR2017-1769 |
Nota: | Altres ajuts: Fundació Marató TV3 (Marato2015-20-30, Marato2015-20-31); Canadian Institutes of Health Research (PJT-155940); Heart and Stroke Foundation of Canada (G-19-0026444); Heart and Stroke Foundation Chair in Cardiovascular Research (END611955). |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | β-adrenergic receptor blocker ; Human atrial myocyte ; Sarcoplasmic reticulum ; Calcium spark ; Arrhythmia ; Carvedilol |
Publicado en: | Biomedicines, Vol. 10 Núm. 7 (july 2022) , p. 1759, ISSN 2227-9059 |
13 p, 2.9 MB |