Home > Articles > Published articles > Influence of sex on intracellular calcium homoeostasis in patients with atrial fibrillation |
Date: | 2021 |
Abstract: | Atrial fibrillation (AF) has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue. Alterations in calcium regulatory mechanisms were assessed in human atrial myocytes from patients without AF or with long-standing persistent or permanent AF. Patch-clamp measurements revealed that L-type calcium current (I ) density was significantly smaller in males with than without AF (−1. 15 ± 0. 37 vs. −2. 06 ± 0. 29 pA/pF) but not in females with AF (−1. 88 ± 0. 40 vs. −2. 21 ± 0. 0. 30 pA/pF). In contrast, transient inward currents (I ) were more frequent in females with than without AF (1. 92 ± 0. 36 vs. 1. 10 ± 0. 19 events/min) but not in males with AF. Moreover, confocal calcium imaging showed that females with AF had more calcium spark sites than those without AF (9. 8 ± 1. 8 vs. 2. 2 ± 1. 9 sites/µm 2) and sparks were wider (3. 0 ± 0. 3 vs. 2. 2 ± 0. 3 µm) and lasted longer (79 ± 6 vs. 55 ± 8 ms), favouring their fusion into calcium waves that triggers I s and afterdepolarizations. This was linked to higher ryanodine receptor phosphorylation at s2808 in women with AF, and inhibition of adenosine A or beta-adrenergic receptors that modulate s2808 phosphorylation was able to reduce the higher incidence of I in women with AF. Perturbations of the calcium homoeostasis in AF is sex-dependent, concurring with increased spontaneous SR calcium release-induced electrical activity in women but not in men, and with diminished I density in men only. This work was supported by grants from The Spanish Ministry of Science Innovation and Universities [. |
Grants: | Instituto de Salud Carlos III PIE14/00034 Instituto de Salud Carlos III SBO-140028 Instituto de Salud Carlos III FPU/01250 Ministerio de Ciencia e Innovación SAF2017-88019-C3-1-R Ministerio de Ciencia e Innovación SAF2017-88019-C3-2-R Ministerio de Ciencia e Innovación SAF2017-87349-R Instituto de Salud Carlos III CB16/11/00276 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR/2017-1769 |
Note: | Altres ajuts: Fundació Marato TV3 [20152030/31]. |
Rights: | 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, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Subject: | Sarcoplasmic reticulum calcium release ; Calcium sparks ; Transient inward current ; Afterdepolarizations ; Ryanodine receptor phosphorylation |
Published in: | Cardiovascular research, Vol. 118 (march 2021) , p. 1033-1045, ISSN 1755-3245 |
13 p, 1.7 MB |