Influence of sex on intracellular calcium homoeostasis in patients with atrial fibrillation.
Afterdepolarizations
Calcium sparks
Ryanodine receptor phosphorylation
Sarcoplasmic reticulum calcium release
Transient inward current
Journal
Cardiovascular research
ISSN: 1755-3245
Titre abrégé: Cardiovasc Res
Pays: England
ID NLM: 0077427
Informations de publication
Date de publication:
16 03 2022
16 03 2022
Historique:
received:
21
10
2020
accepted:
30
03
2021
pubmed:
1
4
2021
medline:
26
4
2022
entrez:
31
3
2021
Statut:
ppublish
Résumé
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 (ICa) 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 (ITi) 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/µm2) 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 ITIs and afterdepolarizations. This was linked to higher ryanodine receptor phosphorylation at s2808 in women with AF, and inhibition of adenosine A2A or beta-adrenergic receptors that modulate s2808 phosphorylation was able to reduce the higher incidence of ITI 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 ICa density in men only.
Identifiants
pubmed: 33788918
pii: 6206778
doi: 10.1093/cvr/cvab127
pmc: PMC8930070
doi:
Substances chimiques
Ryanodine Receptor Calcium Release Channel
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1033-1045Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
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