TY - JOUR
T1 - Influence of sex on intracellular calcium homoeostasis in patients with atrial fibrillation
AU - Herraiz-Martínez, Adela
AU - Tarifa, Carmen
AU - Jiménez-Sábado, Verónica
AU - Llach, Anna
AU - Godoy-Marín, Hector
AU - Colino-Lage, Hildegard
AU - Nolla-Colomer, Carme
AU - Casabella Ramón, Sergi
AU - Izquierdo-Castro, Paloma
AU - Benítez, Iván
AU - Benítez, Raúl
AU - Roselló-Díez, Elena
AU - Rodríguez-Font, Enrique
AU - Viñolas, Xavier
AU - Ciruela, Francisco
AU - Cinca, Juan
AU - Hove-Madsen, Leif
PY - 2021
Y1 - 2021
N2 - 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 [
AB - 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 [
KW - Sarcoplasmic reticulum calcium release
KW - Calcium sparks
KW - Transient inward current
KW - Afterdepolarizations
KW - Ryanodine receptor phosphorylation
U2 - 10.1093/cvr/cvab127
DO - 10.1093/cvr/cvab127
M3 - Article
C2 - 33788918
SN - 0008-6363
VL - 118
SP - 1033
EP - 1045
JO - Cardiovascular Research
JF - Cardiovascular Research
ER -