Influence of sex on intracellular calcium homoeostasis in patients with atrial fibrillation
Por:
Herraiz-Martinez, A, Tarifa, C, Jimenez-Sabado, V, Llach, A, Godoy-Marin, H, Colino, H, Nolla-Colomer, C, Casabella, S, Izquierdo-Castro, P, Benitez, I, Benitez, R, Rosello-Diez, E, Rodriguez-Font, E, Vinolas, X, Ciruela, F, Cinca, J, Hove-Madsen, L
Publicada:
16 mar 2022
Ahead of Print:
1 may 2021
Resumen:
Aims 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. Methods and results 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-Ca) 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-Ti) 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/mu m(2)) and sparks were wider (3.0 +/- 0.3 vs. 2.2 +/- 0.3 mu m) and lasted longer (79 +/- 6 vs. 55 +/- 8 ms), favouring their fusion into calcium waves that triggers I(TI)s and afterdepolarizations. This was linked to higher ryanodine receptor phosphorylation at s2808 in women with AF, and inhibition of adenosine A(2A) or beta-adrenergic receptors that modulate s2808 phosphorylation was able to reduce the higher incidence of I-TI in women with AF. Conclusion 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-Ca density in men only.
Filiaciones:
Herraiz-Martinez, A:
CSIC, Dept Expt Pathol, Biomed Res Inst Barcelona IIBB, Rossello 161, Barcelona 08036, Spain
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Tarifa, C:
CSIC, Dept Expt Pathol, Biomed Res Inst Barcelona IIBB, Rossello 161, Barcelona 08036, Spain
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Jimenez-Sabado, V:
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Inst Salud Carlos III, CIBERCV, Pabellon 11,Monforte de Lemos 3-5, Madrid 28029, Spain
Llach, A:
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Godoy-Marin, H:
Univ Barcelona, Neurosci Program, IDIBEL, Neuropharmacol & Pain Grp, Avinguda Granvia Hosp 199, Barcelona 08908, Spain
Univ Barcelona, Neurosci Inst, Dept Pathol & Expt Therapeut, Campus Mundet Pg Vall dHebron 171, Barcelona 08035, Spain
Colino, H:
CSIC, Dept Expt Pathol, Biomed Res Inst Barcelona IIBB, Rossello 161, Barcelona 08036, Spain
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Nolla-Colomer, C:
Univ Politecn Cataluna, Dept Automat Control, Campus Diagonal Sud,Bldg H,Av Diagonal 647, Barcelona 08028, Spain
Casabella, S:
CSIC, Dept Expt Pathol, Biomed Res Inst Barcelona IIBB, Rossello 161, Barcelona 08036, Spain
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Izquierdo-Castro, P:
CSIC, Dept Expt Pathol, Biomed Res Inst Barcelona IIBB, Rossello 161, Barcelona 08036, Spain
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Benitez, I:
IRBLleida, Biostat Unit, Translat Res Resp Med, Biomed Res Inst, Av Alcalde Rovira Roure 80, Lleida 25198, Spain
Benitez, R:
Univ Politecn Cataluna, Dept Automat Control, Campus Diagonal Sud,Bldg H,Av Diagonal 647, Barcelona 08028, Spain
Rosello-Diez, E:
Hosp Santa Creu & Sant Pau, Dept Cardiac Surg, St Antoni Ma Claret 167, Barcelona 08025, Spain
Univ Autonoma Barcelona, Fac Med, St Antoni Ma Claret 167, Barcelona 08025, Spain
Rodriguez-Font, E:
Hosp Santa Creu & Sant Pau, Dept Cardiol, St Antoni Ma Claret 167, Barcelona 08025, Spain
Vinolas, X:
Hosp Santa Creu & Sant Pau, Dept Cardiol, St Antoni Ma Claret 167, Barcelona 08025, Spain
Ciruela, F:
Univ Barcelona, Neurosci Program, IDIBEL, Neuropharmacol & Pain Grp, Avinguda Granvia Hosp 199, Barcelona 08908, Spain
Univ Barcelona, Neurosci Inst, Dept Pathol & Expt Therapeut, Campus Mundet Pg Vall dHebron 171, Barcelona 08035, Spain
Cinca, J:
Inst Salud Carlos III, CIBERCV, Pabellon 11,Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Fac Med, St Antoni Ma Claret 167, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Dept Cardiol, St Antoni Ma Claret 167, Barcelona 08025, Spain
Hove-Madsen, L:
CSIC, Dept Expt Pathol, Biomed Res Inst Barcelona IIBB, Rossello 161, Barcelona 08036, Spain
IIB St Pau, Dept Cardiovasc Dis, St Antoni Ma Claret 167, Barcelona 08025, Spain
Inst Salud Carlos III, CIBERCV, Pabellon 11,Monforte de Lemos 3-5, Madrid 28029, Spain
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