Expression and Impact of Adenosine A(3) Receptors on Calcium Homeostasis in Human Right Atrium
Por:
Tarifa, C, Jimenez-Sabado, V, Franco, R, Montiel, J, Guerra, J, Ciruela, F, Hove-Madsen, L
Publicada:
1 mar 2023
Ahead of Print:
23 feb 2023
Resumen:
Increased adenosine A(2A) receptor (A(2A)R) expression and activation underlies a higher incidence of spontaneous calcium release in atrial fibrillation (AF). Adenosine A(3) receptors (A(3)R) could counteract excessive A(2A)R activation, but their functional role in the atrium remains elusive, and we therefore aimed to address the impact of A(3)Rs on intracellular calcium homeostasis. For this purpose, we analyzed right atrial samples or myocytes from 53 patients without AF, using quantitative PCR, patch-clamp technique, immunofluorescent labeling or confocal calcium imaging. A(3)R mRNA accounted for 9% and A(2A)R mRNA for 32%. At baseline, A(3)R inhibition increased the transient inward current (I-TI) frequency from 0.28 to 0.81 events/min (p < 0.05). Simultaneous stimulation of A(2A)Rs and A(3)Rs increased the calcium spark frequency seven-fold (p < 0.001) and the I-TI frequency from 0.14 to 0.64 events/min (p < 0.05). Subsequent A(3)R inhibition caused a strong additional increase in the I-TI frequency (to 2.04 events/min; p < 0.01) and increased phosphorylation at s2808 1.7-fold (p < 0.001). These pharmacological treatments had no significant effects on L-type calcium current density or sarcoplasmic reticulum calcium load. In conclusion, A(3)Rs are expressed and blunt spontaneous calcium release at baseline and upon A(2A)R-stimulation in human atrial myocytes, pointing to A(3)R activation as a means to attenuate physiological and pathological elevations of spontaneous calcium release events.
Filiaciones:
Tarifa, C:
IIBB CSIC, Biomed Res Inst Barcelona, Barcelona 08036, Spain
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08025, Spain
Jimenez-Sabado, V:
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Cardiol Dept, Barcelona 08025, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid 28029, Spain
Franco, R:
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona 08028, Spain
Montiel, J:
Hosp Santa Creu & Sant Pau, Cardiac Surg Dept, Barcelona 08025, Spain
Guerra, J:
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Cardiol Dept, Barcelona 08025, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid 28029, Spain
Ciruela, F:
Univ Barcelona, Inst Neurosci, Fac Med & Hlth Sci, Dept Pathol & Expt Therapeut,Pharmacol Unit, Lhospitalet De Llobregat 08907, Spain
IDIBELL, Inst Invest Biomed Bellvitge, Neurosci Program, Neuropharmacol & Pain Grp, Lhospitalet De Llobregat 08907, Spain
Hove-Madsen, L:
IIBB CSIC, Biomed Res Inst Barcelona, Barcelona 08036, Spain
Inst Invest Biomed St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Cardiol Dept, Barcelona 08025, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid 28029, Spain
gold, Green Published, All Open Access, Gold, Green
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