Expression and Impact of Adenosine A3 Receptors on Calcium Homeostasis in Human Right Atrium
Increased adenosine A receptor (AR) expression and activation underlies a higher incidence of spontaneous calcium release in atrial fibrillation (AF). Adenosine A receptors (AR) could counteract excessive AR activation, but their functional role in the atrium remains elusive, and we therefore aimed...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:302804 |
| Acceso en línea: | https://ddd.uab.cat/record/302804 https://dx.doi.org/urn:doi:10.3390/ijms24054404 |
| Access Level: | acceso abierto |
| Palabra clave: | L-type calcium current Adenosine A2A receptor Adenosine A3 receptor Calcium spark Electrophysiology Human atrial myocyte Sarcoplasmic reticulum Transient inward current |
| Sumario: | Increased adenosine A receptor (AR) expression and activation underlies a higher incidence of spontaneous calcium release in atrial fibrillation (AF). Adenosine A receptors (AR) could counteract excessive AR activation, but their functional role in the atrium remains elusive, and we therefore aimed to address the impact of ARs 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. AR mRNA accounted for 9% and AR mRNA for 32%. At baseline, AR inhibition increased the transient inward current (I) frequency from 0.28 to 0.81 events/min (p < 0.05). Simultaneous stimulation of ARs and ARs increased the calcium spark frequency seven-fold (p < 0.001) and the I frequency from 0.14 to 0.64 events/min (p < 0.05). Subsequent AR inhibition caused a strong additional increase in the I 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, ARs are expressed and blunt spontaneous calcium release at baseline and upon AR-stimulation in human atrial myocytes, pointing to AR activation as a means to attenuate physiological and pathological elevations of spontaneous calcium release events. |
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