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This work was supported by Spanish Ministry of Economy and Competitiveness (MINECO) Grants SAF2010-16044 and SAF2013-46663-R (to V.A.), SAF2011-30312 and SAF2014-58286-C2-1-R (to L.H.-M.), SAF2011-30088 (to E.D.), and SAF2014-52413-R (to C.L.-O.) and Fondo de Investigación Sanitaria del Instituto de Salud Carlos III Grants RD12/0042/0028 (to V.A.), RD12/0042/0011 (to J.T.), and RD12/0042/0002 (to L.H.-M.), with cofunding from the Fondo Europeo de Desarrollo Regional and the Progeria Research Foundation. J.A.G. is the recipient of a U-Mobility Grant from the Marie Curie cofunding of Regional, National and International Programme (Grant 246550). The Instituto Universitario de Oncología is supported by Obra Social Cajastur. The CNIC is supported by the MINECO and the Pro CNIC Foundation, and it is a Severo Ochoa Center of Excellence (MINECO Award SEV-2015-0505)., Rivera-Torres, J., Calvo, C.J., Llach, A., Guzmán-Martínez, G., Caballero, R., González-Gómez, C., Jiménez-Borreguero, L.J., Guadix, J.A., Osorio, F.G., López-Otín, C., Herraiz-Martínez, A., Cabello, N., Vallmitjana, A., Benítez, R., Gordon, L.B., Jalife, J., Pérez-Pomares, J.M., Tamargo, J., Delpón, E., Hove-Madsen, L., Filgueiras-Rama, D., Andrés, V.

© 2015, Springer-Verlag Berlin Heidelberg. Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p

The damaging effects of high plasma levels of cholesterol in the cardiovascular system are widely known, but little attention has been paid to direct effects on cardiomyocyte function. We therefore aimed at testing the hypothesis that Low Density Lipoprotein (LDL) cholesterol affects calcium dynamics and signal propagation in cultured atrial myocytes. For this purpose, mRNA and protein expression levels were determined by real time PCR and western blot analysis, respectively, and intracellular calcium was visualized in fluo-4 loaded atrial HL-1 myocyte cultures subjected to field stimulation. At low stimulation frequencies all cultures had uniform calcium transients at all tested LDL concentrations. However, 500 μg LDL/mL maximally reduced the calcium transient amplitude by 43% from 0.30±0.04 to 0.17±0.02 (p, This work was supported by grants from the Spanish Ministry of Science and Innovation: SAF2011-30312 and CNIC2009-08 to Leif Hove Madsen, DPI2009-06999 to Rau´ l Benı´tez and from the Spanish Ministry of Health and Consume: FIS PI11/00747 to Vicenta Llorente. Funding from Redes de Investigacio´n Cooperativa, Instituto de Salud Carlos III, red REDINSCOR RD06-0003-0000 and RD06-0003-0015 is also acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.