Navarro García, José AlbertoFernández Velasco, MaríaVal Blasco, AlmudenaRodríguez Sánchez, ElenaAceves Ripoll, JenniferGómez-Hurtado, NievesSolís, JorgeBueno, HéctorRuilope Urioste, Luis MiguelRuiz Urtado, GemaEt al.2019-04-052019-04-052019Navarro-García, J. A., Delgado, C., Fernández-Velasco, M., Val-Blasco, A., Rodríguez-Sánchez, E., Aceves-Ripoll, J., ... & Praga, M. (2019). Fibroblast growth factor-23 promotes rhythm alterations and contractile dysfunction in adult ventricular cardiomyocytes. Nephrology Dialysis Transplantation, 34(11), 1864-1875. https://doi.org/10.1093/ndt/gfy3920931-05091460-2385http://hdl.handle.net/11268/7856BACKGROUND: Cardiac dysfunction and arrhythmia are common and onerous cardiovascular events in end-stage renal disease (ESRD) patients, especially those on dialysis. Fibroblast growth factor (FGF)-23 is a phosphate-regulating hormone whose levels dramatically increase as renal function declines. Beyond its role in phosphorus homeostasis, FGF-23 may elicit a direct effect on the heart. Whether FGF-23 modulates ventricular cardiac rhythm is unknown, prompting us to study its role on excitation-contraction (EC) coupling. METHODS: We examined FGF-23 in vitro actions on EC coupling in adult rat native ventricular cardiomyocytes using patch clamp and confocal microscopy and in vivo actions on cardiac rhythm using electrocardiogram. RESULTS: Compared with vehicle treatment, FGF-23 induced a significant decrease in rat cardiomyocyte contraction, L-type Ca2+ current, systolic Ca2+ transients and sarcoplasmic reticulum (SR) load and SR Ca2+-adenosine triphosphatase 2a pump activity. FGF-23 induced pro-arrhythmogenic activity in vitro and in vivo as automatic cardiomyocyte extracontractions and premature ventricular contractions. Diastolic spontaneous Ca2+ leak (sparks and waves) was significantly increased by FGF-23 via the calmodulin kinase type II (CaMKII)-dependent pathway related to hyperphosphorylation of ryanodine receptors at the CaMKII site Ser2814. Both contraction dysfunction and spontaneous pro-arrhythmic Ca2+ events induced by FGF-23 were blocked by soluble Klotho (sKlotho).engjournal article10.1093/ndt/gfy392restricted accessUrologíaCardiologíaSistema cardiovascular