Cardiac FGF23 Increases Intracellular Calcium in Atrial Myocytes and the Susceptibility to Atrial Fibrillation Decreased in FGF23f / fMyHCCre /+ Mice.

Exogenous fibroblast growth factor (FGF) 23 is closely associated with atrial fibrillation (AF) and is able to alter the cardiac electrophysiological activity by increasing intracellular calcium. While its arrhythmogenic mechanism remains unclear, this study aims to investigate the electrophysiological effects of cardiac FGF23 on intracellular calcium in atrial cells and its underlying mechanism. The incidence of AF was significantly decreased in FGF23f/fMyHCCre/+ mice compared to Cre mice. A significant increase in the incidence of triggering activity (TA), L-type calcium currents (ICa,L) and systolic calcium transient was induced in neonatal mice atrial myocytes (NMAMs) from the overexpression of FGF23. Conversely, the opposite effects were exhibited as a reduced diastolic spontaneous calcium leak and weakened Na+/Ca2+ exchange (NCX) function in cardiac myocytes from FGF23f/fMyHCCre/+ mice, which can reduce incidences of AF induced by delayed after depolarization (DAD). In addition, ryanodine-receptor 2 (RyR2) of calcium regulatory proteins was significantly downregulated in FGF23f/fMyHCCre/+ mice and upregulated in FGF23 overexpression of NMAMs. In conclusion, overexpression of cardiac FGF23 may increase the susceptibility to AF due to DAD or TA induced by increasing intracellular calcium in atrial myocytes.