Cardiac Cell Hypertrophy In Vitro

Various conditions were used to investigate the importance of Ca 2+ signaling in triggering hypertrophy in neonatal rat cardiomyocytes in vitro . An increase in cell size and sarcomere reorganization were induced not only by treatment with receptor agonists, such as angiotensin II, aldosterone, and norepinephrine, but also by a small depolarization caused by an increase in the KCl concentration of the medium. This latter treatment has no direct effects on receptor signaling. All these hypertrophic treatments caused a long‐lasting increase in the frequency of spontaneous [Ca 2+ ] oscillations, causing nuclear translocation of transfected NFAT (GFP). Cyclosporine A inhibited hypertrophy and NFAT translocation, but not the increased oscillation frequency. We propose here that calcineurin–NFAT can act as integrators of the Ca 2+ signal and can decode alterations in the frequency even of very rapid Ca 2+ oscillations.