Address for correspondence: Prof. Tullio Pozzan, Ph.D., Venetian Institute of Molecular Medicine, Department of Biomedical Sciences, via G. Colombo 3, 35129 Padua, Italy. Voice: +39 049 7923-231; fax: +39 049 7923-260. tullio.pozzan{at}unipd.it
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.
