Ca 2+ oscillation frequency decoding in cardiac cell hypertrophy: Role of calcineurin/NFAT as Ca 2+ signal integrators
- 26 February 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (8), 2859-2864
- https://doi.org/10.1073/pnas.0712316105
Abstract
The role of Ca(2+) signaling in triggering hypertrophy was investigated in neonatal rat cardiomyocytes in vitro. We show that an increase in cell size and sarcomere reorganization were elicited by receptor agonists such as Angiotensin II, aldosterone, and norepinephrine and by a small rise in medium KCl concentration, a treatment devoid of direct effects on receptor functions. All these treatments increased the frequency of spontaneous [Ca(2+)] transients, caused nuclear translocation of transfected NFAT(GFP), and increased the expression of a NFAT-sensitive reporter gene. There was no increase in Ca(2+) spark frequency in the whole cell or in the perinuclear region under these conditions. Hypertrophy and NFAT translocation but not the increased frequency of [Ca(2+)] transients were inhibited by the calcineurin inhibitor cyclosporine A. Hypertrophy by the different stimuli was insensitive to inhibition of myofilament contraction. We concluded that calcineurin-NFAT can act as integrators of the contractile Ca(2+) signal, and that they can decode alterations in the frequency even of rapid Ca(2+) oscillations.This publication has 38 references indexed in Scilit:
- Remodelling Ca2+ signalling systems and cardiac hypertrophyBiochemical Society Transactions, 2006
- Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytesCardiovascular Research, 2005
- Histone Deacetylases 5 and 9 Govern Responsiveness of the Heart to a Subset of Stress Signals and Play Redundant Roles in Heart DevelopmentMolecular and Cellular Biology, 2004
- Calcium–calcineurin signaling in the regulation of cardiac hypertrophyBiochemical and Biophysical Research Communications, 2004
- Contractile arrest reveals calcium-dependent stimulation of SERCA2a mRNA expression in cultured ventricular cardiomyocytesCardiovascular Research, 2004
- Calcium signalling: dynamics, homeostasis and remodellingNature Reviews Molecular Cell Biology, 2003
- Cardiac Hypertrophy: The Good, the Bad, and the UglyAnnual Review of Physiology, 2003
- Aldosterone and the HeartTrends in Endocrinology & Metabolism, 2000
- Rapid shuttling of NF-AT in discrimination of Ca2+ signals and immunosuppressionNature, 1996
- Calcium Sparks: Elementary Events Underlying Excitation-Contraction Coupling in Heart MuscleScience, 1993