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Sci. Signal., 24 June 2008
Vol. 1, Issue 25, p. pe31
[DOI: 10.1126/scisignal.125pe31]


Does Contractile Ca2+ Control Calcineurin-NFAT Signaling and Pathological Hypertrophy in Cardiac Myocytes?

Steven R. Houser1* and Jeffery D. Molkentin2*

1Department of Physiology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
2Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

Abstract: In noncontractile cells, a sustained increase in total cytoplasmic Ca2+ concentration is typically needed to activate the intracellular protein phosphatase calcineurin, leading to dephosphorylation of the transcription factor nuclear factor of activated T cells (NFAT), its nuclear translocation, and induction of gene expression. It remains a mystery exactly how Ca2+-dependent signaling pathways, such as that mediated by calcineurin-NFAT, are regulated in contracting cardiac myocytes given the highly specialized manner in which Ca2+ concentration rhythmically cycles in excitation-contraction coupling. Here, we critically review evidence that supports the hypothesis that calcineurin-NFAT signaling is regulated by contractile Ca2+ transients in cardiac myocytes.

*Corresponding authors. E-mail, srhouser{at} (S.R.H.); jeff.molkentin{at} (J.D.M.)

Citation: S. R. Houser, J. D. Molkentin, Does Contractile Ca2+ Control Calcineurin-NFAT Signaling and Pathological Hypertrophy in Cardiac Myocytes? Sci. Signal. 1, pe31 (2008).

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