Ca2+ signaling plays a central role in hypertrophic growth of cardiac and skeletal muscle in response to mechanical load and a variety of signals. However, the mechanisms whereby alterations in Ca2+ in the cytoplasm activate the hypertrophic response and result in longterm changes in muscle gene expression are unclear. The Ca2+, calmodulin-dependent protein phosphatase calcineurin has been proposed to control cardiac and skeletal muscle hypertrophy by acting as a Ca2+ sensor that couples prolonged changes in Ca2+ levels to reprogramming of muscle gene expression. Calcineurin also controls the contractile and metabolic properties of skeletal muscle by activating the slow muscle fiber-specific gene program, which is dependent on Ca2+ signaling. Transcription factors of the NFAT and MEF2 families serve as endpoints for the signaling pathways whereby calcineurin controls muscle hypertrophy and fiber-type. We consider these findings in the context of a model for Ca2+-regulated gene expression in muscle cells and discuss potential implications of these findings for pharmacologic modification of cardiac and skeletal muscle function. (C) 2000 John Wiley and Sons, Inc.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Jan 1 2000|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)