Remodeling muscles with calcineurin

Bioessays. 2000 Jun;22(6):510-9. doi: 10.1002/(SICI)1521-1878(200006)22:6<510::AID-BIES4>3.0.CO;2-1.


Ca(2+) 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 Ca(2+) in the cytoplasm activate the hypertrophic response and result in longterm changes in muscle gene expression are unclear. The Ca(2+), calmodulin-dependent protein phosphatase calcineurin has been proposed to control cardiac and skeletal muscle hypertrophy by acting as a Ca(2+) sensor that couples prolonged changes in Ca(2+) 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 Ca(2+) 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 Ca(2+)-regulated gene expression in muscle cells and discuss potential implications of these findings for pharmacologic modification of cardiac and skeletal muscle function. BioEssays 22:510-519, 2000.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcineurin / physiology*
  • Calcium / metabolism
  • Cardiomegaly / etiology
  • Cardiomegaly / physiopathology
  • DNA-Binding Proteins / physiology
  • Gene Expression
  • Humans
  • Hypertrophy
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscles / pathology*
  • Muscles / physiopathology*
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Regeneration
  • Signal Transduction
  • Transcription Factors / physiology


  • DNA-Binding Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • Calcineurin
  • Calcium