Calcium oscillations increase the efficiency and specificity of gene expression

Nature. 1998 Apr 30;392(6679):933-6. doi: 10.1038/31960.


Cytosolic calcium ([Ca2+]i) oscillations are a nearly universal mode of signalling in excitable and non-excitable cells. Although Ca2+ is known to mediate a diverse array of cell functions, it is not known whether oscillations contribute to the efficiency or specificity of signalling or are merely an inevitable consequence of the feedback control of [Ca2+]i. We have developed a Ca2+ clamp technique to investigate the roles of oscillation amplitude and frequency in regulating gene expression driven by the proinflammatory transcription factors NF-AT, Oct/OAP and NF-kappaB. Here we report that oscillations reduce the effective Ca2+ threshold for activating transcription factors, thereby increasing signal detection at low levels of stimulation. In addition, specificity is encoded by the oscillation frequency: rapid oscillations stimulate all three transcription factors, whereas infrequent oscillations activate only NF-kappaB. The genes encoding the cytokines interleukin (IL)-2 and IL-8 are also frequency-sensitive in a way that reflects their degree of dependence on NF-AT versus NF-kappaB. Our results provide direct evidence that [Ca2+]i oscillations increase both the efficacy and the information content of Ca2+ signals that lead to gene expression and cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Genes, Reporter
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-8 / genetics
  • Jurkat Cells
  • NF-kappa B / metabolism
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phosphorylation
  • Signal Transduction*
  • T-Lymphocytes / metabolism
  • Transcription Factors / metabolism*
  • Transfection


  • Calcium Channels
  • DNA-Binding Proteins
  • Interleukin-2
  • Interleukin-8
  • NF-kappa B
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • Calcium