Activation of the liver glycogen phosphorylase by Ca(2+)oscillations: a theoretical study

J Theor Biol. 2000 Dec 21;207(4):445-54. doi: 10.1006/jtbi.2000.2139.

Abstract

Cytosolic calcium plays a crucial role as a second messenger in cellular signalling. Various cell types, including hepatocytes, display Ca(2+)oscillations when stimulated by an extracellular signal. However, the biological relevance of this temporal organization remains unclear. In this paper, we investigate theoretically the effect of Ca(2+)oscillations on a particular example of cell regulation: the phosphorylation-dephosphorylation cycle controlling the activation of glycogen phosphorylase in hepatocytes. By modelling periodic sinusoidal variations in the intracellular Ca(2+)concentration, we show that Ca(2+)oscillations reduce the threshold for the activation of the enzyme. Furthermore, as the activation of a given enzyme depends on the kinetics of its phosphorylation-dephosphorylation cycle, specificity can be encoded by the oscillation frequency. Finally, using a model for signal-induced Ca(2+)oscillations based on Ca(2+)-induced Ca(2+)release, we show that realistic Ca(2+)oscillations can potentiate the response to a hormonal stimulation. These results indicate that Ca(2+)oscillations in hepatocytes could contribute to increase the efficiency and specificity of cellular signalling, as shown experimentally for gene expression in lymphocytes (Dolmetsch et al., 1998).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling*
  • Cytosol / metabolism
  • Enzyme Activation
  • Glucose / metabolism*
  • Glycogen / metabolism*
  • Hepatocytes / metabolism*
  • Models, Biological
  • Phosphorylases / metabolism*

Substances

  • Glycogen
  • Phosphorylases
  • Glucose