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Activation of the Liver Glycogen Phosphorylase by Ca2+Oscillations: a Theoretical Study

✍ Scribed by DAVID GALL; ERIKA BAUS; GENEVIÈVE DUPONT

Publisher
Elsevier Science
Year
2000
Tongue
English
Weight
185 KB
Volume
207
Category
Article
ISSN
0022-5193

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✦ Synopsis

Cytosolic calcium plays a crucial role as a second messenger in cellular signalling. Various cell types, including hepatocytes, display Ca> oscillations when stimulated by an extracellular signal. However, the biological relevance of this temporal organization remains unclear. In this paper, we investigate theoretically the e!ect of Ca> 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> concentration, we show that Ca> 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, speci"city can be encoded by the oscillation frequency. Finally, using a model for signal-induced Ca> oscillations based on Ca>-induced Ca> release, we show that realistic Ca> oscillations can potentiate the response to a hormonal stimulation. These results indicate that Ca> oscillations in hepatocytes could contribute to increase the e$ciency and speci"city of cellular signalling, as shown experimentally for gene expression in lymphocytes (Dolmetsch et al., 1998).

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