Activation of the liver glycogen phosphorylase by Ca(2+)oscillations: a theoretical study.
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).
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Unité de Recherche sur le Cerveau (CP601), Faculté de Médecine, Université Libre de Bruxelles, Route de Lennik 808, Bruxelles, B-1070, Belgium.
Baus
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Dupont
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D000818:Animals; D020013:Calcium Signaling; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D008954:Models, Biological; D006005:Phosphorylases / Q000378:metabolism*
D006003:Glycogen; D006005:Phosphorylases; D005947:Glucose