Cytosolic calcium plays a crucial role as a second messenger in cellular si
gnalling. Various cell types, including hepatocytes, display Ca2+ oscillati
ons when stimulated by an extracellular signal. However, the biological rel
evance of this temporal organization remains unclear. In this paper, we inv
estigate theoretically the effect of Ca2+ oscillations on a particular exam
ple of cell regulation: the phosphorylation-dephosphorylation cycle control
ling the activation of glycogen phosphorylase in hepatocytes. By modelling
periodic sinusoidal variations in the intracellular Ca2+ concentration, we
show that Ca2+ oscillations reduce the threshold for the activation of the
enzyme. Furthermore, as the activation of a given enzyme depends on the kin
etics of its phosphorylation-dephosphorylation cycle, specificity can be en
coded by the oscillation frequency. Finally, using a model for signal-induc
ed Ca2+ oscillations based on Ca2+-induced Ca2+ release, Lye show that real
istic Ca2+ oscillations can potentiate the response to a hormonal stimulati
on. These results indicate that Ca2+ oscillations in hepatocytes could cont
ribute to increase the efficiency and specificity of cellular signalling, a
s shown experimentally for gene expression in lymphocytes (Dolmetsch et al.
, 1998). (C) 2000 Academic Press.