Model Status
Made in COR. Model a runs in OpenCell to recreate results from published paper but model b does not reproduce results. CellML files are based on equations 1-3 (a) and 1 and 4-8 (b).
Model Structure
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).
The complete original paper reference is cited below:
Activation of the Liver Glycogen Phosphorylase by Ca2+ Oscillations: a Theoretical Study, David Gall et al, 2009, Activation of the Liver Glycogen Phosphorylase by Ca2+ Oscillations:
a Theoretical Study , 207, 445-454. PubMed ID: 11093832
Image depicting calcium flow in model
Calcium in cell
$\frac{d \mathrm{Pha}}{d \mathrm{time}}=\mathrm{V\_1}Z\frac{1-\mathrm{Pha}}{\mathrm{K\_1}Z+1-\mathrm{Pha}}-\frac{\mathrm{V\_M2}(1+\frac{\mathrm{alpha}\mathrm{Glc}}{\mathrm{K\_a1}+\mathrm{Glc}})\mathrm{Pha}}{\frac{\mathrm{K\_2}}{1+\frac{\mathrm{Glc}}{\mathrm{K\_a2}}}+\mathrm{Pha}}$
$\mathrm{V\_1}=\mathrm{V\_M1}(1+\mathrm{gamma}(\frac{Z^{4}}{\mathrm{K\_a5}^{4}}+Z^{4}))$
$\mathrm{K\_1}=\frac{\mathrm{K\_11}}{1+\frac{Z^{4}}{\mathrm{K\_a6}^{4}}}$
$\frac{d Z}{d \mathrm{time}}=\mathrm{V\_in}-\mathrm{V\_2i}+\mathrm{V\_3i}+\mathrm{k\_f}Y-kZ$
$\frac{d Y}{d \mathrm{time}}=\mathrm{V\_2i}-\mathrm{V\_3i}-\mathrm{k\_f}Y$
$\mathrm{V\_in}=\mathrm{v\_0}+\mathrm{v\_1}\mathrm{beta}$
$\mathrm{V\_2i}=\mathrm{v\_M2i}\frac{Z^{n}}{\mathrm{K\_2i}^{n}+Z^{n}}$
$\mathrm{V\_3i}=\mathrm{v\_M3i}(\frac{Y^{m}}{\mathrm{K\_Ri}^{m}}+Y^{n})\frac{Z^{p}}{\mathrm{K\_Ai}^{p}+Z^{p}}$
3
Nielsen
Hanne
hnie010@aucklanduni.ac.nz
The University of Auckland
Auckland Bioengineering Institute
2009-10-08
Human
Liver
hepatocyte
keyword
hepatology
liver
11093832
Gall
D
Baus
E
Dupont
G
Activation of the liver glycogen phosphorylase by Ca(2+)oscillations: a theoretical study
2009-07-08
Journal of Theoretical Biology
207(4)
445
454