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oxhamre

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A minimal generic model of bacteria-induced intracellular Ca2+ oscillations in epithelial cells.

  • Camilla Oxhamre
  • Agneta Richter-Dahlfors
  • Vladimir P Zhdanov
  • Bengt Kasemo
Biophys. J. 2005; 88 (4): 2976-2981
Abstract
The toxin alpha-hemolysin expressed by uropathogenic Escherichia coli bacteria was recently shown as the first pathophysiologically relevant protein to induce oscillations of the intracellular Ca(2+) concentration in target cells. Here, we propose a generic three-variable kinetic model describing the Ca(2+) oscillations induced in single rat renal epithelial cells by this toxin. Specifically, we take into account the interplay between 1), the cytosolic Ca(2+) concentration; 2), IP(3)-sensitive Ca(2+) channels located in the membrane separating the cytosol and endoplasmic reticulum; and 3), toxin-related activation of production of IP(3) by phospholipase C. With these ingredients, the predicted response of cells exposed to the toxin is in good agreement with the results of experiments.

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
1e-06 mole
60.0 second
Id Name Spatial dimensions Size
Cytosol 3.0 1.0
Endoplasmic_Reticulum 3.0 1.0
Id Name Initial quantity Compartment Fixed
CaER 0.0 Endoplasmic_Reticulum
Ca_Cyt 0.0 Cytosol
p3 p3 0.95 Cytosol

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
Jch Jch CaER > Ca_Cyt

Fch_0 * p1 * p2 * p3
Jleak Jleak CaER > Ca_Cyt

Fleak
Jpump Ca_Cyt > CaER

Fpump_0 * Ca_Cyt / (Kpump + Ca_Cyt)
p3_consumption p3_consumption p3 = ∅

k31 * Ca_Cyt * p3
p3_production p3_production ∅ = p3

k31 * K3 * (1 - p3)

Global parameters

Id Value
K1 5.0
K2 0.7
K3 0.7
k31 0.5
kappa 5.0
kbN 0.5
n 1.0
n0 1.0
p1 0.0
p11 0.2
p12 0.8
p2 0.0

Local parameters

Id Value Reaction
Fch_0 8.0 Jch (Jch)
Fleak 0.5 Jleak (Jleak)
Fpump_0 2.0 Jpump
Kpump 0.1 Jpump

Assignment rules

Definition
p2 = Ca_Cyt / (K2 + Ca_Cyt)
p1 = p11 + p12 * n / (K1 + n)
n = n0 * (exp(-kbN * time) + kappa * (1.0 - exp(-kbN * time)))

Rate rules

Definition

Algebraic rules

Definition
Trigger Assignments