Modelling the Electrophysiological Endothelial Cell Response to Bradykinin
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This CellML model runs in OpenCell and COR but does not relicate the published results. There are unit inconsistencies which need fixing. Also in the absence of published initial conditions/parameter values for Cai, IP3 and C, arbitary values were used. Further, there is no defining equation or paramter value for PoSKCa (the probability of the SK_Ca channel being open).
Model Structure
ABSTRACT: The goal of the present study is to construct a biophysical model of the coronary artery endothelial cell response to bradykinin. This model takes into account intracellular Ca2+ dynamics, membrane potential, a non-selective cation channel, and two Ca(2+)-dependent K+ channels, as well as intra- and extracellular Ca2+ sources. The model reproduces the experimental data available, and predicts certain quantities which would be hard to obtain experimentally, like the individual K+ channel currents when the membrane potential is allowed to freely evolve, the implication of epoxyeicosatrienoic acids (EETs), and the total K+ released during stimulation. The main results are: (1) the large-conductance K+ channel participates only very little in the overall response; (2) EETs are required in order to explain the experimental current-potential relationships, but are not an essential component of the bradykinin response; and (3) the total K+ released during stimulation gives rise to a concentration in the intercellular space which is of millimolar order. This concentration change is compatible with the hypothesis that K+ contributes to the endothelium-derived hyperpolarizing factor phenomenon.
The original paper reference is cited below:
Modelling the electrophysiological endothelial cell response to bradykinin, Alexander Schuster, Jean-Louis Beny, and Jean-Jacques Meister, 2003, European Biophysics Journal, 32, 370-380. PubMed ID: 12851795
cell diagram
Schematic diagram of the model, describing the electrophysiological endothelial cell response to bradykinin.
$\frac{d \mathrm{Vm}}{d \mathrm{time}}=-\left(\frac{1.0}{C}\right)(\mathrm{i\_K}+\mathrm{i\_R})$
$\frac{d \mathrm{IP3}}{d \mathrm{time}}=A(1.0+\tanh \left(\frac{\mathrm{m3IP3}-\mathrm{time}}{\mathrm{m4IP3}}\right))-\mathrm{kIP3}\mathrm{IP3}$
$\frac{d \mathrm{Ca}}{d \mathrm{time}}=\frac{\mathrm{kSR\_rel}}{2.0}(1.0+\tanh \left(\frac{\mathrm{IP3}-\mathrm{m3SR}}{\mathrm{m4SR}}\right))-\frac{\mathrm{kPMCA}}{2.0}(1.0+\tanh \left(\frac{\lg \mathrm{Ca}-\mathrm{m3PMCA}}{\mathrm{m4PMCA}}\right))$
$\mathrm{Jcat}=\mathrm{Gcat}(\mathrm{ECa}-\mathrm{Vm})0.5(1.0+\tanh \left(\frac{\lg \mathrm{Ca}-\mathrm{m3cat}}{\mathrm{m4cat}}\right))$
$\mathrm{i\_K}=\mathrm{Gtot}(\mathrm{Vm}-\mathrm{E\_K})(0.4\mathrm{PoBKCa}+0.6\mathrm{PoSKCa})\mathrm{PoBKCa}=0.5(1.0+\tanh \left(\frac{(\lg \mathrm{Ca}-c)(\mathrm{Vm}-b)-a}{\mathrm{m3}(\mathrm{Vm}+a(\lg \mathrm{Ca}-c)-b)^{2.0}+\mathrm{m4}}\right))$
$\mathrm{i\_R}=\mathrm{GR}(\mathrm{Vm}-\mathrm{Vrest})$
endothelial cell
bradykinin
pharmacology
signal transduction
electrophysiology
endothelial cell
cardiac
keyword
The University of Auckland
Auckland Bioengineering Institute
Catherine Lloyd
This is the CellML description of Schuster et al.'s 2003 mathematical model of the electrophysiological endothelial cell response to bradykinin.
Modelling the electrophysiological endothelial cell response to bradykinin
32
370
380
The University of Auckland, Auckland Bioengineering Institute
Jean-Louis
Beny
2003-07
Catherine
Lloyd
May
Schuster et al.'s 2003 mathematical model of the electrophysiological endothelial cell response to bradykinin.
endothelial cell
12851795
2004-01-20
Alexander
Schuster
European Biophysical Journal
Jean-Jacques
Meister
c.lloyd@auckland.ac.nz