Modelling the electrophysiological endothelial cell response to bradykinin

Modelling the electrophysiological endothelial cell response to bradykinin

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

Schematic diagram of the model, describing the electrophysiological endothelial cell response to bradykinin.