Modelling the electrophysiological endothelial cell response to bradykinin.
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.
Schuster
Alexander
A
Cellular Biophysics and Biomechanics Laboratory, Swiss Federal Institute of Technology, 1015, Lausanne, Switzerland. schuster@bioeng.ucsd.edu
Bény
Jean-Louis
JL
Meister
Jean-Jacques
JJ
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology*; D008955:Models, Cardiovascular; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013552:Swine
D015221:Potassium Channels; D001920:Bradykinin; D002118:Calcium