Dynamic modeling for flow-activated chloride-selective membrane current in vascular endothelial cells

Abstract

In this paper, a dynamic model is proposed to quantify the relationship between fluid flow and Cl-- selective membrane current in vascular endothelial cells (VECs). It is assumed that the external shear stress would first induce channel deformation in VECs. This deformation could activate the Cl- channels on the membrane, thus allowing Cl- transport across the membrane. A modified Hodgkin- Huxley model is embedded into our dynamic system to describe the electrophysiological properties of the membrane, such as the Cl--selective membrane current (I ), voltage (V) and conductance. Three flow patterns, i. e., steady flow, oscillatory flow, and pulsatile flow, are applied in our simulation studies. When the extracellular Cl- concentration is constant, the I -V characteristics predicted by our dynamic model shows strong consistency with the experimental observations. It is also interesting to note that the Cl- currents under different flow patterns show some differences, indicating that VECs distinguish among and respond differently to different types of flows. When the extracellular Cl - concentration keeps constant or varies slowly with time (i.e. oscillates at 0.02Hz), the convection and diffusion of Cl- in extracellular space can be ignored and the Cl- current is well captured by the modified Hodgkin-Huxley model alone. However, when the extracellular Cl- varies fast (i.e., oscillates at 0.2 Hz), the convection and diffusion effect should be considered because the Cl- current dynamics is different from the case where the convection-diffusion effect is simply ignored. The proposed dynamic model along with the simulation results could not only provide more insights into the flow-regulated electrophysiological behavior of the cell membrane but also help to reveal new findings in the electrophysiological experimental investigations of VECs in response to dynamic flow and biochemical stimuli. © Springer-Verlag 2010.