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 0.02 Hz), 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.