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

Area of Science:

• Biophysics
• Cellular Electrophysiology
• Fluid Dynamics

Background:

• Vascular endothelial cells (VECs) play a crucial role in regulating vascular tone and permeability.
• Fluid shear stress is known to influence VEC function, but the precise mechanisms of electrophysiological responses are not fully understood.
• Chloride (Cl(-)) channels are involved in various cellular processes, including membrane potential regulation.

Purpose of the Study:

• To develop and validate a dynamic model quantifying the relationship between fluid flow and Cl(-)-selective membrane current in VECs.
• To investigate how different flow patterns (steady, oscillatory, pulsatile) affect Cl(-) transport.
• To explore the role of extracellular Cl(-) concentration dynamics on membrane current.

Main Methods:

• A dynamic model integrating a modified Hodgkin-Huxley model was developed to simulate VEC electrophysiology.
• The model incorporates channel deformation induced by external shear stress.
• Simulations were performed under three distinct flow patterns with varying extracellular Cl(-) concentrations.

Main Results:

• The model accurately predicts I-V characteristics consistent with experimental data for constant extracellular Cl(-).
• Distinct flow patterns elicit different Cl(-) current responses, indicating VECs can differentiate flow types.
• Convection-diffusion effects of Cl(-) become significant at higher oscillation frequencies (0.2 Hz).

Conclusions:

• The proposed dynamic model provides insights into flow-regulated electrophysiological behavior of VECs.
• VECs exhibit distinct responses to different fluid flow patterns.
• The study highlights the importance of considering extracellular Cl(-) dynamics in VEC electrophysiology under varying flow conditions.