Ion Channels in Endothelial Responses to Fluid Shear Stress

Abstract

Fluid shear stress is an important environmental cue that governs vascular physiology and pathology, but the molecular mechanisms that mediate endothelial responses to flow are only partially understood. Gating of ion channels by flow is one mechanism that may underlie many of the known responses. Here, we review the literature on endothelial ion channels whose activity is modulated by flow with an eye toward identifying important questions for future research.

FIGURE 1.

Diagram of putative shear stress-activated channel subtypes in endothelial cells and their interactions Specific candidate genes are listed below their subtype. Flow activates non-specific cation channels, which depolarize the cell and increase cytoplasmic calcium. Flow also activates voltage-gated and epithelial sodium channels (N_av and ENaC), which increase sodium influx, and calcium-sensitive chloride channels (CaCC), which increase chloride efflux. Activation of both of these channels leads to depolarization. Conversely, flow activates calcium-activated and inwardly rectifying potassium channels (K_ca and K_ir), leading to hyperpolarization. Calcium influx directly activates both CaCCs and K_ca channels. In contrast, hyperpolarization potentiates calcium influx through open channels by increasing the driving force, which propels calcium into the cell, whereas depolarization decreases this driving force. Additionally, depolarization directly activates voltage-gated channels like N_av,whereas hyperpolarization inhibits these channels.