Haemodynamic shear stress activates a K⁺ current in vascular endothelial cells

Abstract

The endothelial lining of blood vessels is subjected to a wide range of haemodynamically-generated shear-stress forces throughout the vascular system¹. In vivo and in vitro, endothelial cells change their morphology^2,3 and biochemistry⁴ in response to shear stress in a force- and time-dependent way, or when a critical threshold is exceeded^5'6. The initial stimulus–response coupling mechanisms have not been identified, however. Recently, Lansman et al.⁷ described stretch-activated ion channels in endothelial cells and suggested that they could be involved in the response to mechanical forces generated by blood flow. The channels were relatively non-selective and were opened by membrane stretching induced by suction. Here we report whole-cell patch-clamp recordings of single arterial endothelial cells exposed to controlled levels of laminar shear stress in capillary flow tubes. A K⁺ selective, shear-stress-activated ionic current (designated I_K.s) was identified which is unlike previously described stretch-activated currents. I^K.s varies in magnitude and duration as a function of shear stress (half-maximal effect at 0.70 dyn cm⁻²), desensitizes slowly and recovers rapidly and fully on cessation of flow. I^K.s activity represents the earliest and fastest stimulus–response coupling of haemodynamic forces to endothelial cells yet found. We suggest that localized flow-activated hyperpolarization of endothelium involving I^K.s may participate in the regulation of vascular tone.