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 system. In vivo and in vitro, endothelial cells change their morphology and biochemistry in response to shear stress in a force- and time-dependent way, or when a critical threshold is exceeded. The initial stimulus-response coupling mechanisms have not been identified, however. Recently, Lansman et al. 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 nonselective 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 Ik.s) was identified which is unlike previously described stretch-activated currents. Ik.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. Ik.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 Ik.s may participate in the regulation of vascular tone.

Effects of Shear Stress on [Ca2+]I and Membrane Potential of Vascular Endothelium of Intact Rat Blood Vessels

“…Changes in endothelial cells in culture as discussed above may account for these differences, although species differences cannot be ruled out. Shear stress-activated hyperpolarisation has been reported in cultured endothelial cells (Nakache & Gaub, 1988;Olesen et al 1988;Jacobs et al 1995). In aortic strips, changes in the superfusion rate sufficient to evoke their relaxation did not affect membrane potential or the input resistance of the endothelium.…”

“…Cytosolic alkalinisation has been shown to activate NO synthesis (Fleming et al 1994). Shear stress has also been reported to evoke endothelial hyperpolarisation (Nakache & Gaub, 1988) via activation of a K¤ current (Olesen et al 1988). Hyperpolarisation might be transduced to vascular smooth muscle through myoendothelial gap junctions resulting in relaxation.…”

Mécanotransduction des forces hémodynamiques et organogenèse

“…Les CE possè-dent-elles un tel canal ionique? Il y a une quinzaine d'années, un courant potassique, spécifiquement activé en réponse aux forces de flux, a été détecté dans des CE en culture [23] (Figure 1). Il est fondamental de déterminer quel est le canal ionique responsable de ce courant et de tester sa sensibilité aux forces de flux.…”

Vascular Responses to Shear Stress: The Involvement of Mechanosensors in Endothelial Cells

“…Whole-cell patch-clamp recordings of single arterial endothelial cells exposed to controlled levels of laminar shear stress in capillary flow tubes demonstrated the evidence for a K + selective, shear stress-activated ionic current [41]. Treatment of endothelial cells with blocking agents to K + channel such as barium chloride or tetraethylammonium inhibited the induction of NO by shear stress and the induced expression of endothelial cell NO synthase (eNOS) and transforming growth factor beta-1 [43,44].…”

“…Earlier studies have shown that shear stress activates the inward-rectifying K + current leading to cell membrane hyperpolarization [41,42]. Whole-cell patch-clamp recordings of single arterial endothelial cells exposed to controlled levels of laminar shear stress in capillary flow tubes demonstrated the evidence for a K + selective, shear stress-activated ionic current [41].…”