Olesen S P, Clapham D E, Davies P F
Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Nature. 1988 Jan 14;331(6152):168-70. doi: 10.1038/331168a0.
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.
在整个血管系统中，血管内皮细胞层承受着多种由血液动力学产生的剪切应力。在体内和体外，内皮细胞会根据剪切应力，以力和时间依赖的方式，或在超过临界阈值时改变其形态和生化特性。然而，最初的刺激-反应偶联机制尚未明确。最近，兰斯曼等人描述了内皮细胞中的牵张激活离子通道，并认为它们可能参与对血流产生的机械力的反应。这些通道相对非选择性，通过抽吸诱导的膜拉伸而打开。在此，我们报告了在毛细管流动管中暴露于可控水平层流剪切应力的单个动脉内皮细胞的全细胞膜片钳记录。我们鉴定出一种钾离子选择性、剪切应力激活的离子电流（命名为Ik.s），它与先前描述的牵张激活电流不同。Ik.s的大小和持续时间随剪切应力而变化（在0.70达因/平方厘米时达到最大效应的一半），脱敏缓慢，在血流停止时迅速且完全恢复。Ik.s活性代表了迄今为止发现的血液动力对内皮细胞最早且最快的刺激-反应偶联。我们认为，涉及Ik.s的内皮局部血流激活超极化可能参与血管张力的调节。
