Köhler R, Distler A, Hoyer J
Department of Endocrinology and Nephrology, University Hospital Benjamin Franklin, Free University, Berlin, Germany.
J Hypertens. 1999 Mar;17(3):365-71. doi: 10.1097/00004872-199917030-00009.
To characterize and compare mechanosensitive cell currents in rat aortic endothelial cells from spontaneously hypertensive and Wistar-Kyoto rats.
By use of the patch-clamp technique, we investigated whole-cell currents of native rat aortic endothelial cells in the presence of mechanical stimulation elicited by hyposmotic cell swelling. In rat aortic endothelial cells, this hypotonic cell swelling induced a fourfold increase in outward-directed whole-cell currents carried by K+, leading to cell hyperpolarization and a small increase in inward-directed currents. Gadolinium, a blocker of stretch-activated cation channels, completely blocked hypotonic cell swelling-induced outward- and inward-directed whole-cell currents. Charybdotoxin, a blocker of Ca(2+)-dependent K+ channels, decreased hypotonic cell swelling-induced outward-directed currents by up to 85%. Disruption of actin filaments by cytochalasin B and of microtubuli by nocodazole reduced the activation of hypotonic cell swelling-induced whole-cell currents by 91 and 71%, respectively. In experimental hypertension, hypotonic cell swelling-induced whole-cell conductance was significantly increased in spontaneously hypertensive rats (331 +/- 20 pS/pF) compared with normotensive controls (167 +/- 7 pS/pF, P < 0.01), whereas basal and agonist-induced cell conductances were not altered.
Increased hypotonic swelling-induced currents in aortic endothelial cells from spontaneously hypertensive rats presumably reflect an increased density or mechanosensitivity of stretch-activated ion channels in experimental hypertension. The increased mechanosensitive whole-cell currents might indicate an altered endothelial mechanotransduction in experimental hypertension.
表征并比较自发性高血压大鼠和Wistar-Kyoto大鼠主动脉内皮细胞中的机械敏感细胞电流。
利用膜片钳技术，我们在低渗细胞肿胀引起的机械刺激存在的情况下，研究了天然大鼠主动脉内皮细胞的全细胞电流。在大鼠主动脉内皮细胞中，这种低渗细胞肿胀导致由K⁺携带的外向全细胞电流增加了四倍，导致细胞超极化以及内向电流的小幅增加。钆，一种拉伸激活阳离子通道阻滞剂，完全阻断了低渗细胞肿胀诱导的外向和内向全细胞电流。查尔霉素，一种Ca²⁺依赖性K⁺通道阻滞剂，使低渗细胞肿胀诱导的外向电流降低了高达85%。细胞松弛素B破坏肌动蛋白丝和诺考达唑破坏微管分别使低渗细胞肿胀诱导的全细胞电流激活降低了91%和71%。在实验性高血压中，与正常血压对照组（167±7 pS/pF，P<0.01）相比，自发性高血压大鼠中低渗细胞肿胀诱导的全细胞电导显著增加（331±20 pS/pF），而基础和激动剂诱导的细胞电导没有改变。
自发性高血压大鼠主动脉内皮细胞中低渗肿胀诱导电流的增加可能反映了实验性高血压中拉伸激活离子通道密度或机械敏感性的增加。机械敏感全细胞电流的增加可能表明实验性高血压中内皮机械转导发生了改变。
