Max-Planck-Institut für Herz- und Lungenforschung, Parkstrasse 1, D-61231 Bad Nauheim, Germany.
J Biol Chem. 2010 May 7;285(19):14467-74. doi: 10.1074/jbc.M109.094680. Epub 2010 Feb 25.
Maintenance of ion concentration gradients is essential for the function of many organs, including the kidney, the cornea, and the inner ear. Ion concentrations and fluid content in the cornea are regulated by endothelial cells that separate the collagenous avascular corneal stroma from the anterior eye chamber. Failure to maintain correct ion concentrations leads to swelling and destruction of the cornea. In the inner ear, the stria vascularis is responsible for generating proper ion concentrations in the endolymph, which is essential for hearing. Mutations of SLC4A11 in humans lead to syndromes associated with corneal dystrophy and perceptive deafness. The molecular mechanisms underlying these symptoms are poorly understood, impeding therapeutic interventions. The ion transporter SLC4A11 mediates sodium-dependent transport of borate as well as flux of sodium and hydroxyl ions in vitro. Here, we show that SLC4A11 is expressed in the endothelial cells of the cornea where it prevents severe morphological changes of the cornea caused by increased sodium chloride concentrations in the stroma. In the inner ear, SLC4A11 is located in fibrocytes underlying the stria vascularis. Loss of SLC4A11 leads to morphological changes in the fibrocytes and deafness. We demonstrate that SLC4A11 is essential for the generation of the endocochlear potential but not for regulation of potassium concentrations in the endolymph. In the kidney, SLC4A11 is expressed in the thin descending limb of Henle loop. SLC4A11 is essential for urinary concentration, suggesting that SLC4A11 participates in the countercurrent multiplication that concentrates urine in the kidney medulla.
维持离子浓度梯度对于许多器官的功能至关重要，包括肾脏、角膜和内耳。角膜中的离子浓度和液体含量由内皮细胞调节，这些细胞将富含胶原蛋白的无血管角膜基质与前房分开。离子浓度不能维持在正确水平会导致角膜肿胀和破坏。在内耳中，血管纹负责在内淋巴中产生适当的离子浓度，这对听力至关重要。人类 SLC4A11 的突变导致与角膜营养不良和感觉性耳聋相关的综合征。这些症状的分子机制尚不清楚，阻碍了治疗干预。离子转运蛋白 SLC4A11 介导硼酸盐的钠依赖性转运以及体外钠离子和氢氧根离子的通量。在这里，我们表明 SLC4A11 在角膜的内皮细胞中表达，它可以防止基质中氯化钠浓度增加引起的角膜严重形态变化。在内耳中，SLC4A11 位于血管纹下方的纤维细胞中。SLC4A11 的缺失会导致纤维细胞的形态变化和耳聋。我们证明 SLC4A11 对于内淋巴中钾离子浓度的调节是必需的，但对于内耳电位的产生是必需的。在肾脏中，SLC4A11 在 Henle 袢的降支中表达。SLC4A11 对于尿液浓缩是必需的，这表明 SLC4A11 参与了在肾脏髓质中浓缩尿液的逆流倍增。
