Gee Michael T, Kurtz Ira, Pannabecker Thomas L
Department of Physiology, Banner-University Medical Center, University of Arizona, Tucson, AZ, 85724.
Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA.
Physiol Rep. 2019 May;7(10):e14089. doi: 10.14814/phy2.14089.
SLC4A11 is a multifunctional membrane transporter involved with H transport, NH and alkaline pH stimulated H transport, and water transport. The role of SLC4A11 in the kidney is not well understood. A prior study has shown that in murine kidney, SLC4A11/LacZ staining is primarily in the long-looped descending thin limb (DTL) as determined by colocalization with aquaporin 1 (AQP1), a protein that is expressed in some, but not all, descending thin limb segments. Using a previously characterized polyclonal antibody, we demonstrate the selective expression of SLC4A11 in the upper DTLs (which are AQP1-positive) in the outer medulla and inner medulla with little or no expression in the lower DTLs (which are AQP-1-null). SLC4A11 also colocalized with AQP1 and the urea transporter UT-B in the mouse descending vasa recta, but was absent in mouse and rat ascending vasa recta. Mouse, but not rat, outer medullary collecting duct cells also labeled for SLC4A11. Our results are compatible with the hypothesis that in the inner stripe of the outer medulla, SLC4A11 plays a role in the countercurrent transport of ammonia absorbed from the outer medullary thick ascending limb and secreted into the long-looped DTLs. SLC4A11 can potentially modulate the rate of ammonia transport in the mouse outer medullary collecting duct. Our data suggest functionally unique SLC4A11 pathways in mouse and rat and complement previous studies of DTL Na , urea and water permeability indicating that the upper and lower DTLs of long-looped nephrons are functionally distinct.
溶质载体家族4成员11(SLC4A11)是一种多功能膜转运蛋白,参与氢离子(H⁺)转运、铵离子(NH₄⁺)和碱性pH刺激的H⁺转运以及水转运。SLC4A11在肾脏中的作用尚未完全明确。先前的一项研究表明,在小鼠肾脏中,通过与水通道蛋白1(AQP1)共定位确定,SLC4A11/乳糖酶(LacZ)染色主要位于长襻降支细段(DTL),AQP1在部分而非全部降支细段表达。使用先前鉴定的多克隆抗体,我们证实SLC4A11在外髓质和内髓质的上DTL(AQP1阳性)中选择性表达,在下DTL(AQP-1阴性)中几乎不表达或无表达。SLC4A11在小鼠直小血管降支中也与AQP1和尿素转运蛋白UT-B共定位,但在小鼠和大鼠直小血管升支中不存在。小鼠外髓集合管细胞而非大鼠外髓集合管细胞也标记有SLC4A11。我们的结果与以下假设相符:在外髓质内带,SLC4A11在从外髓质厚升支吸收并分泌到长襻DTL的氨的逆流转运中发挥作用。SLC4A11可能调节小鼠外髓集合管中的氨转运速率。我们的数据表明小鼠和大鼠中SLC4A11的功能途径独特,补充了先前关于DTL钠、尿素和水通透性的研究,表明长襻肾单位的上、下DTL在功能上是不同的。