Cluzeaud F, Reyes R, Escoubet B, Fay M, Lazdunski M, Bonvalet J P, Lesage F, Farman N
Unité 478, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine X. Bichat, F-75870 Paris cedex 18, France.
Am J Physiol. 1998 Dec;275(6):C1602-9. doi: 10.1152/ajpcell.1998.275.6.C1602.
Several K+ conductances have been identified in the kidney, with specific properties and localization in distinct cell types and membrane domains. On the other hand, several K+ channels have been characterized at the molecular level. By immunolocalization, we show that a new inward rectifying K+ channel, TWIK-1, is specifically expressed in distinct tubular segments and cell types of the rat kidney. In the proximal tubule, TWIK-1 prevails in the initial portions (convoluted part), where it is restricted to the apical (brush-border) membrane. In the collecting duct, immunofluorescence was intracellular or confined to the apical membrane and restricted to intercalated cells, i.e., in cells lacking aquaporin-2, as shown by double immunofluorescence. TWIK was also expressed in medullary and cortical parts of the thick limb of the loop of Henle, identified with an anti-Tamm-Horsfall protein antibody (double immunofluorescence). The intensity of TWIK-1 immunolabeling was unchanged in rats fed a low-Na+ or a low-K+ diet. Because TWIK-1 shares common properties with the low-conductance apical K+ channel of the collecting duct, we propose that it could play a role in K+ secretion, complementary to ROMK, another recently characterized K+ channel located in principal cells of the cortical collecting duct and in the loop of Henle.
在肾脏中已鉴定出几种钾离子电导,它们在不同细胞类型和膜结构域中具有特定的特性和定位。另一方面,几种钾离子通道已在分子水平上得到表征。通过免疫定位,我们发现一种新的内向整流钾离子通道TWIK-1在大鼠肾脏的不同肾小管节段和细胞类型中特异性表达。在近端小管中,TWIK-1在起始部分(曲部)占主导,局限于顶端(刷状缘)膜。在集合管中,免疫荧光显示其位于细胞内或局限于顶端膜,且仅限于闰细胞,即缺乏水通道蛋白-2的细胞,双重免疫荧光显示了这一点。用抗Tamm-Horsfall蛋白抗体鉴定(双重免疫荧光),TWIK也在髓袢升支粗段的髓质和皮质部分表达。在低钠或低钾饮食喂养的大鼠中,TWIK-1免疫标记的强度没有变化。由于TWIK-1与集合管低电导顶端钾离子通道具有共同特性,我们认为它可能在钾离子分泌中发挥作用,与ROMK互补,ROMK是另一种最近在皮质集合管主细胞和髓袢中表征的钾离子通道。