Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney.
Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney.
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K( )-Cl(-) 协同转运蛋白在肾脏中发挥作用的分子证据。
DOI：
10.1152/ajprenal.00390.2013
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Gamba,Gerardo
中科院分区：
文献类型：
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作者：
Melo,Zesergio;Cruz-Rangel,Silvia;Bautista,Rocio;Vazquez,Norma;Castaneda-Bueno,Maria;Mount,DavidB;Pasantes-Morales,Herminia;Mercado,Adriana;Gamba,Gerardo
K+-ClKCC亚型3(KCC3)和4(KCC4)表达于近曲小管细胞的基底外侧膜，KCC4表达于Henle‘s肢厚升环的基底外侧膜和集合管的α嵌插细胞。然而，人们对这些转运蛋白在肾脏中的生理作用知之甚少。我们研究了5种实验条件下雄性Wistar大鼠或C57小鼠KCC3和KCC4的基因和蛋白表达水平及肾内分布：单剂量链脲佐菌素引起的高血糖、低盐饮食、饮用水中氯化铵引起的代谢性酸中毒以及低K+或高K+饮食。KCC3mRNA和蛋白在高血糖时肾皮质和近端小管细胞基侧膜上表达增加，但在低盐饮食或酸中毒时不表达。相反，低钠饮食在整个肾脏和肾外髓质代谢性酸中毒，特别是在α嵌入细胞的基侧膜上，KCC4蛋白的表达增加。在WNK4基因敲除小鼠中，也观察到低盐饮食增加了KCC4的蛋白表达，这表明在这种情况下KCC4的上调不是WNK4依赖的。KCC3和KCC4蛋白在低K+和高K+饮食下的表达没有变化。我们的数据与KCC3在近端小管葡萄糖重吸收机制中的作用以及KCC4在Henle‘s环粗大上升环的盐重吸收和集合管的酸分泌中的作用是一致的。
K+-Cl−cotransporter (KCC) isoforms 3 (KCC3) and 4 (KCC4) are expressed at the basolateral membrane of proximal convoluted tubule cells, and KCC4 is present in the basolateral membrane of the thick ascending loop of Henle's limb and α-intercalated cells of the collecting duct. Little is known, however, about the physiological roles of these transporters in the kidney. We evaluated KCC3 and KCC4 mRNA and protein expression levels and intrarenal distribution in male Wistar rats or C57 mice under five experimental conditions: hyperglycemia after a single dose of streptozotocin, a low-salt diet, metabolic acidosis induced by ammonium chloride in drinking water, and low- or high-K+diets. Both KCC3 mRNA and protein expression were increased during hyperglycemia in the renal cortex and at the basolateral membrane of proximal tubule cells but not with a low-salt diet or acidosis. In contrast, KCC4 protein expression was increased by a low-sodium diet in the whole kidney and by metabolic acidosis in the renal outer medulla, specifically at the basolateral membrane of α-intercalated cells. The increased protein expression of KCC4 by a low-salt diet was also observed in WNK4 knockout mice, suggesting that upregulation of KCC4 in these circumstances is not WNK4 dependent. No change in KCC3 or KCC4 protein expression was observed under low- or high-K+diets. Our data are consistent with a role for KCC3 in the proximal tubule glucose reabsorption mechanism and for KCC4 in salt reabsorption of the thick ascending loop of Henle's loop and acid secretion of the collecting duct.