Na-K-Cl协同转运蛋白研究进展

Advances of Na-K-Cl Cotransporter

Na-K-Cl协同转运蛋白是一类膜蛋白,负责转运Na、K、Cl离子进出上皮细胞与非上皮细胞。Na-K-Cl介导的转运过程是电中性的,多数情况下是1Na:1K:2Cl(乌贼轴突中是2Na:1 K:3Cl),其活性被布美他尼(bumetanide)和呋塞米(furosemide)所抑制。迄今为止,Na-K-Cl协同转运蛋白被鉴定出来两个同源异构体:NKCC1和NKCC2。NKCC1存在于多个组织中,含有NKCC1的上皮大多数属于分泌上皮,而且会有Na-K-Cl协同转运蛋白位于基底膜外侧;NKCC2只存在于肾脏,位于上皮细胞致密班的顶膜上。Na-K-Cl协同转运蛋白的调控在不同的细胞和组织中是不同的。Na-K-Cl协同转运蛋白的活性会受激素刺激和细胞体积变化的影响;有些组织中,这种调控作用(尤其是NKCC1亚基)是通过特定的激酶使该转运蛋白自身发生氧化/硝化、磷酸化/去磷酸化来实现的;蛋白过表达在Na-K-Cl协同转运蛋白的激活中也起重要作用。

The Na-K-Cl cotransporters are a class of membrane proteins that transport Na, K, and Cl ions into and out of a wide variety of epithelial and nonepithelial cells.The transport process mediated by Na-K-Cl cotransporters is characterized by electrically neutral stoichiometries of 1 Na：l K：2 Cl （for most cells） and 2 Na：l K：3 Cl （in squid axon） and inhibition by the ＂loop＂ diuretics bumetanide and furosemide. So far, two distinct Na-K-Cl cotransporter isoforms have been identified, named NKCC1 and NKCC2. The NKCC1 isoform is present in a wide variety of tissues, most epithelia containing NKCCl are secretory epithelia with the Na-K-Cl cotransporter localized to the basolateral membrane; NKCC2 is found only in the kidney, localized to the apical membrane of the epithelial cells of the thick ascending limb. The regulation of Na-K-Cl cotransport is extremely diverse, and varies greatly among different cells and tissues. Na-K-Cl cotransporter activity is affected by a large variety of hormonal stimuli as well as by changes in cell volume; in many tissues this regulation （particularly of the NKCCl isoform） occurs through direct oxidative/nitrosative, phosphorylation/dephosphorylation of the cotransport protein itself through the specific protein kinases. Increased NKCC 1 protein expression was recently shown to contribute to its increased activity.