Roles of Na-transporter genes in disorders of electrolyte metabolism

我们使用培养的血管平滑肌细胞（VSMC）和肾细胞，以确定钠转运蛋白（钠泵，钠/氢交换器，和上皮钠通道）在盐平衡紊乱的作用。结果表明：1）VSMC、血清、高渗液（甘露醇和葡萄糖诱导）、皮质酮及其代谢产物11-脱氢皮质酮对Na泵α 1-和β1-mRNA表达、α-和β1-亚基蛋白表达和Na，K-ATP酶活性的刺激差异内源性醛固酮水平升高可增加大鼠肾脏髓质上皮细胞Na通道α亚单位mRNA水平，但对β或γ亚单位mRNA水平无影响; 3）在兔皮质集合管（CCD）中，基底外侧钾浓度从2.5 mM急剧升高至8.5 mM激活了基底外侧钠泵，从而继发性地升高了顶端Na和K电导。DOCA预处理增加了基底外侧钾电导，并增强了基底外侧钠泵活性和顶端阳离子电导对钾升高的反应。腔钠浓度，可能是通过细胞钠浓度的变化，调制基底外侧钠泵和顶端阳离子电导之间的紧密耦合; 4）在对照兔的CCD中，将腔钠浓度从14 mM提高到147 mM，通过增加细胞钠浓度激活基底外侧钠泵和顶端Na和K电导。在DOCA处理的兔CCD中，基底外侧泵和顶端阳离子电导的腔Na依赖性激活急剧增强。慢性DOCA预处理也增加了基底外侧K电导后，提高管腔Na浓度; 5）在VSMC中，醛固酮激活Na/H交换（NHE）的非基因组和基因组机制; 6）低K培养基中孵育的OKP细胞增加NHE 3活性后，早期降低细胞内PH值;和7）细胞外氯调制收缩诱导的激活NHE在大鼠肾系膜细胞。

We used cultured vascular smooth muscle cells (VSMC) and kidney cells to determine the roles of Na-transporters (Na pump, Na/H exchanger, and epithelial Na channel) in the disorders of salt balance. The results were in the following:1) In VSMC, serum, hyperosmolality (induced by mannitol and glucose), corticosterone and its metabolite, 11-dehydrocorticosterone, differentially stimulated Na pump αl-and β1-mRNA expression, α- and β1-subunit protein expression, and Na, K-ATPase activity; 2) Low Na diet (elevated endogenous aldosterone levels) increased epithelial Na channel α subunit mRNA levels from inner medulla of the rat kidneys, but did not affect β or γ subunit mRNA levels; 3) In the rabbit cortical collecting duct (CCD), acute elevation of basolateral K concentrations from 2.5 to 8.5 mM activated the basolateral Na pump, which secondarily elevates the apical Na and K conductances. DOCA pretreatment increased the basolateral K conductances and augmented the response to the rise of K of both the basolateral Na pump activity and the apical cation conductances. Luminal Na concentration, probably by changes in cell Na concentrations, modulated the tight coupling between the basolateral Na pump and apical cation conductances; 4) In the CCD from control rabbits, raising luminal Na concentrations from 14 to 147 mM activated basolateral Na pump and apical Na and K conductances via increased cell Na concentration. The luminal Na-dependent activation of the basolateral pump and the apical cation conductances was sharply enhanced in the CCD from DOCA-treated rabbits. Chronic DOCA pretreatment also increased basolateral K conductance upon raising luminal Na concentration; 5) In VSMC, aldosterone activated Na/H exchange (NHE) by nongenomic and genomic mechanisms; 6) Incubation of OKP cells in low-K media increased NHE3 activity after early decrease in intracellular PH; and 7) Extracellular Cl modulated shrinkage-induced activation of NHE in rat renal mesangial cells.