CONTROL OF EPITHELIAL NA+ TRANSPORT BY APICAL NA+ ENTRY

在肾上皮细胞中，载体钠转运是一个分两步进行的过程。 首先，钠离子进入阿米洛利可阻断的离子通道。 位于钠转运细胞的顶膜。第二, 钠通过基底侧向外主动运输出细胞。 Na/K-ATPase。这两个过程的净影响是 一连串的，是钠从管腔的矢量传输 舱室到底侧舱室。之前的数据表明 心尖部钠离子进入的速度调节这些细胞的活性 转运蛋白。因此，远端对NA的重吸收能力 肾单位节段随着负荷的增加而增加 拥有量的减少导致负载的减少。这种形式的监管是 对盐分平衡有许多临床上重要的影响， 包括维持肾小球-肾小管平衡， 利尿剂抵抗现象与梗阻后的发展 利尿与肾小管下游萎缩的发生 肾小球疾病。此外，控制肾脏的钠排泄 参与了多种疾病状态的发病机制，如 高血压、肾病综合征和充血性心力衰竭。 目前，NA入境率调节的机制 对NA转运蛋白的活动知之甚少。建议进行的研究 将在分子水平上解决这个问题，使用具有良好特性的 集合管上皮细胞模型--A6细胞株 多孔支撑物。在他的细胞培养模型中发表了初步数据 证明阻止钠进入会导致打击 心尖钠通道和基底外侧通道的调节 Na/K-ATPase。此外，对应用钠离子测定的刺激- 调节这两条通路。最近编码三种蛋白质的cdna， α、β和伽马ENAC(上皮钠通道)一直是 进行了鉴定和克隆。所有低电导、高电导的活动 钠选择性，阿米洛利敏感的上皮钠通道来自 大脑皮层集合管可以用这些通道蛋白来解释。 这些蛋白质的同源物已经在A6细胞和 已被命名为XeNaC(非洲爪哇钠通道)。使用抗体 和Northern印迹探针到XeNaC通道，到阿尔法和 Na/K-ATPase的β亚基、心尖部钠进入的影响 论翻译、翻译和翻译后的调控 这些转运蛋白将被描述。

In kidney epithelial, vectorial sodium transport is a two step process. First, sodium entry occurs trough amiloride-blockable ion channels located in the apical membrane of sodium transporting cells. Second, the sodium is active transported out of the cells via a basolateral Na+/K+-ATPase. The net effect of these two processes, which occur in series, is the vectorial transport of sodium from the luminal compartment to the basolateral compartment. Previous data suggest that the rate of apical Na+ entry regulates the activity of these transporter proteins. Thus, the nA+ reabsorptive capacity of distal nephron segments increases in response to increased load and decreases in espouse to decreased load. This form of regulation is responsible from many clinically important effects on salt balance, including the maintenance of glomerular-tubular balance, the phenomenon of diuretic resistance, the development of post-obstructure diuresis and the occurrence of downstream tubular atrophy in glomerular disease. Moreover, the control of renal sodium excretion is involved in the pathogenesis of diverse disease states such as hypertension, nephrotic syndrome, and congestive heart failure. Currently, the mechanisms by which the rate of na+ entry regulates Na+ transporter activity are poorly understood. The proposed studies will address this issue at a molecular level using a well characterized model of collecting duct epithelial cells, the A6 cell line grown on porous supports. Published preliminary data in t his cell culture model demonstrates that blockage of Na+ entry result in striking on regulation of both the apical Na+ channel and the basolateral Na+/K+-ATPase. In addition, stimulation of aplical Na+ etry up- regulates both pathways. Recently cDNA encoding for three proteins, alpha, beta, and gamma EnaC (epithelial Na+ channel), has been identified and cloned. All of the activity of low conductance, highly sodium selective, amiloride-sensitive epithelial sodium channel from cortical collecting duct can be accounted for by these channel proteins. Homologues of these proteins have been described in A6 cells and have been termed XeNaC (Xenopus Na+ channel). Using antibody and northern blot probes to the XeNaC channel, and to the alpha and beta subunits of the Na+/K+-ATPase, the effect of apical Na+ entry on the transcriptional, translational and post-translational regulation of these transporter proteins will be described.