Trafficking and Regulation of the Epithelial Na+ Channel

描述（由申请人提供）：维持细胞外液量 稳态对于血流动力学稳定和肾功能异常是必不可少的。 钠处理与心血管疾病和高血压有关。 肾脏钠排泄的最终调节发生在远端 通过阿米洛利敏感上皮细胞传导性运输Na+ 通道（ENaC）。ENaC表达和活性在顶膜的 上皮细胞是Na+重吸收的限速步骤， 肾集合管，但在气道上皮和结肠。 ENaC功能的缺失已经在遗传形式的 高血压、肾性盐耗和囊性纤维化。的长期目标 本研究旨在了解ENaC表达的调控因素， 上皮细胞的顶膜和激素， 生理条件和其他通道（如囊性纤维化 跨膜调节因子（CFTR）控制ENaC功能。实验将定义 合成、顶端表达、内吞、再循环和降解 极化良好的肾细胞中的ENaC亚基。然后我们将研究一部小说 范式来解释ENaC亚基的非协调调节下的基础 以及我们和其他研究人员所遇到的 观察

DESCRIPTION (provided by applicant): Maintenance of extracellular fluid volume homeostasis is essential for hemodynamic stability, and abnormalities of renal sodium handling have been linked to cardiovascular disease and hypertension. Ultimate regulation of sodium excretion in the kidney occurs in the distal nephron via conductive transport through the amiloride sensitive epithelial Na+ channel (ENaC). ENaC expression and activity in the apical membrane of epithelial cells is the rate limiting step in Na+ reabsorption not only in kidney collecting duct, but in airway epithelia and colon as well. Abnormalities of ENaC function have been demonstrated in hereditary forms of hypertension, renal salt wasting, and cystic fibrosis. The long term goal of this research is to understand the factors that regulate ENaC expression in the apical membrane of epithelial cells and the mechanisms by which hormones, physiologic conditions and other channels (such as the cystic fibrosis transmembrane regulator, CFTR) control ENaC function. Experiments will define the synthesis, apical expression, endocytosis, recycling and degradation of ENaC subunits in well polarized kidney cells. We will then examine a novel paradigm to explain the non-coordinate regulation of ENaC subunits under basal and hormonally-stimulated conditions that we and other investigators have observed.