Trafficking and Regulation of the Epithelial Na+ Channel

上皮Na通道的运输和调节

• 批准号: 6431083
• 负责人: JOHN P. JOHNSON
• 金额: $ 24.55万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6431083
• 关键词: MDCK cell; apical membrane; cell line; cellular polarity; epithelium; hormone regulation /control mechanism; intracellular transport; membrane activity; membrane biogenesis; protein localization; protein structure function; protein transport; renal tubular transport; saluresis; sodium channel

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.

描述（由申请人提供）：维持细胞外液体体积稳态对于血液动力学稳定性和肾脏异常至关重要 钠处理与心血管疾病和高血压有关。 肾脏中钠排泄的最终调节发生在远端 肾单位通过导电运输通过amiloride敏感上皮Na+ 频道（ENAC）。 ENAC表达和活性 上皮细胞是Na+重吸收的速率限制步骤，不仅在 肾脏收集管道，但也在气道上皮和结肠中。 ENAC功能的异常已在遗传形式中得到证明 高血压，肾盐浪费和囊性纤维化。长期目标的 这项研究是了解调节ENAC表达的因素 上皮细胞的顶膜和激素的机制， 生理条件和其他通道（例如囊性纤维化 跨膜调节剂，CFTR）控制ENAC函数。实验将定义 合成，顶端表达，内吞作用，回收和降解 极化肾细胞中的ENAC亚基。然后我们将研究一部小说 范式解释基底下ENAC亚基的非坐标调节 以及我们和其他研究人员的荷尔蒙刺激条件 观察到。