Genetic Disorders of Membrane Transport V. The epithelial sodium channel and its implication in human diseases
Genetic Disorders of Membrane Transport V. The epithelial sodium channel and its implication in human diseases
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DOI：
10.1152/ajpgi.1999.276.3.g567
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发表时间：
1999-03-01
影响因子：
4.5
通讯作者：
Horisberger, JD
中科院分区：
文献类型：
--
作者：
Hummler, E;Horisberger, JD
上皮Na+通道（ENaC）控制远端肾单位、远端结肠和气道中跨上皮Na+重吸收过程中的限速步骤。遗传性失盐综合征被归因于α-、β-或γ-ENaC亚基基因中的功能突变的丧失，而功能突变的获得（位于β-或γ-亚基的COOH末端）由于Na+潴留而导致高血压（利德尔综合征）。在小鼠中，基因靶向实验表明，除了肾脏耗盐表型，ENaC是新生小鼠肺液清除所必需的。α-亚基的破坏导致ENaC介导的Na+转运的完全废除，而β-或γ-亚基的敲除对肺中的液体清除只有轻微的影响。这三个亚基中的每一个的破坏都导致了类似于在人类中观察到的盐消耗综合征。
The epithelial Na+ channel (ENaC) controls the rate-limiting step in the process of transepithelial Na+ reabsorption in the distal nephron, the distal colon, and the airways. Hereditary salt-losing syndromes have been ascribed to loss of function mutations in the alpha-, beta-, or gamma-ENaC subunit genes, whereas gain of function mutations (located in the COOH terminus of the beta- or gamma-subunit) result in hypertension due to Na+ retention (Liddle's syndrome). In mice, gene-targeting experiments have shown that, in addition to the kidney salt-wasting phenotype, ENaC was essential for lung fluid clearance in newborn mice. Disruption of the alpha-subunit resulted in a complete abolition of ENaC-mediated Na+ transport, whereas knockout of the beta- or gamma-subunit had only minor effects on fluid clearance in lung. Disruption of each of the three subunits resulted in a salt-wasting syndrome similar to that observed in humans.