Hummler E, Barker P, Gatzy J, Beermann F, Verdumo C, Schmidt A, Boucher R, Rossier B C
Institut de Pharmacologie et de Toxicologie de l'Université, Lausanne, Switzerland.
Nat Genet. 1996 Mar;12(3):325-8. doi: 10.1038/ng0396-325.
The amiloride-sensitive epithelial sodium channel, ENaC, is a heteromultimeric protein made up of three homologous subunits (alpha, beta and gamma) (1,2). In vitro, assembly and expression of functional active sodium channels in the Xenopus oocyte is strictly dependent on alpha-ENaC--the beta and gamma subunits by themselves are unable to induce an amiloride-sensitive sodium current in this heterologous expression system (2). In vivo, ENaC constitutes the limiting step for sodium absorption in epithelial cells that line the distal renal tubule, distal colon and the duct of several exocrine glands. The adult lung expresses alpha, beta and gamma ENaC (3,4), and an amiloride-sensitive electrogenic sodium reabsorption has been documented in upper and lower airways (3-7), but it is not established whether this sodium transport is mediated by ENaC in vivo. We inactivated the mouse alpha-ENaC gene by gene targeting. Amiloride-sensitive electrogenic Na+ transport was abolished in airway epithelia from alpha-ENaC(-/-) mice. Alpha-ENaC(-/-) neonates developed respiratory distress and died within 40 h of birth from failure to clear their lungs of liquid. This study shows that ENaC plays a critical role in the adaptation of the newborn lung to air breathing.
氨氯地平敏感的上皮钠通道（ENaC）是一种异源多聚体蛋白，由三个同源亚基（α、β和γ）组成（1,2）。在体外，非洲爪蟾卵母细胞中功能性活性钠通道的组装和表达严格依赖于α-ENaC——β和γ亚基自身无法在这种异源表达系统中诱导出氨氯地平敏感的钠电流（2）。在体内，ENaC是远端肾小管、远端结肠和几种外分泌腺导管内衬上皮细胞中钠吸收的限速步骤。成年肺表达α、β和γ ENaC（3,4），并且在上、下呼吸道中已记录到氨氯地平敏感的电生性钠重吸收（3-7），但在体内这种钠转运是否由ENaC介导尚未确定。我们通过基因打靶使小鼠α-ENaC基因失活。来自α-ENaC（-/-）小鼠的气道上皮细胞中氨氯地平敏感的电生性Na+转运被消除。α-ENaC（-/-）新生小鼠出现呼吸窘迫，并在出生后40小时内死于无法清除肺内液体。这项研究表明，ENaC在新生肺适应空气呼吸中起关键作用。
