Genetic Disorders of Membrane Transport V. The epithelial sodium channel and its implication in human diseases*

Hummler, Edith, and Jean-Daniel Horisberger. Genetic Disorders of Membrane Transport. V. The epithelial sodium channel and its implication in human diseases. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G567–G571, 1999.—The epithelial Na1 channel (ENaC) controls the ratelimiting step in the process of transepithelial Na1 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 a-, b-, or g-ENaC subunit genes, whereas gain of function mutations (located in the COOH terminus of the bor g-subunit) result in hypertension due to Na1 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 a-subunit resulted in a complete abolition of ENaC-mediated Na1 transport, whereas knockout of the bor g-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.