title: Disorders of the epithelial Na(+) channel in Liddle's syndrome and autosomal recessive pseudohypoaldosteronism type 1.
abstract: The epithelial Na(+) channel (ENaC) is the key step in many Na(+)-absorptive epithelia, such as kidney and distal colon, that controls the overall rate of transepithelial Na(+) transport. ENaC is composed of three homologous subunits, alpha, beta, and gamma. The alpha subunit is the key subunit for the formation of a functional ion channel, while the beta and gamma subunits can greatly potentiate the level of expressed Na(+) currents. ENaCs belong to the recently identified DEG/ENaC supergene family, sharing the same basic structure with cytoplasmic amino and carboxy termini, two transmembrane regions, and a large extracellular loop. The human ENaC genes have been cloned, and using genetic linkage analysis the involvement of ENaC gene mutations in two distinct human diseases, Liddle's syndrome and autosomal recessive pseudohypoaldosteronism type 1 (PHA-1), has been demonstrated. In Liddle's syndrome, gain-of-function mutations in the beta or gamma ENaC subunits have been found; all identified mutations so far reside in the carboxy terminus of the protein, either deleting or modifying the functionally important PY motif. In PHA-1, loss-of-function mutations in the alpha, beta, or gamma subunits have been found; these mutations either truncate a significant portion of the structure or modify an amino acid that plays an important role in channel function. In this review, our current understanding about ENaC and the pathophysiology of Liddle's syndrome and PHA-1 caused by ENaC mutations will be discussed.
authors.affiliation: Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, 35294, USA. yoh@uab.edu
authors.forename: Y S
authors.initials: YS
authors.lastname: Oh
authors.forename: D G
authors.initials: DG
authors.lastname: Warnock
mesh_terms: D000818:Animals; D053503:Epithelial Sodium Channels; D005808:Genes, Recessive; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D011546:Pseudohypoaldosteronism / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D015222:Sodium Channels