title: The heterotetrameric architecture of the epithelial sodium channel (ENaC).
abstract: The epithelial sodium channel (ENaC) is a key element for the maintenance of sodium balance and the regulation of blood pressure. Three homologous ENaC subunits (alpha, beta and gamma) assemble to form a highly Na+-selective channel. However, the subunit stoichiometry of ENaC has not yet been solved. Quantitative analysis of cell surface expression of ENaC alpha, beta and gamma subunits shows that they assemble according to a fixed stoichiometry, with alpha ENaC as the most abundant subunit. Functional assays based on differential sensitivities to channel blockers elicited by mutations tagging each alpha, beta and gamma subunit are consistent with a four subunit stoichiometry composed of two alpha, one beta and one gamma. Expression of concatameric cDNA constructs made of different combinations of ENaC subunits confirmed the four subunit channel stoichiometry and showed that the arrangement of the subunits around the channel pore consists of two alpha subunits separated by beta and gamma subunits.
authors.affiliation: Institut de Pharmacologie et Toxicologie de l'Université, Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Firsov
authors.forename: I
authors.initials: I
authors.lastname: Gautschi
authors.forename: A M
authors.initials: AM
authors.lastname: Merillat
authors.forename: B C
authors.initials: BC
authors.lastname: Rossier
authors.forename: L
authors.initials: L
authors.lastname: Schild
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D053503:Epithelial Sodium Channels; D008024:Ligands; D046911:Macromolecular Substances; D016296:Mutagenesis; D009865:Oocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
chemical_list: D053503:Epithelial Sodium Channels; D008024:Ligands; D046911:Macromolecular Substances; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000584:Amiloride