title: The epithelial sodium channel δ-subunit: new notes for an old song.
abstract: Amiloride-sensitive epithelial Na(+) channels (ENaCs) can be formed by different combinations of four homologous subunits, named α, β, γ, and δ. In addition to providing an apical entry pathway for transepithelial Na(+) reabsorption in tight epithelia such as the kidney distal tubule and collecting duct, ENaCs are also expressed in nonepithelial cells, where they may play different functional roles. The δ-subunit of ENaC was originally identified in humans and is able to form amiloride-sensitive Na(+) channels alone or in combination with β and γ, generally resembling the canonical kidney ENaC formed by α, β, and γ. However, δ differs from α in its tissue distribution and channel properties. Despite the low sequence conservation between α and δ (37% identity), their similar functional characteristics provide an excellent model for exploring structural correlates of specific ENaC biophysical and pharmacological properties. Moreover, the study of cellular mechanisms modulating the activity of different ENaC subunit combinations provides an opportunity to gain insight into the regulation of the channel. In this review, we examine the evolution of ENaC genes, channel subunit composition, the distinct functional and pharmacological features that δ confers to ENaC, and how this can be exploited to better understand this ion channel. Finally, we briefly consider possible functional roles of the ENaC δ-subunit.
authors.affiliation: Research Division, University Hospital N.S. Candelaria, Santa Cruz de Tenerife, Tenerife, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Giraldez
authors.forename: Patricio
authors.initials: P
authors.lastname: Rojas
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jou
authors.forename: Carlos
authors.initials: C
authors.lastname: Flores
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarez de la Rosa
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002918:Chymotrypsin / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D053503:Epithelial Sodium Channels; D012964:Sodium; D002918:Chymotrypsin