title: ENaC structure and function in the wake of a resolved structure of a family member.
abstract: Our understanding of epithelial Na(+) channel (ENaC) structure and function has been profoundly impacted by the resolved structure of the homologous acid-sensing ion channel 1 (ASIC1). The structure of the extracellular and pore regions provide insight into channel assembly, processing, and the ability of these channels to sense the external environment. The absence of intracellular structures precludes insight into important interactions with intracellular factors that regulate trafficking and function. The primary sequences of ASIC1 and ENaC subunits are well conserved within the regions that are within or in close proximity to the plasma membrane, but poorly conserved in peripheral domains that may functionally differentiate family members. This review examines functional data, including ion selectivity, gating, and amiloride block, in light of the resolved ASIC1 structure.
authors.affiliation: Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. obk2@pitt.edu
authors.forename: Ossama B
authors.initials: OB
authors.lastname: Kashlan
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kleyman
mesh_terms: D062565:Acid Sensing Ion Channels; D000584:Amiloride / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002712:Chlorides / Q000502:physiology; D017124:Conserved Sequence; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017386:Sequence Homology, Amino Acid; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D002712:Chlorides; D053503:Epithelial Sodium Channels; D009419:Nerve Tissue Proteins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000584:Amiloride