title: An oxygen-sensitive mechanism in regulation of epithelial sodium channel.
abstract: Epithelial sodium channels (ENaCs) are of immense importance, controlling Na(+) transport across epithelia and thus playing a central role in all aspects of fluid clearance as well as numerous other functions. Regulation of these channels is critical. Here, we show that haem, a regulator of Na(+) transport, directly influences ENaC activity, decreasing channel-open probability (but not unitary conductance) in inside-out patches (but not outside-out). Conversely, exposure to the protein in the presence of NADPH and at normoxic O(2) tension (requirements for activity of hemeoxygenase) increases channel activity. CO, a product of hemeoxygenase activity, activated ENaC in a manner similar to that of haem plus NADPH. However, under hypoxic conditions, inhibition of ENaC by haem occurred even in the presence of NADPH. These data demonstrate a potent, O(2)-sensitive mechanism for regulation of ENaC, in which hemeoxygenase acts as the O(2) sensor, its substrate and product inhibiting and stimulating (respectively) the activity of ENaC.
authors.affiliation: Departments of Physiology and Bioscience, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Stephen
authors.initials: S
authors.lastname: Publicover
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D053503:Epithelial Sodium Channels / Q000502:physiology*; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051379:Mice; D009249:NADP / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D018408:Patch-Clamp Techniques
chemical_list: D053503:Epithelial Sodium Channels; D006418:Heme; D009249:NADP; D006419:Heme Oxygenase (Decyclizing); D010100:Oxygen