title: Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation.
abstract: In distal colon, the limiting factor for Na(+) absorption is represented by the epithelial sodium channel (ENaC). During absorption, high transepithelial Na(+) gradients are observed. In human colon and in HT-29/B6-GR cells, we investigated whether Na(+) back-leakage is prevented by paracellular sealing. Tissues and cells were incubated with corticosteroids. Barrier properties were analyzed in electrophysiological experiments. Subsequently, analysis of ENaC and tight junction protein expression, localization, and regulation was performed. In colon, nanomolar aldosterone induced sodium absorption via ENaC. Concomitantly, paracellular (22)Na(+) permeability was reduced by half and claudin-8 within the tight junction complex was nearly doubled. Real-time PCR validated an increase of claudin-8 transcripts. Two-path impedance spectroscopy following ENaC induction in HT-29/B6-GR revealed a specific increase of paracellular resistance. These results represent an important physiological implication: Na(+) absorption is paralleled by claudin-8-mediated sealing of the paracellular barrier to prevent Na(+) back-leakage, supporting steep Na(+) gradients in distal colon.
authors.affiliation: Institute of Clinical Physiology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Salah
authors.initials: S
authors.lastname: Amasheh
authors.forename: Susanne
authors.initials: S
authors.lastname: Milatz
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Krug
authors.forename: Maike
authors.initials: M
authors.lastname: Bergs
authors.forename: Maren
authors.initials: M
authors.lastname: Amasheh
authors.forename: Jörg-Dieter
authors.initials: JD
authors.lastname: Schulzke
authors.forename: Michael
authors.initials: M
authors.lastname: Fromm
mesh_terms: D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D057167:Claudins; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D008565:Membrane Proteins / Q000378:metabolism*; D062793:Occludin; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D000450:Aldosterone; D012964:Sodium; C502011:claudin 8