Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation.
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.
Amasheh
Salah
S
Institute of Clinical Physiology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Milatz
Susanne
S
Krug
Susanne M
SM
Bergs
Maike
M
Amasheh
Maren
M
Schulzke
Jörg-Dieter
JD
Fromm
Michael
M
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
D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D000450:Aldosterone; D012964:Sodium; C502011:claudin 8