title: The sodium-activated sodium channel is expressed in the rat kidney thick ascending limb and collecting duct cells and is upregulated during high salt intake.
abstract: Increased dietary salt triggers oxidative stress and kidney injury in salt-sensitive hypertension; however, the mechanism for sensing increased extracellular Na(+) concentration ([Na(+)]) remains unclear. A Na(+)-activated Na(+) channel (Na sensor) described in the brain operates as a sensor of extracellular fluid [Na(+)]; nonetheless, its presence in the kidney has not been established. In the present study, we demonstrated the gene expression of the Na sensor by RT-PCR and Western blotting in the Sprague-Dawley rat kidney. Using immunofluorescence, the Na sensor was localized to the luminal side in tubular epithelial cells of collecting ducts colocalizing with aquaporin-2, a marker of principal cells, and in thick ascending limb, colocalizing with the glycoprotein Tamm-Horsfall. To determine the effect of a high-salt diet (HSD) on Na sensor gene expression, we quantified its transcript and protein levels primarily in renal medullas from control rats and rats subjected to 8% NaCl for 7 days (n = 5). HSD increased Na sensor expression levels (mRNA: from 1.2 ± 0.2 to 5.1 ± 1.3 au; protein: from 0.98 ± 0.15 to 1.74 ± 0.28 au P < 0.05) in the kidney medulla, but not in the cortex. These data indicate that rat kidney epithelial cells of the thick ascending limb and principal cells of the collecting duct possess a Na sensor that is upregulated by HSD, suggesting an important role in monitoring changes in tubular fluid [Na(+)].
authors.affiliation: Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA. lara@icb.ufrj.br
authors.forename: Lucienne S
authors.initials: LS
authors.lastname: Lara
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Satou
authors.forename: Camille R T
authors.initials: CR
authors.lastname: Bourgeois
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Gonzalez
authors.forename: Andrea
authors.initials: A
authors.lastname: Zsombok
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D015854:Up-Regulation
chemical_list: D051399:Aquaporin 2; D015222:Sodium Channels; D017673:Sodium Chloride, Dietary