The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_6135A897B0FD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice.
Périodique
Journal of Clinical Investigation
Auteur(s)
Leviel F., Hübner C.A., Houillier P., Morla L., El Moghrabi S., Brideau G., Hatim H., Parker M.D., Kurth I., Kougioumtzes A., Sinning A., Pech V., Riemondy K.A., Miller R.L., Hummler E., Shull G.E., Aronson P.S., Doucet A., Wall S.M., Chambrey R., Eladari D.
ISSN
1558-8238
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
120
Numéro
5
Pages
1627-1635
Langue
anglais
Résumé
Regulation of sodium balance is a critical factor in the maintenance of euvolemia, and dysregulation of renal sodium excretion results in disorders of altered intravascular volume, such as hypertension. The amiloride-sensitive epithelial sodium channel (ENaC) is thought to be the only mechanism for sodium transport in the cortical collecting duct (CCD) of the kidney. However, it has been found that much of the sodium absorption in the CCD is actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule. In this study, we have demonstrated the presence of electroneutral, amiloride-resistant, thiazide-sensitive, transepithelial NaCl absorption in mouse CCDs, which persists even with genetic disruption of ENaC. Furthermore, hydrochlorothiazide (HCTZ) increased excretion of Na+ and Cl- in mice devoid of the thiazide target NCC, suggesting that an additional mechanism might account for this effect. Studies on isolated CCDs suggested that the parallel action of the Na+-driven Cl-/HCO3- exchanger (NDCBE/SLC4A8) and the Na+-independent Cl-/HCO3- exchanger (pendrin/SLC26A4) accounted for the electroneutral thiazide-sensitive sodium transport. Furthermore, genetic ablation of SLC4A8 abolished thiazide-sensitive NaCl transport in the CCD. These studies establish what we believe to be a novel role for NDCBE in mediating substantial Na+ reabsorption in the CCD and suggest a role for this transporter in the regulation of fluid homeostasis in mice.
Mots-clé
Amiloride/pharmacology, Animals, Chloride-Bicarbonate Antiporters/metabolism, Electrophysiology/methods, Hydrochlorothiazide/pharmacology, Kidney/metabolism, Kidney Tubules, Collecting/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Models, Biological, Oocytes/metabolism, Sodium/chemistry, Sodium Chloride Symporter Inhibitors/pharmacology, Sodium-Bicarbonate Symporters/metabolism, Xenopus
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/11/2010 16:50
Dernière modification de la notice
20/08/2019 14:18
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