Vasopressin-stimulated CFTR Cl- currents are increased in the renal collecting duct cells of a mouse model of Liddle's syndrome.

Détails

ID Serval
serval:BIB_31574
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Vasopressin-stimulated CFTR Cl- currents are increased in the renal collecting duct cells of a mouse model of Liddle's syndrome.
Périodique
Journal of Physiology
Auteur(s)
Chang C.T., Bens M., Hummler E., Boulkroun S., Schild L., Teulon J., Rossier B.C., Vandewalle A.
ISSN
0022-3751
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
562
Numéro
1
Pages
271-284
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Liddle's syndrome is a genetic form of hypertension linked to Na(+) retention caused by activating mutations in the COOH terminus of the beta or gamma subunit of the epithelial sodium channel (ENaC). In this study, we used the short-circuit current (I(sc)) method to investigate the effects of deamino-8-d-arginine vasopressin (dDAVP) on Na(+) and Cl(-) fluxes in primary cultures of cortical collecting ducts (CCDs) microdissected from the kidneys of mice with Liddle's syndrome carrying a stop codon mutation, corresponding to the beta-ENaC R(566) stop mutation (L) found in the original pedigree. Compared to wild-type (+/+) CCD cells, untreated L/+ and L/L CCD cells exhibited 2.7- and 4.2-fold increases, respectively, in amiloride-sensitive (Ams) I(sc), reflecting ENaC-dependent Na(+) absorption. Short-term incubation with dDAVP caused a rapid and significant increase (approximately 2-fold) in Ams I(sc) in +/+, but not in L/+ or L/L CCD cells. In sharp contrast, dDAVP induced a greater increase in 5-nitro-2-(3-phenylpropamino)benzoate (NPPB)-inhibited apical Cl(-) currents in amiloride-treated L/L and L/+ cells than in their +/+ counterparts. I(sc) recordings performed under apical ion substituted conditions revealed that the dDAVP-stimulated apical secretion of Cl(-), which was absent in cultured CCDs lacking CFTR, was 1.8-fold greater in L/+ and 3.7-fold greater in L/L CCD cells than in their +/+ CCD counterparts. After the basal membrane had been permeabilized with nystatin and a basal-to-apical Cl(-) gradient had been imposed, dDAVP also stimulated larger Cl(-) currents across L/L and L/+ CCD layers than +/+ CCD layers. These findings demonstrate that vasopressin stimulates greater apical CFTR Cl(-) conductance in the renal CCD cells of mice with Liddle's syndrome than in wild-type mice. This effect could contribute to the enhanced NaCl reabsorption observed in the distal nephron of patients with Liddle's syndrome.
Mots-clé
Animals, Cells, Cultured, Chloride Channels, Chlorides, Codon, Cystic Fibrosis Transmembrane Conductance Regulator, Deamino Arginine Vasopressin, Electrophysiology, Epithelial Sodium Channel, Hypertension, Kidney Tubules, Collecting, Mice, Mice, Knockout, Nephrons, Nystatin, Organ Culture Techniques, Phenotype, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Sodium, Sodium Channels, Syndrome, Vasopressins
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 13:30
Dernière modification de la notice
20/08/2019 14:16
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