Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome

Détails

ID Serval
serval:BIB_8F9949FC3402
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome
Périodique
American Journal of Physiology Renal Physiology
Auteur(s)
Dahlmann A., Pradervand S., Hummler E., Rossier B. C., Frindt G., Palmer L. G.
ISSN
0363-6127
Statut éditorial
Publié
Date de publication
08/2003
Peer-reviewed
Oui
Volume
285
Numéro
2
Pages
F310-18
Notes
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. --- Old month value: Aug
Résumé
Currents through epithelial Na channels (ENaCs) were measured in the cortical collecting tubule (CCT) of mice expressing truncated beta-subunits of ENaC, reproducing one of the mutations found in human patients with Liddle's syndrome. Tubules were isolated from mice homozygous for the Liddle mutation (L/L) and from wild-type (WT) littermates. Amiloride-sensitive currents (INa) from single cells were recorded under whole cell clamp conditions. CCTs from mice kept under control conditions and fed a diet with normal levels of Na had very small INas (WT: 18 +/- 13 pA; L/L: 22 +/- 8 pA at Vm = -100 mV) that were not different in WT and L/L animals. However, the L/L mice had much larger currents when the animals were fed a low-Na diet (WT: 256 +/- 127 pA; L/L: 1,820 +/- 330 pA) or infused with aldosterone (WT: 285 +/- 63 pA; L/L: 1,600 +/- 280 pA). Currents from L/L mice were also larger when animals were pretreated with a high-K diet but not when the CCTs were stimulated in vitro with 8-CTP-cAMP. Noise analysis of amiloride-induced fluctuations in INa showed that single-channel currents at Vm = 0 mV were slightly smaller in L/L mice (WT: 0.33 pA; L/L: 0.24 pA). This difference could be attributed to a decrease in driving force since current-voltage analysis indicated that intracellular Na was increased in the L/L animals. Analysis of spontaneous channel noise indicated that the open probability was similar in the two genotypes(WT: 0.77; L/L: 0.80). Thus the increase in whole cell current is attributed to a difference in the density of conducting channels.
Mots-clé
Aldosterone/*pharmacology Amiloride/pharmacology Animals Disease Models, Animal Diuretics/pharmacology Epithelial Cells/drug effects/metabolism Epithelial Sodium Channel Hypertension/genetics/*metabolism Kidney/drug effects/*metabolism Membrane Potentials/drug effects/physiology Mice Mice, Inbred C57BL Mice, Mutant Strains Models, Biological Patch-Clamp Techniques Sodium Channels/genetics/*metabolism Sodium, Dietary/pharmacokinetics
Pubmed
Web of science
Création de la notice
24/01/2008 14:01
Dernière modification de la notice
03/03/2018 19:22
Données d'usage