title: Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Weill Medical College of Cornell Univ., 1300 York Ave., New York, NY 10021, USA.
authors.forename: Anke
authors.initials: A
authors.lastname: Dahlmann
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pradervand
authors.forename: Edith
authors.initials: E
authors.lastname: Hummler
authors.forename: Bernard C
authors.initials: BC
authors.lastname: Rossier
authors.forename: Gustavo
authors.initials: G
authors.lastname: Frindt
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Palmer
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D053503:Epithelial Sodium Channels; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D012982:Sodium, Dietary / Q000493:pharmacokinetics
chemical_list: D004232:Diuretics; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D012982:Sodium, Dietary; D000450:Aldosterone; D000584:Amiloride