Liddle's syndrome is a genetic form of hypertension linked to Na+ retention caused by activating mutations in the COOH terminus of the β or γ subunit of the epithelial sodium channel (ENaC). In this study, we used the short-circuit current (Isc) 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 β-ENaC R566 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) Isc, reflecting ENaC-dependent Na+ absorption. Short-term incubation with dDAVP caused a rapid and significant increase (∼2-fold) in Ams Isc 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. Isc 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
To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.