Loss of WNK3 is Compensated for by the WNK1/SPAK Axis in the Kidney of the Mouse.

Loss of WNK3 is Compensated for by the WNK1/SPAK Axis in the Kidney of the Mouse. Am J Physiol Renal Physiol. 2013 Feb 20; Authors: Mederle K, Mutig K, Paliege A, Carota I, Bachmann S, Castrop H, Oppermann M Abstract WNK3 kinase is expressed throughout the nephron and acts as a positive regulator of NKCC2 and NCC in vitro. Here we addressed the in vivo relevance of WNK3 using WNK3-deficient mice. The net tubular function was similar in WT and WNK3-/- mice as assessed by determination of 24-hr urine output (1.63±.06 in WT and 1.55±.1 mL in WNK3-/-, n=16; p=.42) and ambient urine osmolarity (1804±62 in WT vs. 1819±61 mosmol/kg in WNNK3-/-, n=40; p=.86). Water restriction increased urine osmolarity similarly in both genotypes to 3440±220 and 3200±180 mosmol/kg in WT and WNK3-/- mice, respectively (n=11; p=.41). GFR (343±22 vs. 315±13 mL/min), renal blood flow (1.35±.1 vs. 1.42±.04 ml), and plasma renin concentration (94±18 vs. 80±13 ng AngI/mL/hr) were similar between WT and WNK3-/- mice (n=13; p=.54). WNK1 was markedly upregulated in WNK3-deficient mice. When the mice were fed a salt-restricted diet (0.02% NaCl [w/w]) the levels of pSPAK/OSR1, pNKCC2, and pNCC were enhanced in both genotypes compared with the baseline conditions, with the levels in WNK3-/- exceeding those in WT mice. The upregulation of pSPAK/OSR1, pNKCC2, and pNCC in WNK3-/- mice relative to the levels in wild type mice when fed a low salt diet was paralleled by an ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research