PubMed 23195681

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir1.1

Title: Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct.

Authors: Chih-Jen Cheng, Michel Baum, Chou-Long Huang

Journal, date & volume: Am. J. Physiol. Renal Physiol., 2013 Feb 15 , 304, F397-402

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Kidney-specific with-no-lysine kinase 1 (KS-WNK1) is a kinase-deficient variant of WNK1 that is expressed exclusively in the kidney. It is abundantly expressed in the distal convoluted tubule (DCT) and to a lesser extent in the cortical thick ascending limb (cTAL), connecting tubule, and cortical collecting duct (CCD). KS-WNK1 inhibits Na(+)-K(+)-2Cl(-)- and sodium chloride cotransporter-mediated Na(+) reabsorption in cTAL and DCT, respectively. Here, we investigated the role of KS-WNK1 in regulating Na(+) and K(+) transport in CCD using in vitro microperfusion of tubules isolated from KS-WNK1 knockout mice and control wild-type littermates. Because baseline K(+) secretion and Na(+) reabsorption were negligible in mouse CCD, we studied tubules isolated from mice fed a high-K(+) diet for 2 wk. Compared with that in wild-type tubules, K(+) secretion was reduced in KS-WNK1 knockout CCD perfused at a low luminal fluid rate of ~1.5 nl/min. Na(+) reabsorption and the lumen-negative transepithelial potential difference were also lower in the KS-WNK1 knockout CCD compared with control CCD. Increasing the perfusion rate to ~5.5 nl/min stimulated K(+) secretion in the wild-type as well as knockout CCD. The magnitudes of flow-stimulated increase in K(+) secretion were similar in wild-type and knockout CCD. Maxi-K(+) channel inhibitor iberiotoxin had no effect on K(+) secretion when tubules were perfused at ~1.5 nl/min, but completely abrogated the flow-dependent increase in K(+) secretion at ~5.5 nl/min. These findings support the notion that KS-WNK1 stimulates ROMK-mediated K(+) secretion, but not flow-dependent K(+) secretion mediated by maxi-K(+) channels in CCD. In addition, KS-WNK1 plays a role in regulating Na(+) transport in the CCD.