TY - JOUR
T1 - Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct
AU - Cheng, Chih Jen
AU - Baum, Michel
AU - Huang, Chou Long
PY - 2013/2/15
Y1 - 2013/2/15
N2 - 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.
AB - 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.
KW - Cortical collecting duct
KW - In vitro microperfusion
KW - Kidney-specific WNK1
KW - WNK kinase
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UR - http://www.scopus.com/inward/citedby.url?scp=84874080354&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00589.2012
DO - 10.1152/ajprenal.00589.2012
M3 - Article
C2 - 23195681
AN - SCOPUS:84874080354
SN - 1931-857X
VL - 304
SP - F397-F402
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 4
ER -