title: Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Cheng
authors.forename: Michel
authors.initials: M
authors.lastname: Baum
authors.forename: Chou-Long
authors.initials: CL
authors.lastname: Huang
mesh_terms: D000042:Absorption / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000818:Animals; D005091:Exons; D005260:Female; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D010455:Peptides / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D017419:Potassium, Dietary / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D012964:Sodium / Q000378:metabolism*; D046509:Tissue Culture Techniques; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: C510693:Kcnj1 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D024661:Potassium Channels, Inwardly Rectifying; D017419:Potassium, Dietary; C064719:iberiotoxin; D012964:Sodium; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498744:Wnk1 protein, mouse; D011188:Potassium