ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO513

Response of WNK-1 Intercalated Cell (IC) Knock-out Mice to a High K+ Diet

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Ray, Evan C., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Carrisoza-Gaytan, Rolando, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Marciszyn, Allison L., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Nkashama, Lubika J., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Chen, Jingxin, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Winfrey, Aaliyah, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Flores, Daniel, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Wu, Peng, New York Medical College, Valhalla, New York, United States
  • Wang, WenHui, New York Medical College, Valhalla, New York, United States
  • Huang, Chou-Long, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
  • Kohan, Donald E., University of Utah Health Sciences Center, Salt Lake City, Utah, United States
  • Subramanya, Arohan R., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Satlin, Lisa M., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Kleyman, Thomas R., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Background

In the cortical collecting duct (CCD), IC BK channels mediate flow-induced K+ secretion (FIKS) and contribute to the renal adaptation to dietary K+ intake. IC BK channel apical expression and activity are enhanced by a high K+ diet. In HEK cells, L-WNK1 also stimulates BK channel expression and activity. The observation that L-WNK1 expression is enhanced in the CCD of rabbits on a high K+ (HK) diet suggests that L-WNK1 contributes to modulation of the BK channel by dietary K+. We asked whether IC L-WNK1 expression is necessary for enhanced BK activity and renal adaptation to a HK diet.

Methods

We generated mice with IC-specific deletion of L-WNK1 (IC-WNK1-KO) by crossing floxed L-WNK1 mice with V-ATPase Cre mice. KO and floxed control mice were placed on a HK diet for 10 days to maximally stimulate BK channel expression.

Results

Perforated whole-cell recordings of ICs in CCDs from IC-WNK1-KO mice revealed significant reduction in charybdotoxin (CbTX)-sensitive K+ currents vs. controls (440 +/- 64 pA vs. 703 +/- 92 pA, respectively; N = 4 and 4; p =0.003). IC-WNK1-KO mice also exhibited higher blood [K+] vs. controls (5.6 +/- 1.0 vs. 5.0 +/- 0.9 mEq/L; N = 21 and 19; p = 0.048). Despite the increased blood [K+] in the IC-WNK1-KO mice, urinary K+ excretion in response to an intra-peritoneal bolus of 10% vol/wt 0.9% saline was similar in KOs and controls (4.5 +/- 9.0 vs. 4.6 +/- 7.0 mcmol/hr/g; N = 9 and 7).

Conclusion

The observations that IC-WNK1-KO mice have higher blood [K+] and reduced CbTX-sensitive currents in CCD ICs indicate that these mice have a defect in urinary K+ secretion, highlighting the importance of L-WNK1 in ICs for adaptation to a HK diet. The retained capacity for K secretion in response to a saline load suggests upregulation of other K+ secretory processes.

Funding

  • NIDDK Support