Abstract: TH-PO513
Response of WNK-1 Intercalated Cell (IC) Knock-out Mice to a High K+ Diet
Session Information
- Fluid and Electrolytes: Basic - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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