Abstract: TH-OR23
KS-WNK1 Translates the Potassium Ingestion State to NCC Activity and Expression
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic and Clinical Research
November 04, 2021 | Location: Simulive, Virtual Only
Abstract Time: 04:30 PM - 06:00 PM
Category: Fluid, Electrolyte, and Acid-Base Disorders
- 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Bahena-López, Jessica Paola, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
- Chavez-Canales, Maria, Instituto de Investigaciones Biomedicas, UNAM, Mexico City, Mexico
- Lee, Ju Hye, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, DF, Mexico
- Murillo-de-Ozores, Adrian R., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, DF, Mexico
- Vázquez, Norma Hilda, Instituto de Investigaciones Biomedicas, UNAM, Mexico City, Mexico
- Ellison, David H., Oregon Health & Science University, Portland, Oregon, United States
- Castañeda-Bueno, Maria, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, DF, Mexico
- Gamba, Gerardo, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico
Background
The physioilogical role of KS-WNK1 in the distal convoluted tubule is not yet elucidated. KS-WNK1 upregulates NCC through activation of WNK4-SPAK pathway. Under low potassium diet, in which NCC activity is increased, KS-WNK1 is required for the formation of WNK bodies. However, changes in plasma K+ has not been observed in KS-WNK1 mice when compare to WT mice. We have recently shown that KS-WNK1 is highly sensitive to the CUL3-KLHL3 complex (JCI 2020) and its expression under control conditions is negligible, but it is increased under low potassium diet (AJP Renal 2021). In wild life, mammalians are exposed to cycles of no food and thus no K+ consumption for days, followed by a vast meet and thus K+ ingestion of in few hours. Because of the high sensitivity of KS-WNK1 expression to K+ intake, we assessed the expression of KS-WNK1 and NCC-SPAK modulation using a model to imitate what occurs in wild life.
Methods
We exposed wild type (WT) and KS-WNK1-KO (KS-KO) mice to 10 days of zero K+ diet (0KD), followed by high K+ diet (5 %) to imitate what occurs in the wild. Groups of mice were sacrificed before the HKD and at 12 or 24 hours of HKD. Blood was taken for electrolyte analysis and renal proteins were subjected to western blot using anti NCC, phospho-NCC, SPAK, phospho-SPAK, WNK4, WNK1 and actin antibodies.
Results
At the end of 10 days of 0KD, serum K+ was significantly lower in KS-KO mice than in WT mice (2.62±0.28 vs 3.40±0.22 mEq/L, p<0.05), while NCC phosphorylation was higher in the WT mice (1.00±0.32vs 0.58±0.06 a.u., p<0.05). At this point expression of KS-WNK1 was detected in WT, but not in KS-KO mice. In contrast, 24 hours after HKD, NCC expression and phosphorylation was not reduced in KS-KO mice, as ocurred in WT mice (WT 1.00±0.20 vs KS-KO 2.44±0.31, a.u., p<0.01 and 1.00±0.24 vs 3.07±0.56 mEq/l, p<0.05, respectively) and WT mice K+ excretion was higher, since the plasma K+ concentration was lower in WT than in KS-KO mice (6.02±0.62 vs 6.75±0.714 mEq/l, p<0.001).
Conclusion
Our data show that in WT mice during 0KD, activation of NCC was higher and after HKD, downregulation of NCC was more effective than in KS-KO mice. Thus, wild type mice are better suited to respond to extreme changes in potassium diet as those that probably occurs in wild life in mammals.
Funding
- NIDDK Support