KS-WNK1 is Required for the Renal Response to Extreme Changes in Potassium Intake

• Published in: American journal of physiology. Renal physiology Vol. 326; no. 3; p. F460
• Main Authors: Bahena-Lopez, Jessica Paola, Vergara, Laura, De la Peña, Valeria, Gutiérrez-Gallardo, Miguel A, López-Ibargüen, Paulina, García, Janeth Alejandra, Carbajal-Contreras, Héctor, Vázquez, Norma, Rincón-Heredia, Ruth, Masso, Felipe, Bobadilla, Sr, Norma A, Castañeda-Bueno, María, Ellison, David H, Gamba, Gerardo, Chávez-Canales, María
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.03.2024
• Subjects: Dephosphorylation; Diet; Excretion; Genotypes; Kidneys; Nutrient deficiency; Phosphorylation; Plasma levels; Potassium; Renal function; Potassium renal excretion; Na+-Cl- cotransporter (NCC); Distal convoluted tubule; WNK kinase
• ISSN: 1931-857X; 1522-1466; 1522-1466
• DOI: 10.1152/ajprenal.00235.2023

KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest that it could play a role in regulating potassium renal excretion by modulating the activity of the Na -Cl cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low potassium diet. In this study, we investigated the role of KS-WNK1 in regulating potassium excretion under extreme changes in potassium intake. After following a zero-potassium diet (0KD) for 10 days, KS-WNK1 mice had lower plasma levels of K and Cl , while exhibiting higher urinary excretion of Na , Cl , and K compared to KS-WNK1 mice. After 10 days of 0KD or normal-potassium diet (NKD), all mice were challenged with a high-potassium diet (HKD). Plasma K levels markedly increased after the HKD challenge only in mice previously fed with 0KD, regardless of genotype. KSWNK1 mice adapt better to HKD-challenge than KS-WNK1 mice after a potassium-retaining state. The difference in the pNCC/NCC ratio between KS-WNK1 and KS-WNK1 mice after 0KD and HKD indicates a role for KS-WNK1 in both, NCC phosphorylation and dephosphorylation. These observations show that KS-WNK1 helps the DCT to respond to extreme changes in potassium intake, such as those occurring in wildlife.