ArticleKidney international2016
Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis.
Article in Kidney international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.
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Who cites it
156 citing papers in PubMed, 238 citations in OpenAlex.
- Chloride at the spotlight-but not alone: towards a multi-ionic diuretic strategy.Clinical kidney journal · 2026Review
- Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications.Biology of sex differences · 2026Review
- LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism.The Journal of physiology · 2026Article
- Pancreatitis: correcting CFTR expression and function as a promising effective treatment.Frontiers in physiology · 2026Review
- The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK.American journal of physiology. Renal physiology · 2025Article
- Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK.The Journal of physiology · 2025Article
- Mechanistic Target of Rapamycin Complex 1 in Distal Convoluted Tubule and Renal Potassium Handling.Journal of the American Society of Nephrology : JASN · 2025Article
- Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates.The Journal of clinical investigation · 2025Article
- The evolving concepts of KS-WNK1 effect on NCC activity.American journal of physiology. Renal physiology · 2025Review
- High chloride induces aldosterone resistance in the distal nephron.Acta physiologica (Oxford, England) · 2025Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Macrophage SPAK deletion limits a low potassium-induced kidney inflammatory program.American journal of physiology. Renal physiology · 2024Article
- Aldosterone-independent regulation of K + secretion in the distal nephron.Current opinion in nephrology and hypertension · 2024Review
- mTORc2 in Distal Convoluted Tubule and Renal K + Excretion during High Dietary K + Intake.Journal of the American Society of Nephrology : JASN · 2024Article
- Deletion of KS-WNK1 promotes NCC activation by increasing WNK1/4 abundance.American journal of physiology. Renal physiology · 2024Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2.Nature communications · 2024Article
- Monogenic Hypertension Linked to the Renin-Angiotensin-Aldosterone System.Anatolian journal of cardiology · 2024Article
- Potassium-Switch Signaling Pathway Dictates Acute Blood Pressure Response to Dietary Potassium.Hypertension (Dallas, Tex. : 1979) · 2024Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Dietary potassium deficiency activates thiazide-sensitive sodium chloride cotransport along the distal nephron. This may explain, in part, the hypertension and cardiovascular mortality observed in individuals who consume a low-potassium diet. Recent data suggest that plasma potassium affects the distal nephron directly by influencing intracellular chloride, an inhibitor of the with-no-lysine kinase (WNK)-Ste20p-related proline- and alanine-rich kinase (SPAK) pathway. As previous studies used extreme dietary manipulations, we sought to determine whether the relationship between potassium and NaCl cotransporter (NCC) is physiologically relevant and clarify the mechanisms involved. We report that modest changes in both dietary and plasma potassium affect NCC in vivo. Kinase assay studies showed that chloride inhibits WNK4 kinase activity at lower concentrations than it inhibits activity of WNK1 or WNK3. Also, chloride inhibited WNK4 within the range of distal cell chloride concentration. Mutation of a previously identified WNK chloride-binding motif converted WNK4 effects on SPAK from inhibitory to stimulatory in mammalian cells. Disruption of this motif in WNKs 1, 3, and 4 had different effects on NCC, consistent with the three WNKs having different chloride sensitivities. Thus, potassium effects on NCC are graded within the physiological range, which explains how unique chloride-sensing properties of WNK4 enable it to mediate effects of potassium on NCC in vivo.
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