ArticleAmerican journal of physiology. Renal physiology2014
Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials.Journal of the American Heart Association · 2020Pooled it
- Why Your Mother Was Right: How Potassium Intake Reduces Blood Pressure.Transactions of the American Clinical and Climatological Association · 2015Trial
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- The exquisite link between potassium homeostasis regulation and cardiovascular health: exploration and analysis.Frontiers in physiology · 2026Review
- Excess dietary potassium raises blood pressure in male mice by an aldosterone-dependent increase in ENaC.Communications biology · 2025Article
- Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates.The Journal of clinical investigation · 2025Article
- Combination of genetic studies and animal modeling proposes TMPRSS9 as a candidate gene for serum KScientific reports · 2025Article
- Renal Ghrelin-Family GPR39 Receptor and Urinary Concentrating Ability.Journal of the American Society of Nephrology : JASN · 2025Article
- The evolving concepts of KS-WNK1 effect on NCC activity.American journal of physiology. Renal physiology · 2025Review
- mTORc2 in Distal Convoluted Tubule and Renal K + Excretion during High Dietary K + Intake.Journal of the American Society of Nephrology : JASN · 2024Article
- Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles.American journal of physiology. Renal physiology · 2024Article
- Chronic kidney disease increases the susceptibility to negative effects of low and high potassium intake.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Kinase Scaffold Cab39 Is Necessary for Phospho-Activation of the Thiazide-Sensitive NCC.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Modifying Dietary Sodium and Potassium Intake: An End to the 'Salt Wars'?Hypertension (Dallas, Tex. : 1979) · 2024Review
- KS-WNK1 is required for the renal response to extreme changes in potassium intake.American journal of physiology. Renal physiology · 2024Article
- Current perspective on circadian function of the kidney.American journal of physiology. Renal physiology · 2024Review
- Effect of low sodium and high potassium diet on lowering blood pressure and cardiovascular events.Clinical hypertension · 2024Review
- Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023Review
- Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation.JCI insight · 2023Article
- Renal KFrontiers in physiology · 2023Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Modulation of Na(+)-Cl(-) cotransporter (NCC) activity is essential to adjust K(+) excretion in the face of changes in dietary K(+) intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K(+) diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K(+)-citrate diets for 4 days. The low-K(+) diet decreased and high-K(+) diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr(44)/Thr(48)/Thr(53)) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser(383)/Ser(325)). The effect of the low-K(+) diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K(+) diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K(+) diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K(+)-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K(+) increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K(+) diet.
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