ArticleThe Journal of clinical investigation2023
Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Research progress and hotspots of the impact of Mediterranean diet on brain health from 2005 to 2025: a bibliometric and visualization analysis.Frontiers in nutrition · 2026Pooled it
- A bibliometric analysis of the Mediterranean diet in metabolic syndrome (2015-2025).Frontiers in nutrition · 2026Pooled it
- DASH-Patterned Groceries and Effects on Blood Pressure: The GoFresh Randomized Clinical Trial.JAMA · 2026Trial
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- The Benefits of Non-Pharmaceutic Interventions on Intrinsic Capacity in Insulin-Resistant Adult and Geriatric Populations-A Narrative Review.Journal of clinical medicine · 2026Review
- Mechanistic target of rapamycin complex-1 plays a role in inhibiting kidney KAmerican journal of physiology. Renal physiology · 2026Article
- The tumor suppressor NDRG2 recruits protein phosphatase 2A to suppress STAT5 phosphorylation in adult T-cell leukemia/lymphoma.The Journal of biological chemistry · 2026Article
- Potassium and the kidney.Nature reviews. Nephrology · 2026Review
- New evidence linking lifestyle factors to blood pressure: Focus on 2024 findings.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- How Does Dietary Potassium Influence BP?Journal of the American Society of Nephrology : JASN · 2026Review
- Dietary potassium restriction causes hypercalciuria, hypocalcemia, and bone loss in male mice.JCI insight · 2026Article
- [Consensus recommendations on the diagnosis and treatment of hyperkalemia of the Austrian Society of Nephrology 2026].Wiener klinische Wochenschrift · 2026Review
- Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications.Biology of sex differences · 2026Review
- The exquisite link between potassium homeostasis regulation and cardiovascular health: exploration and analysis.Frontiers in physiology · 2026Review
- The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK.American journal of physiology. Renal physiology · 2025Article
- Excess dietary potassium raises blood pressure in male mice by an aldosterone-dependent increase in ENaC.Communications biology · 2025Article
- Dietary Potassium Synergistically Enhances Anti-Obesity Efficacy of Garcinia Cambogia Complex in High-Fat Diet-Induced Obese Mice.Biomolecules & therapeutics · 2025Article
- KS-WNK1 augments the effects of dietary potassium intake on renal sodium chloride reabsorption.The Journal of clinical investigation · 2025Article
- Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates.The Journal of clinical investigation · 2025Article
- mTORc2 in Distal Convoluted Tubule and Renal K + Excretion during High Dietary K + Intake.Journal of the American Society of Nephrology : JASN · 2024Article
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8 authors at 3 institutions in 3 countries.
Funding
Abstract
Consumption of low dietary potassium, common with ultraprocessed foods, activates the thiazide-sensitive sodium chloride cotransporter (NCC) via the with no (K) lysine kinase/STE20/SPS1-related proline-alanine-rich protein kinase (WNK/SPAK) pathway to induce salt retention and elevate blood pressure (BP). However, it remains unclear how high-potassium "DASH-like" diets (dietary approaches to stop hypertension) inactivate the cotransporter and whether this decreases BP. A transcriptomics screen identified Ppp1Ca, encoding PP1A, as a potassium-upregulated gene, and its negative regulator Ppp1r1a, as a potassium-suppressed gene in the kidney. PP1A directly binds to and dephosphorylates NCC when extracellular potassium is elevated. Using mice genetically engineered to constitutively activate the NCC-regulatory kinase SPAK and thereby eliminate the effects of the WNK/SPAK kinase cascade, we confirmed that PP1A dephosphorylated NCC directly in a potassium-regulated manner. Prior adaptation to a high-potassium diet was required to maximally dephosphorylate NCC and lower BP in constitutively active SPAK mice, and this was associated with potassium-dependent suppression of Ppp1r1a and dephosphorylation of its cognate protein, inhibitory subunit 1 (I1). In conclusion, potassium-dependent activation of PP1A and inhibition of I1 drove NCC dephosphorylation, providing a mechanism to explain how high dietary K+ lowers BP. Shifting signaling of PP1A in favor of activation of WNK/SPAK may provide an improved therapeutic approach for treating salt-sensitive hypertension.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.