ArticleAmerican journal of physiology. Renal physiology2011
Cellular and molecular basis of increased ammoniagenesis in potassium deprivation.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
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- Effects of proximal tubule NBCe1-A deletion on collecting duct intercalated cell responses to hypokalemia.American journal of physiology. Renal physiology · 2026Article
- The gene therapy for corneal pathology with novel nonsense cystinosis mouse lines created by CRISPR Gene Editing.The ocular surface · 2023Article
- Hypokalaemia - an active contributor to hepatic encephalopathy?Metabolic brain disease · 2023Article
- The proximal tubule through an NBCe1-dependent mechanism regulates collecting duct phenotypic and remodeling responses to acidosis.American journal of physiology. Renal physiology · 2023Article
- Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury.Cell reports · 2022Article
- Pendrin-null mice develop severe hypokalemia following dietary NaAmerican journal of physiology. Renal physiology · 2022Article
- Regulation of Rhcg, an ammonia transporter, by aldosterone in the kidney.The Journal of endocrinology · 2021Article
- Reversible Total Vision Loss Caused by Severe Metformin-associated Lactic Acidosis: A Case Report.Clinical practice and cases in emergency medicine · 2021Article
- Acetazolamide causes renalAmerican journal of physiology. Renal physiology · 2020Article
- NBCe1-A is required for the renal ammonia and KAmerican journal of physiology. Renal physiology · 2020Article
- Mechanism of Hyperkalemia-Induced Metabolic Acidosis.Journal of the American Society of Nephrology : JASN · 2018Article
- Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach.Digestive diseases and sciences · 2017Review
- Evidence for ammonium conductance in a mouse thick ascending limb cell line.Physiological reports · 2017Article
- Roles of renal ammonia metabolism other than in acid-base homeostasis.Pediatric nephrology (Berlin, Germany) · 2017Review
- Perioperative Care of Patients With Liver Cirrhosis: A Review.Health services insights · 2017Review
- Klotho/fibroblast growth factor 23- and PTH-independent estrogen receptor-α-mediated direct downregulation of NaPi-IIa by estrogen in the mouse kidney.American journal of physiology. Renal physiology · 2016Article
- Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.American journal of physiology. Renal physiology · 2016Article
- Nutritional assessment in cirrhotic patients with hepatic encephalopathy.World journal of hepatology · 2015Review
- Integrated compensatory network is activated in the absence of NCC phosphorylation.The Journal of clinical investigation · 2015Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypokalemia is associated with increased ammoniagenesis and stimulation of net acid excretion by the kidney in both humans and experimental animals. The molecular mechanisms underlying these effects remain unknown. Toward this end, rats were placed in metabolic cages and fed a control or K(+)-deficient diet (KD) for up to 6 days. Rats subjected to KD showed normal acid-base status and serum electrolytes composition. Interestingly, urinary NH(4)(+) excretion increased significantly and correlated with a parallel decrease in urine K(+) excretion in KD vs. control animals. Molecular studies showed a specific upregulation of the glutamine transporter SN1, which correlated with the upregulation of glutaminase (GA), glutamate dehydrogenase (GDH), and phosphoenolpyruvate carboxykinase. These effects occurred as early as day 2 of KD. Rats subjected to a combined KD and 280 mM NH(4)Cl loading (to induce metabolic acidosis) for 2 days showed an additive increase in NH(4)(+) excretion along with an additive increment in the expression levels of ammoniagenic enzymes GA and GDH compared with KD or NH(4)Cl loading alone. The incubation of cultured proximal tubule cells NRK 52E or LLC-PK(1) in low-K(+) medium did not affect NH(4)(+) production and did not alter the expression of SN1, GA, or GDH in NRK cells. These results demonstrate that K(+) deprivation stimulates ammoniagenesis through a coordinated upregulation of glutamine transporter SN1 and ammoniagenesis enzymes. This effect is developed before the onset of hypokalemia. The signaling pathway mediating these events is likely independent of KD-induced intracellular acidosis. Finally, the correlation between increased NH(4)(+) production and decreased K(+) excretion indicate that NH(4)(+) synthesis and transport likely play an important role in renal K(+) conservation during hypokalemia.
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