ArticleAmerican journal of physiology. Renal physiology2018
Potassium conservation is impaired in mice with reduced renal expression of Kir4.1.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- Stimulation of basolateral calcium-sensing receptor inhibits Kir4.1/Kir5.1 in the mouse distal convoluted tubule.American journal of physiology. Renal physiology · 2026Article
- Mechanistic Target of Rapamycin Complex 1 in Distal Convoluted Tubule and Renal Potassium Handling.Journal of the American Society of Nephrology : JASN · 2025Article
- Kinase Scaffold Cab39 Is Necessary for Phospho-Activation of the Thiazide-Sensitive NCC.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Inwardly rectifying KAmerican journal of physiology. Cell physiology · 2022Review
- FAM111A is dispensable for electrolyte homeostasis in mice.Scientific reports · 2022Article
- Dissecting the Effects of Aldosterone and Hypokalemia on the Epithelial NaFrontiers in physiology · 2022Article
- Renal calcium and magnesium handling in Gitelman syndrome.American journal of translational research · 2022Review
- Role of collecting duct principal cell NOS1β in sodium and potassium homeostasis.Physiological reports · 2021Article
- Deletion of renal Nedd4-2 abolishes the effect of high KAmerican journal of physiology. Renal physiology · 2021Article
- Dietary potassium and the kidney: lifesaving physiology.Clinical kidney journal · 2020Review
- Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule.Journal of the American Society of Nephrology : JASN · 2020Article
- Inhibition of AT2R and Bradykinin Type II Receptor (BK2R) Compromises High KHypertension (Dallas, Tex. : 1979) · 2020Article
- Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.Frontiers in physiology · 2020Review
- Intracellular chloride: a regulator of transepithelial transport in the distal nephron.Current opinion in nephrology and hypertension · 2019Review
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Authors and funding
11 authors at 2 institutions in 1 country.
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Abstract
To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression. Lethality by ~3 wk, however, limits the usefulness of this model, so we developed a kidney-specific Kir4.1 "knockdown" mouse (ksKD) using a cadherin 16 promoter and Cre-loxP methodology. These mice appeared normal and survived to adulthood. Kir4.1 protein expression was decreased ~50% vs. wild-type (WT) mice by immunoblotting, and immunofluorescence showed moderately reduced Kir4.1 staining in distal convoluted tubule that was minimal or absent in connecting tubule and cortical collecting duct. Under control conditions, the ksKD mice showed metabolic alkalosis and relative hypercalcemia but were normokalemic and mildly hypermagnesemic despite decreased NCC expression. In addition, the mice had a severe urinary concentrating defect associated with hypernatremia, enlarged kidneys with tubulocystic dilations, and reduced aquaporin-3 expression. On a K/Mg-free diet for 1 wk, however, ksKD mice showed marked hypokalemia (serum K: 1.5 ± 0.1 vs. 3.0 ± 0.1 mEq/l for WT), which was associated with renal K wasting (transtubular K gradient: 11.4 ± 0.8 vs. 1.6 ± 0.4 in WT). Phosphorylated-NCC expression increased in WT but not ksKD mice on the K/Mg-free diet, suggesting that loss of NCC adaptation underlies the hypokalemia. In conclusion, even modest reduction in Kir4.1 expression results in impaired K conservation, which appears to be mediated by reduced expression of activated NCC.
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