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Journal articles
Defective bicarbonate reabsorption in Kir4.2 potassium channel deficient mice impairs acid-base balance and ammonia excretion: Kir4.2 and renal ammoniagenesis
Abstract : The kidneys excrete the daily acid load mainly by generating and excreting ammonia but the underlying molecular mechanisms are not fully understood. Here we evaluated the role of the inwardly rectifying potassium channel subunit Kir4.2 (Kcnj15 gene product) in this process. In mice, Kir4.2 was present exclusively at the basolateral membrane of proximal tubular cells and disruption of Kcnj15 caused a hyperchloremic metabolic acidosis associated with a reduced threshold for bicarbonate in the absence of a generalized proximal tubule dysfunction. Urinary ammonium excretion rates in Kcnj15- deleted mice were inappropriate to acidosis under basal and acid-loading conditions, and not related to a failure to acidify urine or a reduced expression of ammonia transporters in the collecting duct. In contrast, the expression of key proteins involved in ammonia metabolism and secretion by proximal cells, namely the glutamine transporter SNAT3, the phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase enzymes, and the sodium-proton exchanger NHE-3 was inappropriate in Kcnj15-deleted mice. Additionally, Kcnj15 deletion depolarized the proximal cell membrane by decreasing the barium-sensitive component of the potassium conductance and caused an intracellular alkalinization. Thus, the Kir4.2 potassium channel subunit is a newly recognized regulator of proximal ammonia metabolism. The kidney consequences of its loss of function in mice support the proposal for KCNJ15 as a molecular basis for human isolated proximal renal tubular acidosis.
Cited literature [72 references]
https://www.hal.inserm.fr/inserm-02447624
Contributor : Marc Paulais <>
Submitted on : Thursday, February 13, 2020 - 4:45:46 PM
Last modification on : Monday, December 14, 2020 - 9:47:25 AM
Long-term archiving on: : Thursday, May 14, 2020 - 4:55:20 PM
Contributor : Marc Paulais <>
Submitted on : Thursday, February 13, 2020 - 4:45:46 PM
Last modification on : Monday, December 14, 2020 - 9:47:25 AM
Long-term archiving on: : Thursday, May 14, 2020 - 4:55:20 PM
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Bignon et al, Kidney Internati...
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