Role of Ammonia in the Renal Potassium Response to Dietary K<sup>+</sup> Deficiency
November 08, 2019 | 10:00 AM - 12:00 PM
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Role of Ammonia in the Renal Potassium Response to Dietary K+ Deficiency
Fluid and Electrolytes: Basic - I
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid and Electrolytes
- 901 Fluid and Electrolytes: Basic
- Lee, Hyun-Wook, University of Florida, Gainesville, Florida, United States
- Harris, Autumn N., University of Florida, Gainesville, Florida, United States
- Romero, Michael F., Mayo Clinic College of Medicine, Rochester, Minnesota, United States
- Welling, Paul A., University of Maryland School of Medicine, Baltimore, Maryland, United States
- Verlander, Jill W., University of Florida, Gainesville, Florida, United States
- Weiner, I. David, University of Florida, Gainesville, Florida, United States
Autumn N. Harris,
Michael F. Romero,
Paul A. Welling,
Jill W. Verlander,
I. David Weiner,
Previous studies have shown that glutamine administration simultaneously increases ammonia excretion and decreases K+ excretion. The current studies determined whether increased ammonia metabolism is necessary for the normal kaliuretic response to hypokalemia.
We used NBCe1-A KO mice, which have decreased ammonia response to metabolic acidosis, and WT littermates. We determined whether NBCe1-A KO blocked the ammonia response to hypokalemia and whether this response was necessary for normal changes in K+ excretion. Lastly, we incubated tissue slices with defined solutions to determine direct effects of ammonia on NCC phosphorylation.
In WT mice exposed to a K+-free diet for 4 days, as compared to mice provided K+-control diet, there was increased ammonia excretion, increased expression of cortical ammoniagenic enzymes, PDG and PEPCK, and decreased expression of the ammonia recycling enzyme, glutamine synthetase. In KO mice each of these responses was blunted significantly. NBCe1-A KO mice have a genetic mutation affecting only cortical proximal tubule segments, which is not thought to regulate K+ excretion, yet when exposed to a K+-free diet developed a significantly lower serum K+, measured on day 4, and they excreted significantly more urinary K+ on each day than did WT littermates. Distal nephron K+ transporter, ROMK, BK channel, and H+-K+-ATPase α1 and α2, expression did not differ detectably between hypokalemic WT and KO mice. ENaC α, β and γ expression increased with K+-free diet similarly in WT and KO mice. NCC phosphorylation, which has a key role in the renal response to hypokalemia, however, was significantly less in hypokalemic KO than in hypokalemic WT mice. Ex vivo incubation of kidney slices for 1 hour in defined solutions showed that decreased extracellular K+ increased phospho-NCC expression over the tested range of 2-8 mM K+. Addition of ammonia, 2 mM, also increased phospho-NCC expression. Total NCC expression was not altered by changes in extracellular K+ or by ammonia addition.
The renal kaliuretic response to dietary K+-deficiency-induced hypokalemia requires an NBCe1-A-dependent increase in cortical proximal tubule segments ammoniagenesis, which then leads to an ammonia-dependent stimulation of NCC phosphorylation that is necessary for normal K+ conservation.
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