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Abstract: TH-PO312

NBCe1-B/C Knockout Mice Exhibit an Impaired Respiratory Response to Metabolic Acidosis Resulting in Increased Ammonia Excretion

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic


  • Brady, Clayton, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, United States
  • Parker, Mark, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, United States

Sodium-bicarbonate cotransporter variants NBCe1-B and NBCe1-C (NBCe1-B/C) are expressed in the brainstem while variants NBCe1-A and NBCe1-B are expressed in the proximal tubule. NBCe1-A is the primary renal variant and is important to the kidney response to metabolic acidosis (MAc). Less understood is the role of NBCe1-B/C, but they are thought to play a role in both the respiratory and renal responses to MAc. We tested this hypothesis in NBCe1-B/C knockout (KOb/c) mice.


We validated an NBCe1-B/C specific antibody and used it to confirm the presence/absence of NBCe1-B in the kidney and NBCe1-B/C in the brainstem of WT and KOb/c mice. MAc was induced by adding 0.5% sucrose + 0.28M NH4Cl to drinking water. The abundance response of kidney NBCe1-B to MAc was quantified in WT mice by western blot. To assess the effect of MAc on acid-base status, WT and KOb/c mice were subjected to control (0.5% sucrose in drinking water) or MAc conditions for 1-3 days followed by cardiac puncture and blood-gas/electrolyte analysis. 24-hour urine collections were assessed for ammonia excretion, titratable acid (TA) excretion, and pH. The respiratory response was assessed using whole-body plethysmography, with WT and KOb/c mice assessed each day of a 3-day MAc-challenge.


After 3-days of MAc, NBCe1-B kidney abundance was 3.6x that of controls in WT mice, supporting evidence of a role for NBCe1-B in the kidney during MAc. Surprisingly, however, KOb/c mice had a greater recovery in plasma [HCO3-] and higher pCO2 levels, but a similar recovery in plasma pH to WT mice. This was associated with a greater increase in ammonia excretion in KOb/c males but not females, whereas there were no differences in changes in TA excretion or urine pH between WT and KOb/c mice. In regards to the respiratory response, over the 3-day MAc challenge WT mice exhibited a maximum increase in minute volume of 10% whereas in KOb/c mice minute volume did not significantly change.


The impaired respiratory response to MAc in KOb/c mice leads to elevated ammonia excretion and a greater recovery in plasma [HCO3-]. We suggest this is because, although normally the respiratory response to MAc lowers pCO2 in order to help maintain plasma pH, this decrease in pCO2 also has an inhibitory effect on renal ammoniagenesis.


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