NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis
The sodium-bicarbonate cotransporter (NBCe1) has three primary variants: NBCe1-A, -B and -C. NBCe1-A is expressed in renal proximal tubules in the cortical labyrinth, where it is essential for reclaiming filtered bicarbonate, such that NBCe1-A knockout mice are congenitally acidemic. NBCe1-B and -C...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1201034/full |
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| author | Clayton T. Brady Aniko Marshall Chen Zhang Chen Zhang Mark D. Parker Mark D. Parker |
| author_facet | Clayton T. Brady Aniko Marshall Chen Zhang Chen Zhang Mark D. Parker Mark D. Parker |
| author_sort | Clayton T. Brady |
| collection | DOAJ |
| description | The sodium-bicarbonate cotransporter (NBCe1) has three primary variants: NBCe1-A, -B and -C. NBCe1-A is expressed in renal proximal tubules in the cortical labyrinth, where it is essential for reclaiming filtered bicarbonate, such that NBCe1-A knockout mice are congenitally acidemic. NBCe1-B and -C variants are expressed in chemosensitive regions of the brainstem, while NBCe1-B is also expressed in renal proximal tubules located in the outer medulla. Although mice lacking NBCe1-B/C (KOb/c) exhibit a normal plasma pH at baseline, the distribution of NBCe1-B/C indicates that these variants could play a role in both the rapid respiratory and slower renal responses to metabolic acidosis (MAc). Therefore, in this study we used an integrative physiologic approach to investigate the response of KOb/c mice to MAc. By means of unanesthetized whole-body plethysmography and blood-gas analysis, we demonstrate that the respiratory response to MAc (increase in minute volume, decrease in pCO2) is impaired in KOb/c mice leading to a greater severity of acidemia after 1 day of MAc. Despite this respiratory impairment, the recovery of plasma pH after 3-days of MAc remained intact in KOb/c mice. Using data gathered from mice housed in metabolic cages we demonstrate a greater elevation of renal ammonium excretion and greater downregulation of the ammonia recycling enzyme glutamine synthetase in KOb/c mice on day 2 of MAc, consistent with greater renal acid-excretion. We conclude that KOb/c mice are ultimately able to defend plasma pH during MAc, but that the integrated response is disturbed such that the burden of work shifts from the respiratory system to the kidneys, delaying the recovery of pH. |
| first_indexed | 2024-03-13T04:41:32Z |
| format | Article |
| id | doaj.art-88ab2e4eea484109834928cf6c1d73b9 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-03-13T04:41:32Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-88ab2e4eea484109834928cf6c1d73b92023-06-19T05:38:11ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-06-011410.3389/fphys.2023.12010341201034NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosisClayton T. Brady0Aniko Marshall1Chen Zhang2Chen Zhang3Mark D. Parker4Mark D. Parker5Jacobs School of Medicine and Biomedical Sciences, Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, NY, United StatesJacobs School of Medicine and Biomedical Sciences, Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, NY, United StatesJacobs School of Medicine and Biomedical Sciences, Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, NY, United StatesDepartment of Biological Sciences, The State University of New York: The University at Buffalo, Buffalo, NY, United StatesJacobs School of Medicine and Biomedical Sciences, Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, NY, United StatesJacobs School of Medicine and Biomedical Sciences, Department of Ophthalmology, The State University of New York: The University at Buffalo, Buffalo, NY, United StatesThe sodium-bicarbonate cotransporter (NBCe1) has three primary variants: NBCe1-A, -B and -C. NBCe1-A is expressed in renal proximal tubules in the cortical labyrinth, where it is essential for reclaiming filtered bicarbonate, such that NBCe1-A knockout mice are congenitally acidemic. NBCe1-B and -C variants are expressed in chemosensitive regions of the brainstem, while NBCe1-B is also expressed in renal proximal tubules located in the outer medulla. Although mice lacking NBCe1-B/C (KOb/c) exhibit a normal plasma pH at baseline, the distribution of NBCe1-B/C indicates that these variants could play a role in both the rapid respiratory and slower renal responses to metabolic acidosis (MAc). Therefore, in this study we used an integrative physiologic approach to investigate the response of KOb/c mice to MAc. By means of unanesthetized whole-body plethysmography and blood-gas analysis, we demonstrate that the respiratory response to MAc (increase in minute volume, decrease in pCO2) is impaired in KOb/c mice leading to a greater severity of acidemia after 1 day of MAc. Despite this respiratory impairment, the recovery of plasma pH after 3-days of MAc remained intact in KOb/c mice. Using data gathered from mice housed in metabolic cages we demonstrate a greater elevation of renal ammonium excretion and greater downregulation of the ammonia recycling enzyme glutamine synthetase in KOb/c mice on day 2 of MAc, consistent with greater renal acid-excretion. We conclude that KOb/c mice are ultimately able to defend plasma pH during MAc, but that the integrated response is disturbed such that the burden of work shifts from the respiratory system to the kidneys, delaying the recovery of pH.https://www.frontiersin.org/articles/10.3389/fphys.2023.1201034/fullNBCe1acid-baseacidosisbicarbonatetransportkidney |
| spellingShingle | Clayton T. Brady Aniko Marshall Chen Zhang Chen Zhang Mark D. Parker Mark D. Parker NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis Frontiers in Physiology NBCe1 acid-base acidosis bicarbonate transport kidney |
| title | NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis |
| title_full | NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis |
| title_fullStr | NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis |
| title_full_unstemmed | NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis |
| title_short | NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis |
| title_sort | nbce1 b c knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis |
| topic | NBCe1 acid-base acidosis bicarbonate transport kidney |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1201034/full |
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