Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Jul;90(1):211–218. doi: 10.1172/JCI115838

Effect of in vitro metabolic acidosis on luminal Na+/H+ exchange and basolateral Na+:HCO3- cotransport in rabbit kidney proximal tubules.

M Soleimani 1, G L Bizal 1, T D McKinney 1, Y J Hattabaugh 1
PMCID: PMC443083  PMID: 1321842

Abstract

The aim of this study was to evaluate the role of the kidney in mediating the signals involved in adaptive changes in luminal Na+/H+ exchange and basolateral Na+:HCO3- cotransport systems in metabolic acidosis. Proximal tubular suspensions were prepared from rabbit kidney cortex and incubated in acidic (A) or control (C) media (pH 6.9 vs 7.4, 5% CO2) for 2 h. Brush border membrane (BBM) and basolateral membrane (BLM) vesicles were isolated from the tubular suspensions and studied for the activity of Na+/H+ exchange and Na+:HCO3- cotransport. Influx of 1 mM 22Na at 10 s (pH6 7.5, pH(i) 6.0) into BBM vesicles was 68% higher in group A compared to group C. The increment in Na+ influx in the group A was amiloride sensitive, suggesting that Na+/H+ exchange was responsible for the observed differences. Kinetic analysis of Na+ influx showed a Km of 8.1 mM in C vs 9.2 in A and Vmax of 31 nmol/mg protein per min in group C vs 57 in A. Influx of 1 mM 22Na at 10 s (pH0 7.5, pH(i) 6.0, 20% CO2, 80% N2) into BLM vesicles was 83% higher in the group A compared to C. The HCO3-dependent increment in 22Na uptake in group A was 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid sensitive, suggesting that Na+:HCO3- cotransport accounted for the observed differences. Kinetic analysis of Na+ influx showed a Km of 11.4 mM in C vs 13.6 in A and Vmax of 35 nmol/mg protein per min in C vs 64 in A. The presence of cyclohexamide during incubation in A medium had no effect on the increments in 22Na uptake in group A. We conclude that the adaptive increase in luminal Na+/H+ exchange and basolateral Na+:HCO3- cotransport systems in metabolic acidosis is acute and mediated via direct signal(s) at the level of renal tubule.

Full text

PDF
211

Images in this article

213Image
on p.213
214Image
on p.214

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akiba T., Rocco V. K., Warnock D. G. Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis. J Clin Invest. 1987 Aug;80(2):308–315. doi: 10.1172/JCI113074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alpern R. J. Cell mechanisms of proximal tubule acidification. Physiol Rev. 1990 Jan;70(1):79–114. doi: 10.1152/physrev.1990.70.1.79. [DOI] [PubMed] [Google Scholar]
  3. Aronson P. S. Mechanisms of active H+ secretion in the proximal tubule. Am J Physiol. 1983 Dec;245(6):F647–F659. doi: 10.1152/ajprenal.1983.245.6.F647. [DOI] [PubMed] [Google Scholar]
  4. Aronson P. S., Soleimani M., Grassl S. M. Properties of the renal Na(+)-HCO3- cotransporter. Semin Nephrol. 1991 Jan;11(1):28–36. [PubMed] [Google Scholar]
  5. Astion M. L., Obaid A. L., Orkand R. K. Effects of barium and bicarbonate on glial cells of Necturus optic nerve. Studies with microelectrodes and voltage-sensitive dyes. J Gen Physiol. 1989 Apr;93(4):731–744. doi: 10.1085/jgp.93.4.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boron W. F., Boulpaep E. L. The electrogenic Na/HCO3 cotransporter. Kidney Int. 1989 Sep;36(3):392–402. doi: 10.1038/ki.1989.208. [DOI] [PubMed] [Google Scholar]
  7. Cogan M. G., Alpern R. J. Regulation of proximal bicarbonate reabsorption. Am J Physiol. 1984 Sep;247(3 Pt 2):F387–F395. doi: 10.1152/ajprenal.1984.247.3.F387. [DOI] [PubMed] [Google Scholar]
  8. Curci S., Debellis L., Frömter E. Evidence for rheogenic sodium bicarbonate cotransport in the basolateral membrane of oxyntic cells of frog gastric fundus. Pflugers Arch. 1987 May;408(5):497–504. doi: 10.1007/BF00585075. [DOI] [PubMed] [Google Scholar]
  9. Evers C., Haase W., Murer H., Kinne R. Properties of brush border vesicles isolated from rat kidney cortex by calcium precipitation. Membr Biochem. 1978;1(3-4):203–219. doi: 10.3109/09687687809063848. [DOI] [PubMed] [Google Scholar]
  10. Fitz J. G., Persico M., Scharschmidt B. F. Electrophysiological evidence for Na+-coupled bicarbonate transport in cultured rat hepatocytes. Am J Physiol. 1989 Mar;256(3 Pt 1):G491–G500. doi: 10.1152/ajpgi.1989.256.3.G491. [DOI] [PubMed] [Google Scholar]
  11. Grassl S. M., Aronson P. S. Na+/HCO3-co-transport in basolateral membrane vesicles isolated from rabbit renal cortex. J Biol Chem. 1986 Jul 5;261(19):8778–8783. [PubMed] [Google Scholar]
  12. Grinstein S., Rothstein A. Mechanisms of regulation of the Na+/H+ exchanger. J Membr Biol. 1986;90(1):1–12. doi: 10.1007/BF01869680. [DOI] [PubMed] [Google Scholar]
  13. Horie S., Moe O., Tejedor A., Alpern R. J. Preincubation in acid medium increases Na/H antiporter activity in cultured renal proximal tubule cells. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4742–4745. doi: 10.1073/pnas.87.12.4742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ives H. E. Proton/hydroxyl permeability of proximal tubule brush border vesicles. Am J Physiol. 1985 Jan;248(1 Pt 2):F78–F86. doi: 10.1152/ajprenal.1985.248.1.F78. [DOI] [PubMed] [Google Scholar]
  15. Ives H. E., Verkman A. S. Effects of membrane fluidizing agents on renal brush border proton permeability. Am J Physiol. 1985 Dec;249(6 Pt 2):F933–F940. doi: 10.1152/ajprenal.1985.249.6.F933. [DOI] [PubMed] [Google Scholar]
  16. Jentsch T. J., Stahlknecht T. R., Hollwede H., Fischer D. G., Keller S. K., Wiederholt M. A bicarbonate-dependent process inhibitable by disulfonic stilbenes and a Na+/H+ exchange mediate 22Na+ uptake into cultured bovine corneal endothelium. J Biol Chem. 1985 Jan 25;260(2):795–801. [PubMed] [Google Scholar]
  17. Kahn A. M., Dolson G. M., Hise M. K., Bennett S. C., Weinman E. J. Parathyroid hormone and dibutyryl cAMP inhibit Na+/H+ exchange in renal brush border vesicles. Am J Physiol. 1985 Feb;248(2 Pt 2):F212–F218. doi: 10.1152/ajprenal.1985.248.2.F212. [DOI] [PubMed] [Google Scholar]
  18. Kleinman J. G., Brown W. W., Ware R. A., Schwartz J. H. Cell pH and acid transport in renal cortical tissue. Am J Physiol. 1980 Nov;239(5):F440–F444. doi: 10.1152/ajprenal.1980.239.5.F440. [DOI] [PubMed] [Google Scholar]
  19. Krapf R. Basolateral membrane H/OH/HCO3 transport in the rat cortical thick ascending limb. Evidence for an electrogenic Na/HCO3 cotransporter in parallel with a Na/H antiporter. J Clin Invest. 1988 Jul;82(1):234–241. doi: 10.1172/JCI113576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kunau R. T., Jr, Hart J. I., Walker K. A. Effect of metabolic acidosis on proximal tubular total CO2 absorption. Am J Physiol. 1985 Jul;249(1 Pt 2):F62–F68. doi: 10.1152/ajprenal.1985.249.1.F62. [DOI] [PubMed] [Google Scholar]
  21. Levi M., Jameson D. M., van der Meer B. W. Role of BBM lipid composition and fluidity in impaired renal Pi transport in aged rat. Am J Physiol. 1989 Jan;256(1 Pt 2):F85–F94. doi: 10.1152/ajprenal.1989.256.1.F85. [DOI] [PubMed] [Google Scholar]
  22. Levine B. S., Knibloe K. A., Golchini K., Hashimoto S., Kurtz I. Renal adaptation to dietary phosphate deprivation: role of proximal tubule brush-border membrane fluidity. Am J Physiol. 1991 May;260(5 Pt 2):F613–F618. doi: 10.1152/ajprenal.1991.260.5.F613. [DOI] [PubMed] [Google Scholar]
  23. Madias N. E., Zelman S. J. The renal response to chronic mineral acid feeding: a re-examination of the role of systemic pH. Kidney Int. 1986 Mar;29(3):667–674. doi: 10.1038/ki.1986.50. [DOI] [PubMed] [Google Scholar]
  24. Mahnensmith R. L., Aronson P. S. The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res. 1985 Jun;56(6):773–788. doi: 10.1161/01.res.56.6.773. [DOI] [PubMed] [Google Scholar]
  25. McKinney T. D., Kunnemann M. E. Procainamide transport in rabbit renal cortical brush border membrane vesicles. Am J Physiol. 1985 Oct;249(4 Pt 2):F532–F541. doi: 10.1152/ajprenal.1985.249.4.F532. [DOI] [PubMed] [Google Scholar]
  26. Moe O. W., Miller R. T., Horie S., Cano A., Preisig P. A., Alpern R. J. Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts. J Clin Invest. 1991 Nov;88(5):1703–1708. doi: 10.1172/JCI115487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Preisig P. A., Alpern R. J. Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule. J Clin Invest. 1988 Oct;82(4):1445–1453. doi: 10.1172/JCI113750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schwartz G. J., Al-Awqati Q. Carbon dioxide causes exocytosis of vesicles containing H+ pumps in isolated perfused proximal and collecting tubules. J Clin Invest. 1985 May;75(5):1638–1644. doi: 10.1172/JCI111871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Soleimani M., Aronson P. S. Ionic mechanism of Na+-HCO3- cotransport in rabbit renal basolateral membrane vesicles. J Biol Chem. 1989 Nov 5;264(31):18302–18308. [PubMed] [Google Scholar]
  30. Soleimani M., Bergman J. A., Hosford M. A., McKinney T. D. Potassium depletion increases luminal Na+/H+ exchange and basolateral Na+:CO3=:HCO3- cotransport in rat renal cortex. J Clin Invest. 1990 Oct;86(4):1076–1083. doi: 10.1172/JCI114810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Soleimani M., Grassi S. M., Aronson P. S. Stoichiometry of Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex. J Clin Invest. 1987 Apr;79(4):1276–1280. doi: 10.1172/JCI112948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Soleimani M., Lesoine G. A., Bergman J. A., Aronson P. S. Cation specificity and modes of the Na+:CO3(2-):HCO3- cotransporter in renal basolateral membrane vesicles. J Biol Chem. 1991 May 15;266(14):8706–8710. [PubMed] [Google Scholar]
  33. Struyvenberg A., Morrison R. B., Relman A. S. Acid-base behavior of separated canine renal tubule cells. Am J Physiol. 1968 May;214(5):1155–1162. doi: 10.1152/ajplegacy.1968.214.5.1155. [DOI] [PubMed] [Google Scholar]
  34. Tsai C. J., Ives H. E., Alpern R. J., Yee V. J., Warnock D. G., Rector F. C., Jr Increased Vmax for Na+/H+ antiporter activity in proximal tubule brush border vesicles from rabbits with metabolic acidosis. Am J Physiol. 1984 Aug;247(2 Pt 2):F339–F343. doi: 10.1152/ajprenal.1984.247.2.F339. [DOI] [PubMed] [Google Scholar]
  35. Yoshitomi K., Burckhardt B. C., Frömter E. Rheogenic sodium-bicarbonate cotransport in the peritubular cell membrane of rat renal proximal tubule. Pflugers Arch. 1985 Dec;405(4):360–366. doi: 10.1007/BF00595689. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES