Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Aug;86(16):6431–6435. doi: 10.1073/pnas.86.16.6431

Coordinated regulation of intracellular K+ in the proximal tubule: Ba2+ blockade down-regulates the Na+,K+-ATPase and up-regulates two K+ permeability pathways.

B C Kone 1, H R Brady 1, S R Gullans 1
PMCID: PMC297854  PMID: 2548216

Abstract

To avoid large changes in cell K+ content and volume during variations in Na+,K+-ATPase activity, Na+-transporting epithelia must adjust the rate of K+ exit through passive permeability pathways. Recent studies have shown that a variety of passive K+ transport mechanisms may coexist within a cell and may be functionally linked to the activity of the Na+,K+-ATPase. In this study, we have identified three distinct pathways for passive K+ transport that act in concert with the Na+,K+-ATPase to maintain intracellular K+ homeostasis in the proximal tubule. Under control conditions, the total K+ leak of the tubules consisted of discrete Ba2+-sensitive (approximately 65%), quinine-sensitive (approximately 20%), and furosemide-sensitive (approximately 10%) pathways. Following inhibition of the principal K+ leak pathway with Ba2+, the tubules adaptively restored cell K+ content to normal levels. This recovery of cell K+ content was inhibited, in an additive manner, by quinine and furosemide. Following adaptation to Ba2+, the tubules exhibited a 30% reduction in Na+-K+ pump rate coupled with an increase in K+ leak by means of the quinine-sensitive (approximately 70%) and furosemide-sensitive (approximately 280%) pathways. Thus, the proximal tubule maintains intracellular K+ homeostasis by the coordinated modulation of multiple K+ transport pathways. Furthermore, these results suggest that, like Ba2+, other inhibitors of K+ conductance will cause compensatory changes in both the Na+-K+ pump and alternative pathways for passive K+ transport.

Full text

PDF
6431

Selected References

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

  1. Avison M. J., Gullans S. R., Ogino T., Giebisch G. Na+ and K+ fluxes stimulated by Na+-coupled glucose transport: evidence for a Ba2+-insensitive K+ efflux pathway in rabbit proximal tubules. J Membr Biol. 1988 Nov;105(3):197–205. doi: 10.1007/BF01870997. [DOI] [PubMed] [Google Scholar]
  2. Avison M. J., Gullans S. R., Ogino T., Giebisch G., Shulman R. G. Measurement of Na+-K+ coupling ratio of Na+-K+-ATPase in rabbit proximal tubules. Am J Physiol. 1987 Jul;253(1 Pt 1):C126–C136. doi: 10.1152/ajpcell.1987.253.1.C126. [DOI] [PubMed] [Google Scholar]
  3. Bello-Reuss E. Electrical properties of the basolateral membrane of the straight portion of the rabbit proximal renal tubule. J Physiol. 1982 May;326:49–63. doi: 10.1113/jphysiol.1982.sp014176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Biagi B., Sohtell M., Giebisch G. Intracellular potassium activity in the rabbit proximal straight tubule. Am J Physiol. 1981 Dec;241(6):F677–F686. doi: 10.1152/ajprenal.1981.241.6.F677. [DOI] [PubMed] [Google Scholar]
  5. Brady H. R., Kone B. C., Gullans S. R. Extracellular Na+ electrode for monitoring net Na+ flux in cell suspensions. Am J Physiol. 1989 May;256(5 Pt 1):C1105–C1110. doi: 10.1152/ajpcell.1989.256.5.C1105. [DOI] [PubMed] [Google Scholar]
  6. Cox T. C., Helman S. I. Na+ and K+ transport at basolateral membranes of epithelial cells. II. K+ efflux and stoichiometry of the Na,K-ATPase. J Gen Physiol. 1986 Mar;87(3):485–502. doi: 10.1085/jgp.87.3.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eveloff J., Warnock D. G. K-Cl transport systems in rabbit renal basolateral membrane vesicles. Am J Physiol. 1987 May;252(5 Pt 2):F883–F889. doi: 10.1152/ajprenal.1987.252.5.F883. [DOI] [PubMed] [Google Scholar]
  8. Grasset E., Gunter-Smith P., Schultz S. G. Effects of Na-coupled alanine transport on intracellular K activities and the K conductance of the basolateral membranes of Necturus small intestine. J Membr Biol. 1983;71(1-2):89–94. doi: 10.1007/BF01870677. [DOI] [PubMed] [Google Scholar]
  9. Gullans S. R., Avison M. J., Ogino T., Giebisch G., Shulman R. G. NMR measurements of intracellular sodium in the rabbit proximal tubule. Am J Physiol. 1985 Jul;249(1 Pt 2):F160–F168. doi: 10.1152/ajprenal.1985.249.1.F160. [DOI] [PubMed] [Google Scholar]
  10. Gunter-Smith P. J., Grasset E., Schultz S. G. Sodium-coupled amino acid and sugar transport by Necturus small intestine. An equivalent electrical circuit analysis of a rheogenic co-transport system. J Membr Biol. 1982;66(1):25–39. doi: 10.1007/BF01868479. [DOI] [PubMed] [Google Scholar]
  11. Gögelein H., Greger R. Properties of single K+ channels in the basolateral membrane of rabbit proximal straight tubules. Pflugers Arch. 1987 Oct;410(3):288–295. doi: 10.1007/BF00580279. [DOI] [PubMed] [Google Scholar]
  12. Gögelein H., Greger R. Single channel recordings from basolateral and apical membranes of renal proximal tubules. Pflugers Arch. 1984 Aug;401(4):424–426. doi: 10.1007/BF00584348. [DOI] [PubMed] [Google Scholar]
  13. Hoffmann E. K., Simonsen L. O., Lambert I. H. Volume-induced increase of K+ and Cl- permeabilities in Ehrlich ascites tumor cells. Role of internal Ca2+. J Membr Biol. 1984;78(3):211–222. doi: 10.1007/BF01925969. [DOI] [PubMed] [Google Scholar]
  14. Kirk K. L., DiBona D. R., Schafer J. A. Regulatory volume decrease in perfused proximal nephron: evidence for a dumping of cell K+. Am J Physiol. 1987 May;252(5 Pt 2):F933–F942. doi: 10.1152/ajprenal.1987.252.5.F933. [DOI] [PubMed] [Google Scholar]
  15. Kone B. C., Kaleta M., Gullans S. R. Silver ion (Ag+)-induced increases in cell membrane K+ and Na+ permeability in the renal proximal tubule: reversal by thiol reagents. J Membr Biol. 1988 Apr;102(1):11–19. doi: 10.1007/BF01875349. [DOI] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Lang F., Messner G., Rehwald W. Electrophysiology of sodium-coupled transport in proximal renal tubules. Am J Physiol. 1986 Jun;250(6 Pt 2):F953–F962. doi: 10.1152/ajprenal.1986.250.6.F953. [DOI] [PubMed] [Google Scholar]
  18. Larson M., Spring K. R. Volume regulation by Necturus gallbladder: basolateral KCl exit. J Membr Biol. 1984;81(3):219–232. doi: 10.1007/BF01868715. [DOI] [PubMed] [Google Scholar]
  19. Matsumura Y., Cohen B., Guggino W. B., Giebisch G. Regulation of the basolateral potassium conductance of the Necturus proximal tubule. J Membr Biol. 1984;79(2):153–161. doi: 10.1007/BF01872119. [DOI] [PubMed] [Google Scholar]
  20. Messner G., Wang W., Paulmichl M., Oberleithner H., Lang F. Ouabain decreases apparent potassium-conductance in proximal tubules of the amphibian kidney. Pflugers Arch. 1985 May;404(2):131–137. doi: 10.1007/BF00585408. [DOI] [PubMed] [Google Scholar]
  21. Parent L., Cardinal J., Sauvé R. Single-channel analysis of a K channel at basolateral membrane of rabbit proximal convoluted tubule. Am J Physiol. 1988 Jan;254(1 Pt 2):F105–F113. doi: 10.1152/ajprenal.1988.254.1.F105. [DOI] [PubMed] [Google Scholar]
  22. Richards N. W., Dawson D. C. Single potassium channels blocked by lidocaine and quinidine in isolated turtle colon epithelial cells. Am J Physiol. 1986 Jul;251(1 Pt 1):C85–C89. doi: 10.1152/ajpcell.1986.251.1.C85. [DOI] [PubMed] [Google Scholar]
  23. Sasaki S., Ishibashi K., Yoshiyama N., Shiigai T. KCl co-transport across the basolateral membrane of rabbit renal proximal straight tubules. J Clin Invest. 1988 Jan;81(1):194–199. doi: 10.1172/JCI113294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schultz S. G. Homocellular regulatory mechanisms in sodium-transporting epithelia: avoidance of extinction by "flush-through". Am J Physiol. 1981 Dec;241(6):F579–F590. doi: 10.1152/ajprenal.1981.241.6.F579. [DOI] [PubMed] [Google Scholar]
  25. Soltoff S. P., Mandel L. J. Active ion transport in the renal proximal tubule. I. Transport and metabolic studies. J Gen Physiol. 1984 Oct;84(4):601–622. doi: 10.1085/jgp.84.4.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Soltoff S. P., Mandel L. J. Potassium transport in the rabbit renal proximal tubule: effects of barium, ouabain, valinomycin, and other ionophores. J Membr Biol. 1986;94(2):153–161. doi: 10.1007/BF01871195. [DOI] [PubMed] [Google Scholar]
  27. TOSTESON D. C., HOFFMAN J. F. Regulation of cell volume by active cation transport in high and low potassium sheep red cells. J Gen Physiol. 1960 Sep;44:169–194. doi: 10.1085/jgp.44.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Völkl H., Greger R., Lang F. Potassium conductance in straight proximal tubule cells of the mouse. Effect of barium, verapamil and quinidine. Biochim Biophys Acta. 1987 Jun 30;900(2):275–281. doi: 10.1016/0005-2736(87)90342-7. [DOI] [PubMed] [Google Scholar]
  29. Welling P. A., Linshaw M. A. Importance of anion in hypotonic volume regulation of rabbit proximal straight tubule. Am J Physiol. 1988 Nov;255(5 Pt 2):F853–F860. doi: 10.1152/ajprenal.1988.255.5.F853. [DOI] [PubMed] [Google Scholar]
  30. Welling P. A., Linshaw M. A., Sullivan L. P. Effect of barium on cell volume regulation in rabbit proximal straight tubules. Am J Physiol. 1985 Jul;249(1 Pt 2):F20–F27. doi: 10.1152/ajprenal.1985.249.1.F20. [DOI] [PubMed] [Google Scholar]
  31. White J. F. Intracellular potassium activities in Amphiuma small intestine. Am J Physiol. 1976 Oct;231(4):1214–1219. doi: 10.1152/ajplegacy.1976.231.4.1214. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES