Skip to main content
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
. 1988 Nov;85(21):8345–8349. doi: 10.1073/pnas.85.21.8345

Cytoplasmic pH determines K+ conductance in fused renal epithelial cells.

H Oberleithner 1, U Kersting 1, M Hunter 1
PMCID: PMC282426  PMID: 2460867

Abstract

The mineralocorticoid hormone aldosterone maintains acid-base balance and K+ homeostasis by regulating H+ and K+ secretory mechanisms in kidney epithelial cells. We have shown recently in the amphibian distal nephron that aldosterone activates a Na+/H+ exchange system in the luminal cell membrane, thus leading to transepithelial H+ secretion and cytoplasmic alkalinization. Since H+ secretory fluxes were paralleled by K+ secretion, it was postulated that the hormone-induced increase of intracellular pH activates the luminally located K+ channels. In "giant" cells fused from individual cells of the distal nephron, we measured simultaneously cytoplasmic pH and cell membrane K+ conductance during acidification of the cell cytoplasm. The experiments show that cell membrane K+ conductance is half-maximal at an intracellular pH of 7.42 and that a positive cooperative interaction exists between K+-channel proteins and H+ (Hill coefficient = 6.5). Moreover, the cellular K+ conductance is most sensitive to cytoplasmic pH in the range modified by aldosterone. This supports the hypothesis that intracellular H+ activity, regulated by the Na+/H+ exchanger, serves as the signal to couple aldosterone-induced K+ secretory flux to H+ secretion in renal tubules.

Full text

PDF

Images in this article

Selected References

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

  1. Baulieu E. E., Godeau F., Schorderet M., Schorderet-Slatkine S. Steroid-induced meiotic division in Xenopus laevis oocytes: surface and calcium. Nature. 1978 Oct 19;275(5681):593–598. doi: 10.1038/275593a0. [DOI] [PubMed] [Google Scholar]
  2. Cook D. L., Ikeuchi M., Fujimoto W. Y. Lowering of pHi inhibits Ca2+-activated K+ channels in pancreatic B-cells. Nature. 1984 Sep 20;311(5983):269–271. doi: 10.1038/311269a0. [DOI] [PubMed] [Google Scholar]
  3. Fanestil D. D., Park C. S. Steroid hormones and the kidney. Annu Rev Physiol. 1981;43:637–649. doi: 10.1146/annurev.ph.43.030181.003225. [DOI] [PubMed] [Google Scholar]
  4. Field M. J., Stanton B. A., Giebisch G. H. Differential acute effects of aldosterone, dexamethasone, and hyperkalemia on distal tubular potassium secretion in the rat kidney. J Clin Invest. 1984 Nov;74(5):1792–1802. doi: 10.1172/JCI111598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Garty H., Asher C., Yeger O. Direct inhibition of epithelial Na+ channels by a pH-dependent interaction with calcium, and by other divalent ions. J Membr Biol. 1987;95(2):151–162. doi: 10.1007/BF01869160. [DOI] [PubMed] [Google Scholar]
  6. Greger R. Ion transport mechanisms in thick ascending limb of Henle's loop of mammalian nephron. Physiol Rev. 1985 Jul;65(3):760–797. doi: 10.1152/physrev.1985.65.3.760. [DOI] [PubMed] [Google Scholar]
  7. Grinstein S., Cohen S. Cytoplasmic [Ca2+] and intracellular pH in lymphocytes. Role of membrane potential and volume-activated Na+/H+ exchange. J Gen Physiol. 1987 Feb;89(2):185–213. doi: 10.1085/jgp.89.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hunter M., Giebisch G. Multi-barrelled K channels in renal tubules. Nature. 1987 Jun 11;327(6122):522–524. doi: 10.1038/327522a0. [DOI] [PubMed] [Google Scholar]
  9. Hunter M., Kawahara K., Giebisch G. Potassium channels along the nephron. Fed Proc. 1986 Nov;45(12):2723–2726. [PubMed] [Google Scholar]
  10. Koeppen B. M., Biagi B. A., Giebisch G. H. Intracellular microelectrode characterization of the rabbit cortical collecting duct. Am J Physiol. 1983 Jan;244(1):F35–F47. doi: 10.1152/ajprenal.1983.244.1.F35. [DOI] [PubMed] [Google Scholar]
  11. Oberleithner H., Guggino W., Giebisch G. Mechanism of distal tubular chloride transport in Amphiuma kidney. Am J Physiol. 1982 Apr;242(4):F331–F339. doi: 10.1152/ajprenal.1982.242.4.F331. [DOI] [PubMed] [Google Scholar]
  12. Oberleithner H., Weigt M., Westphale H. J., Wang W. Aldosterone activates Na+/H+ exchange and raises cytoplasmic pH in target cells of the amphibian kidney. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1464–1468. doi: 10.1073/pnas.84.5.1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rosario L. M., Rojas E. Modulation of K+ conductance by intracellular pH in pancreatic beta-cells. FEBS Lett. 1986 May 5;200(1):203–209. doi: 10.1016/0014-5793(86)80539-7. [DOI] [PubMed] [Google Scholar]
  14. Schwartz G. J., Burg M. B. Mineralocorticoid effects on cation transport by cortical collecting tubules in vitro. Am J Physiol. 1978 Dec;235(6):F576–F585. doi: 10.1152/ajprenal.1978.235.6.F576. [DOI] [PubMed] [Google Scholar]
  15. Steinmetz P. R. Cellular mechanisms of urinary acidification. Physiol Rev. 1974 Oct;54(4):890–956. doi: 10.1152/physrev.1974.54.4.890. [DOI] [PubMed] [Google Scholar]
  16. Wanke E., Carbone E., Testa P. L. K+ conductance modified by a titratable group accessible to protons from the intracellular side of the squid axon membrane. Biophys J. 1979 May;26(2):319–324. doi: 10.1016/S0006-3495(79)85251-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Weigt M., Dietl P., Silbernagl S., Oberleithner H. Activation of luminal Na+/H+ exchange in distal nephron of frog kidney. An early response to aldosterone. Pflugers Arch. 1987 May;408(6):609–614. doi: 10.1007/BF00581163. [DOI] [PubMed] [Google Scholar]
  18. Wiederholt M., Schoormans W., Fischer F., Behn C. Mechanism of action of aldosterone on potassium transfer in the rat kidney. Pflugers Arch. 1973 Dec 12;345(2):159–178. doi: 10.1007/BF00585838. [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