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
. 1982 Mar;79(5):1453–1456. doi: 10.1073/pnas.79.5.1453

Membrane potential changes induced by the ouabain-like compound extracted from mammalian brain.

D Lichtstein, S Samuelov
PMCID: PMC345991  PMID: 6280183

Abstract

The electrical membrane potential (delta psi) of chicken embryo fibroblasts in tissue culture was determined to be -30.5 +/- 2.9 mV as measured by distribution of the lipophilic [3H]tetraphenylphosphonium cation (Ph4P+). Stimulation of the electrogenic activity of the Na+,K+-ATPase by the ionophore monensin induces a hyperpolarization of approximately 47 mV and a new delta psi of -77.3 +/- 5.7 mV. The effects of the cardiac glycoside ouabain and an "ouabain-like compound" (OLC), which was extracted and partially purified from sheep brain, were contrasted using both the resting and hyperpolarized fibroblasts. Addition of OLC or ouabain to the incubation medium for short periods of time does not alter the cells' resting delta psi. However, OLC and ouabain block monensin-induced hyperpolarization. The inhibitory effects of OLC, like ouabain, are dose dependent, with half-maximal inhibition occurring at an amount of OLC equivalent to that found in 1.6 g of brain (wet weight) per ml and at 0.85 microM ouabain. In addition, the maximal actions of ouabain and OLC are not additive. These results show that the endogenous OLC specifically affects the delta psi of intact cells by a mechanism analogous to that of ouabain--i.e., inhibition of the Na+,K+-ATPase.

Full text

PDF
1453

Selected References

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

  1. Bricker N. S., Schmidt R. W., Favre H., Fine L., Bourgoignie J. J. On the biology of sodium excretion: The search for a natriuretic hormone. Yale J Biol Med. 1975 Sep;48(4):293–303. [PMC free article] [PubMed] [Google Scholar]
  2. Cantley L. C., Jr, Cantley L. G., Josephson L. A characterization of vanadate interactions with the (Na,K)-ATPase. Mechanistic and regulatory implications. J Biol Chem. 1978 Oct 25;253(20):7361–7368. [PubMed] [Google Scholar]
  3. De Wardener H. E. Natriuretic hormone. Clin Sci Mol Med. 1977 Jul;53(1):1–8. doi: 10.1042/cs0530001. [DOI] [PubMed] [Google Scholar]
  4. Fishman M. C. Endogenous digitalis-like activity in mammalian brain. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4661–4663. doi: 10.1073/pnas.76.9.4661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Flier J. S., Maratos-Flier E., Pallotta J. A., McIsaac D. Endogenous digitalis-like activity in the plasma of the toad Bufo marinus. Nature. 1979 May 24;279(5711):341–343. doi: 10.1038/279341a0. [DOI] [PubMed] [Google Scholar]
  6. Flier J., Edwards M. W., Daly J. W., Myers C. W. Widespread occurrence in frogs and toads of skin compounds interacting with the ouabain site of Na+, K+-ATPase. Science. 1980 May 2;208(4443):503–505. doi: 10.1126/science.6245447. [DOI] [PubMed] [Google Scholar]
  7. Glynn I. M., Karlish S. J. The sodium pump. Annu Rev Physiol. 1975;37:13–55. doi: 10.1146/annurev.ph.37.030175.000305. [DOI] [PubMed] [Google Scholar]
  8. Gorman A. L., Marmor M. F. Steady-state contribution of the sodium pump to the resting potential of a molluscan neurone. J Physiol. 1974 Oct;242(1):35–48. doi: 10.1113/jphysiol.1974.sp010692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gruber K. A., Whitaker J. M., Buckalew V. M., Jr Endogenous digitalis-like substance in plasma of volume-expanded dogs. Nature. 1980 Oct 23;287(5784):743–745. doi: 10.1038/287743a0. [DOI] [PubMed] [Google Scholar]
  10. Haddy F. J., Overbeck H. W. The role of humoral agents in volume expanded hypertension. Life Sci. 1976 Oct 1;19(7):935–947. doi: 10.1016/0024-3205(76)90284-8. [DOI] [PubMed] [Google Scholar]
  11. Haupert G. T., Jr, Sancho J. M. Sodium transport inhibitor from bovine hypothalamus. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4658–4660. doi: 10.1073/pnas.76.9.4658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kuno M., Miyahara J. T., Weakly J. N. Post-tetanic hyperpolarization produced by an electrogenic pump in dorsal spinocerebellar tract neurones of the cat. J Physiol. 1970 Nov;210(4):839–855. doi: 10.1113/jphysiol.1970.sp009245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Lichtshtein D., Dunlop K., Kaback H. R., Blume A. J. Mechanism of monensin-induced hyperpolarization of neuroblastoma-glioma hybrid NG108-15. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2580–2584. doi: 10.1073/pnas.76.6.2580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lichtshtein D., Kaback H. R., Blume A. J. Use of a lipophilic cation for determination of membrane potential in neuroblastoma-glioma hybrid cell suspensions. Proc Natl Acad Sci U S A. 1979 Feb;76(2):650–654. doi: 10.1073/pnas.76.2.650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lichtstein D., Samuelov S. Endogenous 'ouabain like' activity in rat brain. Biochem Biophys Res Commun. 1980 Oct 31;96(4):1518–1523. doi: 10.1016/0006-291x(80)91346-7. [DOI] [PubMed] [Google Scholar]
  17. Lindenmayer G. E. Mechanism of action of digitalis glycosides at the subcellular level. Pharmacol Ther B. 1976;2(4):843–861. doi: 10.1016/0306-039x(76)90081-7. [DOI] [PubMed] [Google Scholar]
  18. Lux H. D. Ionic conditions and membrane behavior. Adv Neurol. 1980;27:63–83. [PubMed] [Google Scholar]
  19. Poston L., Sewell R. B., Wilkinson S. P., Richardson P. J., Williams R., Clarkson E. M., MacGregor G. A., de Wardener H. E. Evidence for a circulating sodium transport inhibitor in essential hypertension. Br Med J (Clin Res Ed) 1981 Mar 14;282(6267):847–849. doi: 10.1136/bmj.282.6267.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smith J. B., Rozengurt E. Serum stimulates the Na+,K+ pump in quiescent fibroblasts by increasing Na+ entry. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5560–5564. doi: 10.1073/pnas.75.11.5560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wallick E. T., Lane L. K., Schwartz A. Biochemical mechanism of the sodium pump. Annu Rev Physiol. 1979;41:397–411. doi: 10.1146/annurev.ph.41.030179.002145. [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