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. 1977 Jan;264(2):449–470. doi: 10.1113/jphysiol.1977.sp011677

Kinetics of the inhibition of the Na-K pump by external sodium.

J R Sachs
PMCID: PMC1307771  PMID: 839462

Abstract

1. When the ouabain-sensitive K influx or the ouabain-sensitive Cs influx is measured as a function of the extracellular concentration of K or Cs in Na-free solutions the resulting saturation curve at first rises more rapidly than a rectangular hyperbola, i.e. the curve is antisigmoid. 2. If the ouabain-sensitive K influx or the ouabain-sensitive Cs influx is measured in Na-free solutions at a fixed low concentration of K or Cs and at varying concentrations of Li, the influx decreases monotonically as the Li concentration rises and there is no evidence of competitive activation. 3. These findings can be accounted for by a model which proposes that there are two binding sites for K or Cs and that both the singly loaded and doubly loaded pump is capable of transport. 4. Extracellular Na changes the shape of both the K and the Cs saturation curve from antisigmoid to sigmoid. Dixon plots (1/ouabain-sensitive influx versus Na concentration at fixed K or Cs concentration) are linear at intermediate concentrations of K or Cs. 5. Na does not change the rate of K influx if the measurements are made at nearly saturating K concentrations using cells with nearly saturating internal Na concentrations. The effect of outside Na cannot therefore be explained by any mechanism which requires that Na alter the Vmax of the pump. 6. Measurement of the ouabain-sensitive Cs influx as a function of the external Cs concentration in solutions with different fixed Na concentrations results in curves which change from antisigmoid in Na-free solutions to sigmoid as the Na concentration rises. Dixon plots are linear at all but the lowest and highest Cs concentrations. 7. The resulting curves are best fit by equations which result from a model which proposes that Na acts both as a dead-end competitive inhibitor and as a heterotropic allosteric effector. Simpler models which propose either that Na acts solely as a dead-end competitive inhibitor or as a heterotropic allosteric effector do not fit as well as the more complicated model. 8. The combined competitive inhibition and allosteric effector model also describes adequately the relation between the ouabain-sensitive K influx and external K concentration measured at different external Na concentrations.

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Selected References

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

  1. Cavieres J. D., Ellory J. C. Allosteric inhibition of the sodium pump by external sodium. Nature. 1975 May 22;255(5506):338–340. doi: 10.1038/255338a0. [DOI] [PubMed] [Google Scholar]
  2. Cavieres J. D., Ellory J. C. Thallium and the sodium pump in human red cells. J Physiol. 1974 Nov;243(1):243–266. doi: 10.1113/jphysiol.1974.sp010752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chipperfield A. R., Whittam R. Evidence that ATP is hydrolysed in a one-step reaction of the sodium pump. Proc R Soc Lond B Biol Sci. 1974 Nov 5;187(1088):269–280. doi: 10.1098/rspb.1974.0074. [DOI] [PubMed] [Google Scholar]
  4. Garay R. P., Garrahan P. J. The interaction of sodium and potassium with the sodium pump in red cells. J Physiol. 1973 Jun;231(2):297–325. doi: 10.1113/jphysiol.1973.sp010234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Garrahan P. J., Glynn I. M. The sensitivity of the sodium pump to external sodium. J Physiol. 1967 Sep;192(1):175–188. doi: 10.1113/jphysiol.1967.sp008295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Garrahan P. J., Glynn I. M. The stoicheiometry of the sodium pump. J Physiol. 1967 Sep;192(1):217–235. doi: 10.1113/jphysiol.1967.sp008297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Garrahan P. J., Rega A. F. Cation loading of red blood cells. J Physiol. 1967 Nov;193(2):459–466. doi: 10.1113/jphysiol.1967.sp008371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hobbs A. S., Dunham P. B. Letter: Evidence for two sodium sites on the external aspect of Na-K pump in human erythrocytes. Nature. 1976 Apr 15;260(5552):651–652. doi: 10.1038/260651a0. [DOI] [PubMed] [Google Scholar]
  9. Hoffman P. G., Tosteson D. C. Active sodium and potassium transport in high potassium and low potassium sheep red cells. J Gen Physiol. 1971 Oct;58(4):438–466. doi: 10.1085/jgp.58.4.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kropp D. L., Sachs J. R. Kinetics of the inhibition of the Na-K pump by tetrapropylammonium chloride. J Physiol. 1977 Jan;264(2):471–487. doi: 10.1113/jphysiol.1977.sp011678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lew V. L., Hardy M. A., Jr, Ellory J. C. The uncoupled extrusion of Na+ through the Na+ pump. Biochim Biophys Acta. 1973 Oct 11;323(2):251–266. doi: 10.1016/0005-2736(73)90149-1. [DOI] [PubMed] [Google Scholar]
  12. Lindenmayer G. E., Schwartz A., Thompson H. K., Jr A kinetic description for sodium and potassium effects on (Na+ plus K+)-adenosine triphosphatase: a model for a two-nonequivalent site potassium activation and an analysis of multiequivalent site models for sodium activation. J Physiol. 1974 Jan;236(1):1–28. doi: 10.1113/jphysiol.1974.sp010419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. POST R. L., JOLLY P. C. The linkage of sodium, potassium, and ammonium active transport across the human erythrocyte membrane. Biochim Biophys Acta. 1957 Jul;25(1):118–128. doi: 10.1016/0006-3002(57)90426-2. [DOI] [PubMed] [Google Scholar]
  14. Post R. L., Albright C. D., Dayani K. Resolution of pump and leak components of sodium and potassium ion transport in human erythrocytes. J Gen Physiol. 1967 May;50(5):1201–1220. doi: 10.1085/jgp.50.5.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Priestland R. N., Whittam R. The influence of external sodium ions on the sodium pump in erythrocytes. Biochem J. 1968 Sep;109(3):369–374. doi: 10.1042/bj1090369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Robinson J. D. Variable affinity of the (Na+ + K+)-dependent adenosine triphosphatase for potassium. Studies using beryllium inactivation. Arch Biochem Biophys. 1973 May;156(1):232–243. doi: 10.1016/0003-9861(73)90361-5. [DOI] [PubMed] [Google Scholar]
  17. SEN A. K., POST R. L. STOICHIOMETRY AND LOCALIZATION OF ADENOSINE TRIPHOSPHATE-DEPENDENT SODIUM AND POTASSIUM TRANSPORT IN THE ERYTHROCYTE. J Biol Chem. 1964 Jan;239:345–352. [PubMed] [Google Scholar]
  18. SKOU J. C. The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta. 1957 Feb;23(2):394–401. doi: 10.1016/0006-3002(57)90343-8. [DOI] [PubMed] [Google Scholar]
  19. Sachs J. R. Competitive effects of some cations on active potassium transport in the human red blood cell. J Clin Invest. 1967 Sep;46(9):1433–1441. doi: 10.1172/JCI105635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sachs J. R., Ellory J. C., Kropp D. L., Dunham P. B., Hoffman J. F. Antibody-induced alterations in the kinetic characteristics of the Na:K pump in goat red blood cells. J Gen Physiol. 1974 Apr;63(4):389–414. doi: 10.1085/jgp.63.4.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sachs J. R. Interaction of external K, Na, and cardioactive steroids with the Na-K pump of the human red blood cell. J Gen Physiol. 1974 Feb;63(2):123–143. doi: 10.1085/jgp.63.2.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sachs J. R. Recoupling the Na-K pump. J Clin Invest. 1972 Dec;51(12):3244–3247. doi: 10.1172/JCI107151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sachs J. R., Welt L. G. The concentration dependence of active potassium transport in the human red blood cell. J Clin Invest. 1967 Jan;46(1):65–76. doi: 10.1172/JCI105512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wu S. C., Sjodin R. A. The interactions of potassium, sodium and strophanthidin during active transport of sodium ions in frog muscle cells. Biochim Biophys Acta. 1972 Dec 1;290(1):327–338. doi: 10.1016/0005-2736(72)90075-2. [DOI] [PubMed] [Google Scholar]

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