The (Sodium plus Potassium)-Transport ATPase

  • R. W. Albers


The (Na+ + K+) ATPase (EC is the enzymatic expression of the principal active cation-transport system in eucaryotic cells. In a number of tissues—brain, electric organ, kidney, salt glands, etc.—it constitutes the main mechanism for producing physiological work. Thus the mechanism of this enzyme is of great interest both in terms of cell physiology and molecular biology. The questions of most fundamental interest relate to (1) how the free energy of hydrolysis of ATP is channeled into vectorial work, (2) the molecular structure of the ionophoric mechanism, and (3) how the active transport mechanism is regulated to conform to the requirements of the cell.


Active Transport Electric Organ Salt Gland Adenosine Triphosphatase Sodium Pump 


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  1. Albers, R. W., 1967, Biochemical aspects of active transport, Annu. Rev. Biochem. 36:727.PubMedCrossRefGoogle Scholar
  2. Albers, R. W., and Koval, G. J., 1973, Sodium-potassium-activated adenosine triphosphatase of Electrophorus electric organ. VIII. Monovalent cation sites regulating phosphatase activity, J. Biol. Chem. 248:777.PubMedGoogle Scholar
  3. Albers, R. W., Koval, G. J., and Siegel, G. J., 1968, Studies on the interaction of ouabain and other cardioactive steroids with sodium-potassium-activated adenosine triphosphatase, Mol. Pharmacol. 4:324.PubMedGoogle Scholar
  4. Albers, R. W., Koval, G. J., and Swann, A. C., 1974, Analysis of Na +, K +, and nucleotide interactions in terms of a heterotropic relaxation model for (Na++K +)-ATPase, Ann. N.Y. Acad. sci. 242:268.PubMedCrossRefGoogle Scholar
  5. Baker, P. F., 1972, Transport and metabolism of calcium ions in nerve, in: Progress in Biophysics and Molecular Biology (J. Butler and D. Noble, eds.), Vol. 24, pp. 177–223, Pergamon Press, New York.Google Scholar
  6. Baker, P. F., and Stone, A. J., 1966, A kinetic method for investigating hypothetical models of the sodium pump, Biochim. Biophys. Acta 126:321.PubMedCrossRefGoogle Scholar
  7. Bernstein, J., 1902, Untersuchungen zur Thermodynamik der bioelektrischen Ströme, Pfluegers Arch. Gesamte Physiol. Menschen Tiere, 92:521.CrossRefGoogle Scholar
  8. Boardman, L., Huett, M., Lamb, J. F., Newton, J. P., and Polson J. M., 1974, Evidence for the genetic control of the sodium pump density in HeLa cells, J. Physiol. 241:771.PubMedGoogle Scholar
  9. Bogdanski, D. F., and Brodie, B. B., 1969, The effects of inorganic ions on the storage and uptake of 3H-norepinephrine by rat heart slices, J. Pharmacol. Exp. Therap. 165:181.Google Scholar
  10. Bonting, S. L., 1970, Sodium-potassium activated adenosinetriphosphatase and cation transport, in: Membranes and Ion Transport (E. Bittar, ed.), Vol. 1, pp. 286–392, Wiley-Interscience, New York.Google Scholar
  11. Caldwell, P. C., 1969, Energy relationships and the active transport of ions, Current Top. Bioenerg. 3:251–278.Google Scholar
  12. Caldwell, P. C., Hodgkin, A. L., Keynes, R. D., and Shaw, T. I., 1960, The effects of injecting “energy-rich” phosphate compounds on the active transport of ions in the giant axons of Loligo, J. Physiol. 152:561.PubMedGoogle Scholar
  13. Carpenter, D. O., 1970, Membrane potential produced directly by the Na+ pump in Aplysia neurons, Comp. Biochem. Physiol. 35:371.CrossRefGoogle Scholar
  14. Collins, R. C., and Albers, R. W., 1972, The phosphoryl acceptor protein of Na-K-ATPase from various tissue, J. Neurochem. 19:1209PubMedCrossRefGoogle Scholar
  15. Conway, E. J., and Hingerty, D., 1948, Relations between potassium and sodium levels in mammalian muscle and blood plasma, Biochem. J. 42:372.Google Scholar
  16. Dahl, J. L., and Hokin, L. E., 1974, The sodium-potassium adenosinetriphosphatase, Annu. Rev. Biochem. 43:327.PubMedCrossRefGoogle Scholar
  17. De Weer, P., 1970, Effects of intracellular adenosine5′-diphosphate and orthophosphate on the sensitivity of sodium efflux from squid axon to external sodium and potassium, J. Gen. Physiol. 56:583.PubMedCrossRefGoogle Scholar
  18. De Weer, P., 1974, Na +, K+ exchange and Na +, Na+ exchange in the giant axon of the squid, Ann. N.Y. Acad. Sci. 242:434.PubMedCrossRefGoogle Scholar
  19. Dixon, J. F., and Hokin, L. E., 1974, Studies on the characterization of the sodium-potassium transport adenosine triphosphatase, Arch. Biochem. Biophys. 163:749.PubMedCrossRefGoogle Scholar
  20. Edelman, I. S., 1974, Thyroid and sodium transport, in: Drugs and Transport Processes (B. A. Calling-ham, ed.), pp. 101–110, Macmillan, London.Google Scholar
  21. Epstein, F. H., and Silva, P., 1974, Role of sodium, potassium-ATPase in renal function, Ann. N.Y. Acad. Sci. 242:519.PubMedCrossRefGoogle Scholar
  22. Epstein, F. H., Katz, A. I., and Pickford, G. E., 1967, Sodium-and potassium-activated adenosine triphosphatase of gills: Role in adaptation of teleosts to salt water, Science 156:1245.PubMedCrossRefGoogle Scholar
  23. Fahn, S., Koval, G. J., and Albers, R. W., 1966, Sodium-potassium-activated adenosine triphosphatase of Electrophorus electric organ. I. An associated sodium-activated transphosphorylation, J. Biol. Chem. 241:1882.PubMedGoogle Scholar
  24. Garay, R. P., and Garrahan, P. J., 1973, The interaction of sodium and potassium with the solid pump in red cells, J. Physiol. 231:297.PubMedGoogle Scholar
  25. Garrahan, P. J., and Garay, R. P., 1974, A kinetic study of the Na pump in red cells; Its relevance to the mechanism of active transport, Ann. N.Y. Acad. Sci. 242:445.PubMedCrossRefGoogle Scholar
  26. Garrahan, P. J., and Glynn, I. M., 1967a, The sensitivity of the sodium pump to external sodium, J. Physiol. (London) 192:175.Google Scholar
  27. Garrahan, P. J., and Glynn, I. M., 1967b, Factors affecting the relative magnitude of the sodium-potassium and sodium-sodium exchanges catalysed by the sodium pump, J. Physiol. (London) 192:189.Google Scholar
  28. Garrahan, P. J., and Glynn, I. M., 1967c, The stoichiometry of the sodium pump, J. Physiol. (London) 192:217.Google Scholar
  29. Garrahan, P. J., and Glynn, I. M., 1967d, The incorporation of inorganic phosphate into adenosine, triphosphate by reversal of the sodium pump, J. Physiol. (London) 192:237.Google Scholar
  30. Glynn, I. M., and Hoffman, J., 1971, Nucleotide requirements for sodium-sodium exchange catalysed by the sodium pump in human red cells, J. Physiol. (London) 218:239.Google Scholar
  31. Glynn, I. M., and Karlish, S. J. D., 1975, The sodium pump, Anna. Rev. Physiol. 37:13.CrossRefGoogle Scholar
  32. Glynn, I. M., Lew, V. L., and Luthi, LI., 1970, Reversal of the potassium entry mechanism in red cells, with and without reversal of the entire pump cycle, J. Physiol. 207:371.PubMedGoogle Scholar
  33. Goldin, S. M., and Tong, S. W., 1974, Reconstitution of active transport catalysed by the purified sodium and potassium ion-stimulated adenosine triphosphatase from canine renal medulla, J. Biol. Chem. 249:5907.PubMedGoogle Scholar
  34. Goldman, S., 1975, Cold resistance of the brain during hibernation: Evidence of a lipid adaptation, Am. J. Physiol. 228:834.PubMedGoogle Scholar
  35. Grinstein, S., and Erlij, D., 1974, Insulin unmasks latent sodium pump sites in frog muscle, Nature 251:57.PubMedCrossRefGoogle Scholar
  36. Hansen, O., 1972, The relationship between G-strophanthin-binding capacity and ATPase activity in plasma-membrane fragments from ox brain, Biochim. Biophys. Acta. 233:122.Google Scholar
  37. Harris, E. J., and Maizels, M., 1951, The permeability of human erythrocytes to sodium, J. Physiol. 113:506.PubMedGoogle Scholar
  38. Hegyvary, C., and Post, R. L., 1971, Binding of adenosine triphosphate to sodium and potassium ion-stimulated adenosine triphosphatase, J. Biol. Chem. 246:5234.PubMedGoogle Scholar
  39. Heppel, L. A., 1940, The diffusion of radioactive sodium into the muscles of potassium-depleted rats, Am. J. Physiol. 127:385.Google Scholar
  40. Hilden, S., Rhee, H., and Hokin, L. E., 1974, Sodium transport by phospholipid vesicles containing purified sodium and potassium ion-activated adenosine triphosphatase, J. Biol. Chem. 249:7432.PubMedGoogle Scholar
  41. Hokin, L. E., 1974, Purification and properties of the (sodium and potassium)-activated adenosine triphosphatase and reconstitution of sodium transport, Ann. N.Y. Acad. Sci. 242:12.PubMedCrossRefGoogle Scholar
  42. Ismail-Beigi, F., and Edelman, I. S., 1970, Mechanism of thyroid calorigenesis: role of active sodium transport, Proc. Natl. Acad. Sci. U.S.A. 67:1071.CrossRefGoogle Scholar
  43. Jarnefelt, J., 1972, Lipid requirements of functional membrane structures as indicated by the reversible inactivation of (Na++K +)-ATPase, Biochim. Biophys. Acta 266:91.PubMedCrossRefGoogle Scholar
  44. Jean, D. H., Albers, R. W., and Koval, G. J., 1975, Sodium-potassium-activated adenosine triphosphatase of Electrophorus electric organ. X. Immuno-chemical properties of the Lubrol-solubilized enzyme and its constituent polypeptides, J. Biol. Chem. 250:1035.PubMedGoogle Scholar
  45. Jensen, J., and Norby, J. G., 1971, On the specificity of the ATP-binding site of (Na++K+-activated ATPase from brain microsomes, Biochim. Biophys. Acta 233:395.PubMedCrossRefGoogle Scholar
  46. Jørgensen, P. L., 1972, The role of aldosterone in the regulation of (Na++K +)-ATPase in rat kidney, J. Steroid Biochem. 3:181.PubMedCrossRefGoogle Scholar
  47. Jørgensen, P. L., 1974a, Purification of (Na++K+)-ATPase: Active site determinations and purity, Ann. N.Y. Acad. Sci. 242:36.PubMedCrossRefGoogle Scholar
  48. Jørgensen, P. L., 1974b, Purification and characterization of (Na++K+)-ATPase, Biochim. Biophys. Acta 356:36.PubMedCrossRefGoogle Scholar
  49. Kanazawa, T., Saito, M., and Tonomura, Y., 1970, Formation and decomposition of a phos-phorylated intermediate in the reaction of Na+-K +-dependent ATPase, J. Biochem. 67:693.PubMedGoogle Scholar
  50. Karlish, S. J. D., and Glynn, I. M., 1974, An uncoupled efflux of sodium ions from human red cells, probably associated with Na +-dependent ATPase activity, Ann. N.Y. Acad. Sci. 242:261.CrossRefGoogle Scholar
  51. Knox, W. H., and Sen, A. K., 1974, Mechanism of action of aldosterone with particular reference to (Na++K +)-ATPase, Ann. N.Y. Acad. Sci. 242:471.PubMedCrossRefGoogle Scholar
  52. Kyte, J., 1971, Purification of the sodium-and potassium-dependent adenosine triphosphatase from canine renal medulla, J. Biol. Chem. 246:4157.PubMedGoogle Scholar
  53. Leib, W. R., and Stein, W. D., 1974, Simultaneity, occlusion and the sodium pump, Nature 252:730.CrossRefGoogle Scholar
  54. Lindenmayer, G. E., and Schwartz, A., 1973, Nature of the transport adenosine triphosphatase complex, J. Biol. Chem. 248:1291.PubMedGoogle Scholar
  55. Lindenmayer, G. E., Laughter, A. H., and Schwartz, A., 1968, Incorporation of inorganic phosphate-32 into a Na +, K +-ATPase preparation: Stimulation by ouabain, Arch. Biochim. Biophys. 127:187.CrossRefGoogle Scholar
  56. Lindenmayer, G. E., Schwartz, A., and Thompson, H. K., 1974, A kinetic description for (Na++K +)-adenosine triphosphatase, J. Physiol. 236:1.PubMedGoogle Scholar
  57. Luly, P., Barnabei, O., and Tria, E., 1972, Hormonal control in vitro of plasma membrane-bound (Na +-F +)-ATPase of rat liver, Biochim. Biophys. Acta 282:447.PubMedCrossRefGoogle Scholar
  58. MÅrdh, S., and Zetterqvist, O., 1974, Phosphorylation and dephosphorylation reactions of bovine brain Na +, K +-stimulated ATP phosphohydrolase by adenosine [32P] triphosphate by a rapid-mixing technique, Biochim. Biophys. Acta 350:473.PubMedGoogle Scholar
  59. Matty, A. J., and Green, K., 1962, Active sodium transport in response to thyroxine, Life Sci. 1:487.PubMedCrossRefGoogle Scholar
  60. Mullins, L. J., 1972, Active transport of Na+ and K+ across the squid axon membrane, in: Role of Membranes in Secretory Processes (L. Bolis, R. Keynes, and W. Wilbrandt, eds.), pp. 182–202, Elsevier, New York.Google Scholar
  61. Nakao, T., Tashima, K., Nagano, K., and Nakao, M., 1965, Highly specific sodium-potassium-activated adenosine triphosphatase from various tissues of rabbit, Biochem. Biophys. Res. Commun. 19:755.PubMedCrossRefGoogle Scholar
  62. Nakao, M., Nakao, T., Hara, Y., Nagai, F., Yagasaki, S., Koi, M., Nakagawa, A., and Kawai, K., 1974, Purification and properties of (Na++K +)-ATPase from pig brain, Ann. N.Y. Acad. Sci. 242:24.PubMedCrossRefGoogle Scholar
  63. Noguchi, T., and Freed, S., 1971, Dissociation of lipid components and reconstitution at — 75°C of Mg++ dependent, Na+ and K+ stimulated, adenosine triphosphatase in rat brain, Nature 230:148.Google Scholar
  64. Norby, J. G., and Jensen, J., 1971, Binding of ATP to brain microsomal ATPase, Biochim. Biophys. Acta 233:104.PubMedCrossRefGoogle Scholar
  65. Pickford, G. E., Griffith, R. W., Toretti, J., Ernesto, H., and Epstein, F. H., 1970, Branchial reduction and renal stimulation of (Na+, K +)-ATPase by prolactin in hypophysectomized killifish in fresh water, Nature 228:378.PubMedCrossRefGoogle Scholar
  66. Post, R. L., and Sen, A. K., 1967, Sodium and potassium-stimulated ATPase, in: Methods in Enzymology (R. Estabrook and M. Pullman, eds.), Vol. X, pp. 762–768, Academic Press, New York.Google Scholar
  67. Post, R. L., Kume, S., Tobin, T., Orcutt, B., and Sen, A. K., 1969, Flexibility of an active center in sodium-plus-potassium adenosine triphosphatase, J. Gen. Physiol. 54:3065.CrossRefGoogle Scholar
  68. Post, R. L., Hegyvary, G., and Kume, S., 1972, Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase, J. Biol. Chem. 247:6530.PubMedGoogle Scholar
  69. Post, R. L., Toda, G., and Rogers, F. N., 1975a, Phosphorylation by inorganic phosphate of sodium plus potassium ion transport adenosine triphosphatase, J. Biol. Chem. 250:691.PubMedGoogle Scholar
  70. Post, R. L., Toda, G., Kume, S., and Taniguchi, K., 1975b, Synthesis of adenosine triphosphate by way of potassium-sensitive phosphoenzyme of sodium-potassium adenosine triphosphatase, J. Supramol. Structure, in press.Google Scholar
  71. Robinson, J. D., 1973, Variable affinity of the (Na++K+)-dependent adenosine triphosphatase for potassium. Studies using beryllium inactivation, Arch. Biochem. Biophys. 156:232.PubMedCrossRefGoogle Scholar
  72. Robinson, J. D., 1974a, Free Mg++ and proposed isomerizations of (Na++K +)-dependent ATPase, FEBS Lett. 47:352.PubMedCrossRefGoogle Scholar
  73. Robinson, J. D., 1974b, Cation interactions with different functional states of the Na +, K +-ATPase, Ann. N.Y. Acad. Sci. 242:185.PubMedCrossRefGoogle Scholar
  74. Roeloesen, B., and van Deenen, L., 1973, Lipid requirement of membrane-bound ATPase, Eur. J. Biochem. 40:245.CrossRefGoogle Scholar
  75. Sachs, J. R., and Welt, L. G., 1967, The concentration dependence of active K+ transport in the human red blood cell, J. Clin. Invest. 46:65.PubMedCrossRefGoogle Scholar
  76. Schaefer, A., Seregi, A., and Komlos, M., 1974, Ascorbic acid-like effect of the soluble fraction of rat brain on ATPase and its relation to catecholamines and chelating agents, Biochem. Pharmacol. 23:2257.PubMedCrossRefGoogle Scholar
  77. Schatzman, H., 1953, Herzglykoside als Hemmstoffe für den aktiven Kalium und Natrium Transport durch die Erytrhrocytenmembran, Helv. Physiol. Pharmacol. Acta 11:346.Google Scholar
  78. Schmidt, U., and Dubach, U. C., 1974, Sensitivity of Na K adenosine triphosphatase activity in various structures of the rat nephron: Studies with adrenalectomy, Eur. J. Clin. Invest. 1:307.CrossRefGoogle Scholar
  79. Schultz, S. G., Frizzell, R. A., and Nellans, H. N., 1974, Ion transport by mammalian small intestine, Annu. Rev. Physiol. 36:51.PubMedCrossRefGoogle Scholar
  80. Shamoo, A. E., 1974, Isolation of a sodium-dependent ionophore from (Na++K+)-ATPase preparations, Ann. N. Y. Acad. Sci. 242:389.PubMedCrossRefGoogle Scholar
  81. Shaw, T. I., 1954, Sodium and potassium movements in red cells, Ph.D. Thesis, University of Cambridge.Google Scholar
  82. Siegel, G. J., and Albers, R. W., 1967, Sodium-potassium-activated adenosine triphosphatase of Electrophorus electric organ. IV. Modification of responses to Na+ and K+ by arsenite plus 2,3-dimercaptopropanol, J. Biol. Chem. 242:4972.PubMedGoogle Scholar
  83. Siegel, G. J., and Albers, R. W., 1970, Nucleoside triphosphate phosphohydrolases, in: Handbook of Neurochemistry (A. Lajtha, ed.), Vol. 4, pp. 13–44, Plenum Press, New York.Google Scholar
  84. Siegel, G. J., and Goodwin, B., 1972, Sodium-potassium activated adenosine triphosphatase: potassium regulation of enzyme phosphorylation, J. Biol. Chem. 247:3630.PubMedGoogle Scholar
  85. Siegel, G. J., Koval, G. J., and Albers, R. W., 1969, Sodium-potassium-activated adenosine triphosphatase. VI. Characterization of the phosphoprotein formed from orthophosphate in the presence of ouabain, J. Biol. Chem. 244:3264.PubMedGoogle Scholar
  86. Simons, T. J. B., 1974, Potassium: potassium exchange catalysed by the sodium pump in human red cells, J. Physiol, 237:123.PubMedGoogle Scholar
  87. Simpkins, H., and Hokin, L. E., 1973, Studies on the characterization of the sodium-potassium transport adenosine triphosphatase. XIII. On the organization and role of phospholipids in the purified enzyme, Arch. Biochem. Biophys. 159:897.CrossRefGoogle Scholar
  88. Skou, J. C., 1957, The influence of some cations on an adenosine triphosphatase from peripheral nerves, Biochim. Biophys. Acta 23:394.PubMedCrossRefGoogle Scholar
  89. Skou, J. C., 1960, Further investigations on a Mg+++Na+-activated adenosinetriphosphatase, possibly related to the active, linked transport of Na+ and K+ across the nerve membrane, Biochim. Biophys. Acta 42:6.CrossRefGoogle Scholar
  90. Skou, J. C., 1962, Preparation from mammalian brain and kidney of the enzyme system involved in active transport of Na+ and K +, Biochim. Biophys. Acta 58:314.PubMedCrossRefGoogle Scholar
  91. Skou, J. C., 1973, The relationship of the (Na++K +)-activated enzyme system to transport oe sodium and potassium across the cell membrane, Bioenergetics 4:1.CrossRefGoogle Scholar
  92. Sullivan, C. W., and Volcani, B. E., 1974, Synergistically stimulated (Na +, K +)-adenosine triphosphatase from plasma membrane of a marine diatom, Proc. Natl. Acad. Sci. U.S.A. 71:4376.PubMedCrossRefGoogle Scholar
  93. Swann, A. C., and Albers, R. W., 1975a, Sodium+potassium-activated ATPase of mammalian brain: Regulation of phosphatase activity, Biochim. Biophys. Acta 382:437.PubMedCrossRefGoogle Scholar
  94. Swann, A. C., and Albers, R. W., 1975b, (Na +, K +)-Adenosine triphosphatase of mammalian brain: Interactions with Mg++, Biochim. Biophys. Acta, in press.Google Scholar
  95. Taniguchi, K., and Post, R. L., 1975, Synthesis of adenosine triphosphate and exchange between inorganic phosphate and adenosine triphosphate in sodium and potassium ion transport adenosine triphosphatase, J. Biol. Chem. 250:3010.PubMedGoogle Scholar
  96. Thomas, R. C., 1972, Electrogenic sodium pump in nerve and muscle cells, Physiol. Rev. 52:563.PubMedGoogle Scholar
  97. Tobin, T., Akera, T., Baskin, S., and Brody, T., 1973, Calcium ion and sodium-and potassium-dependent adenosine triphosphatase: Its mechanism of inhibition and identification of the E1-P intermediate, Mol. Pharmacol. 9:336.PubMedGoogle Scholar
  98. Tosteson, D. C., 1963, Regulation of cell volume by sodium and potassium transport, in: The Cellular Functions of Membrane Transport (J. F. Hoffman, ed.), pp. 3–22, Prentice-Hall, Englewood Cliffs, New Jersey.Google Scholar
  99. Uesugi, S., Dulak, N. C., Dixon, J. F., Hexum, T. D., Dahl, J. L., Perdue J. F., and Hokin, L. E., 1971, Studies on the characterization of the sodium-potassium transport adenosine triphosphatase. VI. Large scale partial purification and properties of a Lubrol-solubilized brain enzyme, J. Biol. Chem. 246:531.PubMedGoogle Scholar
  100. Vaughan, G., and Cook, J., 1972, Regeneration of cation-transport capacity in HeLa cell membranes after specific blockade by ouabain, Proc. Natl. Acad. Sci. U.S.A. 69:2627.PubMedCrossRefGoogle Scholar
  101. Whittam, R., 1964, The interdependence of metabolism and active transport, in: The Cellular Functions of Membrane Transport (J. F. Hoffman, ed.), pp. 139–154, Prentice-Hall, Englewood Cliffs, New Jersey.Google Scholar
  102. Yoshimura, K., 1973, Activation of Na-K activated ATPase in rat brain by catecholamine, J. Biochem. 71:389.Google Scholar

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© Plenum Press, New York 1976

Authors and Affiliations

  • R. W. Albers
    • 1
  1. 1.Laboratory of Neurochemistry, NINDSNational Institutes of HealthBethesdaUSA

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