1932

Abstract

This article gives a history of the evidence () that animal cell membranes contain pumps that expel sodium ions in exchange for potassium ions; () that the pump derives energy from the hydrolysis of ATP; () that it is thermodynamically reversible—artificially steep transmembrane ion gradients make it run backward synthesizing ATP from ADP and orthophosphate; () that its mechanism is a ping-pong one, in which phosphorylation of the pump by ATP is associated with an efflux of three sodium ions, and hydrolysis of the phosphoenzyme is associated with an influx of two potassium ions; () that each half of the working cycle involves both the transfer of a phosphate group and a conformational change—the phosphate transfer being associated with the occlusion of ions bound at one surface and the conformational change releasing the occluded ions at the opposite surface.

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2002-03-01
2024-04-14
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Literature Cited

  1. Overton E. 1902. Beiträge zur allgemeinen Muskel- und Nerven-Physiologie.. II. Über die Unentbehrlichkeit von Natrium- (oder Lithium-) Ionen für den Contractionsact des Muskels Pflügers Arch. 92:346–86 [Google Scholar]
  2. Bernstein J. 1902. Untersuchengen zur Thermodynamik der bioelektrische Ströme.. Pflügers Arch. 92:521–62 [Google Scholar]
  3. Ostwald W. 1890. Elektrische Eigenschaften halbdurchlässiger Scheidenwände.. Z. Phys. Chem. 6:71–96 [Google Scholar]
  4. Bernstein J. 1912. Elektrobiologie.101 Braunschweig: Vieweg
  5. Bayliss WM. 1915. Principles of General Physiology. London: Longmans Green [Google Scholar]
  6. Fenn WO. 1936. Electrolytes in muscle.. Physiol. Rev. 16:450–87 [Google Scholar]
  7. Huxley AF. 1999. Overton on the indispensability of sodium ions.. Brain Res. Bull. 50:307–8 [Google Scholar]
  8. Fenn WO, Cobb DM. 1936. Electrolyte changes in muscle during activity.. Am. J. Physiol. 115:345–56 [Google Scholar]
  9. Heppel LA. 1940. The diffusion of radioactive sodium into the muscles of potassium-deprived rats.. Am. J. Physiol. 128:449–54 [Google Scholar]
  10. Steinbach HB. 1940. Sodium and potassium in frog muscle.. J. Biol. Chem. 133:695–701 [Google Scholar]
  11. Steinbach HB. 1940. Electrolyte balance of animal cells.. Cold Spring Harbor Symp. Quant. Biol. 8:242–54 [Google Scholar]
  12. Dean RB. 1941. Theories of electrolyte equilibrium in muscle.. Biol. Symp. 3:331–48 [Google Scholar]
  13. Maizels M, Patterson JH. 1940. Survival of stored blood after transfusion.. Lancet 2:417–20 [Google Scholar]
  14. Danowski TS. 1941. The transfer of potassium across the human blood cell membrane.. J. Biol. Chem. 139:693–705 [Google Scholar]
  15. Harris JE. 1941. The influence of the metabolism of human erythrocytes on their potassium content.. J. Biol. Chem. 141:579–95 [Google Scholar]
  16. Conway EJ. 1946. Ionic permeability of skeletal muscle fibres.. Nature 157:715–17 [Google Scholar]
  17. Ussing HH. 1947 . Interpretation of the exchange of radio-sodium in isolated muscle.. Nature 160:262–63 [Google Scholar]
  18. Keynes RD, Swan RC. 1959. The effect of external sodium concentration on the sodium fluxes in frog skeletal muscle.. J. Physiol. 147:591–625 [Google Scholar]
  19. Harris EJ, Maizels M. 1951. The permeability of human red cells to sodium.. J. Physiol. 113:506–24 [Google Scholar]
  20. Keynes RD. 1954. The ionic fluxes in frog muscle.. Proc. R. Soc. London Ser. B 142:359–82 [Google Scholar]
  21. Hodgkin AL, Keynes RD. 1955. Active transport of cations in giant axons from Sepia and Loligo.. J. Physiol. 128:28–60 [Google Scholar]
  22. Glynn IM. 1956. Sodium and potassium movements in human red cells.. J. Physiol. 134:278–310 [Google Scholar]
  23. Post RL, Jolly PC. 1957. The linkage of sodium, potassium and ammonium active transport across the human erythrocyte membrane.. Biochim. Biophys. Acta 25:118–28 [Google Scholar]
  24. Schatzmann HJ. 1953. Herzglycoside als Hemmstoffe für den aktiven Kalium und Natrium Transport durch die Erythrocytenmembran.. Helv. Physiol. Acta 11:346–54 [Google Scholar]
  25. Glynn IM. 1957. The action of cardiac glycosides on sodium and potassium movements in human red cells.. J. Physiol. 136:148–73 [Google Scholar]
  26. Maizels M. 1954. Active cation transport in erythrocytes.. Symp. Soc. Exp. Biol. 8:202–27 [Google Scholar]
  27. Straub FB. 1953. Über die Akkumulation der Kaliumionen durch menschliche Blutkörperchen.. Acta Physiol. Acad. Sci. Hung. 4:235–40 [Google Scholar]
  28. Gárdos G. 1954. Akkumulation der Kaliumionen durch menschliche Blutkörperchen.. Acta Physiol. Acad. Sci. Hung. 6:191–99 [Google Scholar]
  29. Dunham ET. 1957. Linkage of active cation transport to ATP utilization.. Physiologist 1:23 [Google Scholar]
  30. Caldwell PC, Keynes RD. 1957. The utilization of phosphate bond energy for sodium extrusion.. J. Physiol. 137:12–13P [Google Scholar]
  31. Glynn IM. 1957. The ionic permeability of the red cell membrane.. Prog. Biophys. 8:241–307 [Google Scholar]
  32. Skou JC. 1957. The influence of some cations on an adenosinetriphosphatase from peripheral nerves.. Biochim. Biophys. Acta 23:394–401 [Google Scholar]
  33. Skou JC. 1989. The identification of the sodium-pump as the membrane-bound Na+/K+-ATPase: a commentary by J.C. Skou.. Biochim. Biophys. Acta 1000:435–38 [Google Scholar]
  34. Skou JC. 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 42:6–23 [Google Scholar]
  35. Post RL, Merritt CR, Kinsolving CR, Albright CD. 1960. Membrane adenosine triphosphatase as a participant in the active transport of sodium and potassium in the human erythrocyte.. J. Biol. Chem. 235:1796–802 [Google Scholar]
  36. Dunham ET, Glynn IM. 1961. Adenosinetriphosphatase activity and the active movements of alkali metal ions.. J. Physiol. 156:274–93 [Google Scholar]
  37. Glynn IM. 1961. Activation of adenosinetriphosphatase activity in a cell membrane by external potassium and internal sodium.. J. Physiol. 160:18–19P [Google Scholar]
  38. Skou JC. 1962. Preparation from mammalian brain and kidney of the enzyme system involved in active transport of Na+ and K+.. Biochim. Biophys. Acta 58:314–25 [Google Scholar]
  39. Bonting SL, Caravaggio LL. 1963. Studies on Na:K activated ATPase.. V. Correlation of enzyme activity with cation flux in six tissues Arch. Biochem. Biophys. 101:37–46 [Google Scholar]
  40. Garrahan PJ, Glynn IM. 1967. The incorporation of inorganic phosphate into adenosine triphosphate by reversal of the sodium pump.. J. Physiol. 192:237–56 [Google Scholar]
  41. Lew VL, Glynn IM, Ellory JC. 1970. Net synthesis of ATP by reversal of the sodium pump.. Nature 225:865–66 [Google Scholar]
  42. Jorgensen PL, Hansen O, Glynn IM, Cavieres JD. 1973. Antibodies to pig kidney (Na+ + K+)-ATPase inhibit the Na+ pump in human red cells provided they have access to the inner surface of the cell membrane.. Biochim. Biophys. Acta 291:795–800 [Google Scholar]
  43. Sweadner KJ, Goldin SM. 1975. Reconstitution of active ion transport by the sodium and potassium ion-stimulated adenosine triphosphatase from canine brain.. J. Biol. Chem. 250:4022–24 [Google Scholar]
  44. Hilden S, Hokin LE. 1975. Active potassium transport coupled to active sodium transport in vesicles reconstituted from purified sodium and potassium ion-activated adenosine triphosphatase from the rectal gland of Squalus acanthias.. J. Biol. Chem. 250:6296–303 [Google Scholar]
  45. Jørgensen PL. 1982. Mechanism of the Na+,K+ pump.. Protein structure and conformations of the pure (Na++K+)-ATPase Biochim. Biophys. Acta 694:27–68 [Google Scholar]
  46. Taniguchi K, Kaya S. 2000. Na/K-ATPase and related ATPases.. Proc. 9th Int. Conf. Na/K-ATPase and Related ATPases. Sapporo, Japan 1999. Amsterdam: Elsevier 771 pp. [Google Scholar]
  47. Lingrel JB, Kuntzweiler T. 1994. Na+,K+-ATPase.. J. Biol. Chem. 269:19659–62 [Google Scholar]
  48. Toyoshima C, Nakasako M, Nomura H, Ogawa H. 2000. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution.. Nature 405:647–55 [Google Scholar]
  49. Glynn IM. 1985. The Na+,K+-transporting adenosine triphosphatase. In The Enzymes of Biological Membranes, ed. AN Martonosi 335–114 New York/London: Plenum 676 pp. 2nd. ed
  50. Skou JC, Esmann M. 1992. The Na,K-ATPase.. J. Bioenerg. Biomembr. 24:249–61 [Google Scholar]
  51. Robinson JD. 1997. Moving Questions: A History of Membrane Transport and Bioenergetics. New York: Oxford 373 pp. [Google Scholar]
  52. Albers RW, Fahn S, Koval GJ. 1963. The role of sodium ions in the activation of Electrophorus electric organ adenosine triphosphatase.. Proc. Natl. Acad. Sci. USA 50:474–81 [Google Scholar]
  53. Charnock JS, Post RL. 1963. Evidence of the mechanism of ouabain inhibition of cation activated adenosine triphosphatase.. Nature 199:910–11 [Google Scholar]
  54. Post RL, Sen AK, Rosenthal AS. 1965. A phosphorylated intermediate in adenosine triphosphate-dependent sodium and potassium transport across kidney membranes.. J. Biol. Chem. 240:1437–45 [Google Scholar]
  55. Post RL, Kume S. 1973. Evidence for an aspartyl phosphate residue at the active site of sodium and potassium ion transport adenosine triphosphatase.. J. Biol. Chem. 248:6993–7000 [Google Scholar]
  56. Garrahan PJ, Glynn IM. 1967. The behaviour of the sodium pump in red cells in the absence of external potassium.. J. Physiol. 192:159–74 [Google Scholar]
  57. Garrahan PJ, Glynn IM. 1967. Factors affecting the relative magnitudes of the sodium:potassium and sodium:sodium exchanges catalysed by the sodium pump.. J. Physiol. 192:189–216 [Google Scholar]
  58. Keynes RD, Steinhardt RA. 1968. The components of the sodium efflux in frog muscle.. J. Physiol. 198:581–99 [Google Scholar]
  59. Baker PF, Blaustein MP, Keynes RD, Manil J, Shaw TI, Steinhardt RA. 1969. The ouabain-sensitive fluxes of sodium and potassium in squid giant axons.. J. Physiol. 200:459–96 [Google Scholar]
  60. Glynn IM, Hoffman JF. 1971. Nucleotide requirements for sodium-sodium exchange catalysed by the sodium pump in human red cells.. J. Physiol. 218:239–56 [Google Scholar]
  61. Cavieres JD, Glynn IM. 1979. Sodium-sodium exchange through the sodium pump: the roles of ADP and ATP.. J. Physiol. 297:637–45 [Google Scholar]
  62. Cavieres JD. 1980. Extracellular sodium stimulates ATP-ADP exchange by the sodium pump.. J. Physiol. 308:57P [Google Scholar]
  63. Kaplan JH, Hollis RJ. 1980. External Na dependence of ouabain-sensitive ATP-ADP exchange initiated by photolysis of intracellular caged-ATP in human red cell ghosts.. Nature 288:587–89 [Google Scholar]
  64. Fahn S, Koval GJ, Albers RW. 1966. Sodium-potassium-activated adenosine triphosphatase of Electrophorus electric organ.. I. An associated sodium-activated transphosphorylation J. Biol. Chem. 241:1882–89 [Google Scholar]
  65. Garrahan PJ, Glynn IM. 1967. The stoichiometry of the sodium pump.. J. Physiol. 192:217–35 [Google Scholar]
  66. Glynn IM, Lew VL, Lüthi U. 1970. Reversal of the potassium entry mechanism in red cells, with and without reversal of the entire pump cycle.. J. Physiol. 207:371–91 [Google Scholar]
  67. Simons TJB. 1974. Potassium-potassium exchange catalysed by the sodium pump in human red cells.. J. Physiol. 237:123–55 [Google Scholar]
  68. Simons TJB. 1975. The interaction of ATP analogs possessing a blocked γ-phosphate group with the sodium pump in human red cells.. J. Physiol. 244:731–39 [Google Scholar]
  69. Sachs JR. 1981. Mechanistic implications of the potassium-potassium exchange carried out by the sodium-potassium pump.. J. Physiol. 316:263–77 [Google Scholar]
  70. Dahms AS, Boyer PD. 1973. Occurrence and characteristics of 18O exchange reactions catalyzed by sodium- and potassium-dependent adenosine triphosphatases.. J. Biol. Chem. 248:3155–62 [Google Scholar]
  71. Hegyvary C, Post RL. 1971. Binding of adenosine triphosphate to sodium and potassium ion-stimulated adenosine triphosphatase.. J. Biol. Chem. 246:5234–40 [Google Scholar]
  72. Nørby JG, Jensen J. 1971. Binding of ATP to brain microsomal ATPase.. Determination of the ATP-binding capacity and the dissociation constant of the enzyme-ATP complex as a function of K+ concentration Biochim. Biophys. Acta 233:104–16 [Google Scholar]
  73. Jørgensen PL. 1975. Purification and characterization of (Na++K+)-ATPase.. V. Conformational changes in the enzyme. Transitions between the Na-form and the K-form studied with tryptic digestion as a tool Biochim. Biophys. Acta 401:399–415 [Google Scholar]
  74. Jørgensen PL, Petersen J. 1979. Protein conformations of the phosphorylated intermediates of purified Na,K-ATPase studied with tryptic digestion and intrinsic fluorescence as tools. In Na,K-ATPase: Structure and Kinetics, ed. JC Skou, JG Nørby 143–55 London: Academic
  75. Karlish SJD, Yates DW. 1978. Tryptophan fluorescence of (Na+ + K+)-ATPase as a tool for study of the enzyme mechanism.. Biochim. Biophys. Acta 527:115–30 [Google Scholar]
  76. Glynn IM, Karlish SJD. 1990. Occluded cations in active transport.. Annu. Rev. Biochem. 59:171–205 [Google Scholar]
  77. Post RL, Hegyvary C, Kume S. 1972. Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase.. J. Biol. Chem. 247:6530–40 [Google Scholar]
  78. Karlish SJD, Yates DW, Glynn IM. 1978. Conformational transitions between Na+-bound and K+-bound forms of (Na++K+)-ATPase, studied with formycin nucleotides.. Biochim. Biophys. Acta 525:252–64 [Google Scholar]
  79. Beaugé LA, Glynn IM. 1979. Occlusion of K ions in the unphosphorylated sodium pump.. Nature 280:510–12 [Google Scholar]
  80. Glynn IM, Hara Y, Richards DE, Steinberg M. 1987. Comparison of rates of cation release and of conformational change in dog kidney Na,K-ATPase.. J. Physiol. 383:477–85 [Google Scholar]
  81. Glynn IM, Richards DE. 1982. Occlusion of rubidium ions by the sodium-potassium pump: its implications for the mechanism of potassium transport.. J. Physiol. 330:17–43 [Google Scholar]
  82. Blostein R, Chu L. 1977. Sidedness of (sodium, potassium)-adenosine triphosphatase of inside-out red cell membrane vesicles.. Interactions with potassium J. Biol. Chem. 252:3035–43 [Google Scholar]
  83. Jørgensen PL, Skriver E, Hebert H, Maunsbach AB. 1982. Structure of the Na,K pump: crystallisation of pure membrane-bound Na,K-ATPase and identification of functional domains of the α-subunit.. Ann. NY Acad. Sci. 402:207–24 [Google Scholar]
  84. Glynn IM, Hara Y, Richards DE. 1984. The occlusion of sodium ions within the mammalian sodium-potassium pump: its role in sodium transport.. J. Physiol. 351:531–47 [Google Scholar]
  85. Glynn IM, Howland JL, Richards DE. 1985. Evidence for the ordered release of rubidium ions occluded within the Na,K-ATPase of mammalian kidney.. J. Physiol. 368:453–69 [Google Scholar]
  86. Forbush B. 1987. Rapid release of 42K or 86Rb from two distinct transport sites on the Na,K-pump in the presence of Pi or vanadate.. J. Biol. Chem. 262:11116–27 [Google Scholar]
  87. Glynn IM, Richards DE. 1989. Evidence for the ordered release of rubidium ions occluded within individual protomers of dog kidney Na,K-ATPase.. J. Physiol. 408:57–66 [Google Scholar]
  88. Lee JA, Fortes PAG. 1985. Anthroylouabain binding to different phosphoenzyme forms of Na,K-ATPase. In The Sodium Pump, ed. I Glynn, C Ellory 277–82 Cambridge, UK: Company of Biologists
  89. Yoda A, Yoda S. 1987. Two different phosphorylation-dephosphorylation cycles of Na,K-ATPase proteoliposomes accompanying Na+ transport in the absence of K+.. J. Biol. Chem. 262:110–15 [Google Scholar]
  90. Jørgensen PL. 1991. Conformational transitions in the α-subunit and ion occlusion. In The Sodium Pump: Structure, Mechanism and Regulation, Society of General Physiologists Series, ed. JH Kaplan, P De Weer 46(1)189–200 New York: Rockefeller Univ. Press
  91. Taniguchi K, Kaya S, Abe K, Mårdh S. 2001. The oligomeric nature of Na/K-transport ATPase.. J. Biochem. 129:335–42 [Google Scholar]
  92. Donnett C, Arystarkhova E, Sweadner K. 2001. Thermal denaturation of the Na,K-ATPase provides evidence for α-α oligomeric interaction and γ subunit association with the C-terminal domain.. J. Biol Chem. 276:7357–65 [Google Scholar]
  93. Martin DW, Sachs JR. 1992. Cross-linking of the erythrocyte (Na+,K+)-ATPase.. J. Biol. Chem. 267:23922–29 [Google Scholar]
  94. Hayashi Y, Mimura K, Matsui H, Takagi T. 1989. Minimum enzyme unit for Na+/K+-ATPase is the αβ protomer: determination by low-angle laser light scattering photometry coupled with high-performance gel chromatography for substantially simultaneous measurement of ATPase activity and molecular weight.. Biochim. Biophys. Acta 983:217–29 [Google Scholar]
  95. Martin DW, Sachs JR. 1999. Preparation of Na+,K+-ATPase with near maximal specific activity and phosphorylation capacity: evidence that the reaction mechanism involves all of the sites.. Biochemistry 38:7485–97 [Google Scholar]
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