Skip to main content
Log in

Mechanistic principles of ion transport in the Na,K-ATPase

  • Published:
Russian Journal of Electrochemistry Aims and scope Submit manuscript

Abstract

The Na,K-ATPase is a member of the P-type ATPase family and a primary active ion transporter for Na+ and K+ ions in the cytoplasmic membrane of virtually all animal cells. Considerable progress in understanding the ion-pump mechanism of the Na,K-ATPase was gained by combining biophysical and biochemical studies of more than 30 years with structural information at atomic resolution available since recent years. Biophysical studies have revealed detailed properties of the ion movements that led to a gated-channel model which is strongly supported by structural findings obtained for the sodium pump. The basic question of how the free Gibbs energy released by ATP hydrolysis is transferred to the protein and transformed into uphill transport of the ions is still without reply.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Skou, J.C., Biochim. Biophys. Acta, 1957, vol. 23, p. 394.

    Article  CAS  Google Scholar 

  2. Skou, J.C., Biosci. Rep., 1998, vol. 18, p. 155.

    Article  CAS  Google Scholar 

  3. Palmgren, M.G. and Nissen, P., Annu. Rev. Biophys., 2011, vol. 40, p. 243.

    Article  CAS  Google Scholar 

  4. Geering, K., Curr. Opin. Nephrol. Hypertens., 2008, vol. 17, p. 526.

    Article  CAS  Google Scholar 

  5. Garty, H. and Karlish, S.J., Annu. Rev. Physiol., 2006, vol. 68, p. 431.

    Article  CAS  Google Scholar 

  6. Geering, K., Am. J. Physiol Renal Physiol, 2006, vol. 290, pp. F241–F250.

    Article  CAS  Google Scholar 

  7. Dostanic-Larson, I., van Huysse, J.W., Lorenz, J.N., and Lingrel, J.B., Proc. Natl. Acad. Sci. USA, 2005, vol. 102, p. 15845.

    Article  CAS  Google Scholar 

  8. Schoner, W. and Scheiner-Bobis, G., Am. J. Cardiovasc. Drugs, 2007, vol. 7, p. 173.

    Article  CAS  Google Scholar 

  9. Albers, R.W., Ann. Rev. Biochem., 1967, vol. 36, p. 727.

    Article  CAS  Google Scholar 

  10. Post, R.L., Hegyvary, C., and Kume, S., J. Biol. Chem., 1972, vol. 247, p. 6530.

    CAS  Google Scholar 

  11. Apell, H.-J., Rev. Physiol. Biochem. Pharmacol., 2003, vol. 150, p. 1.

    CAS  Google Scholar 

  12. Damnjanovic, B., Weber, A., Potschies, M., et al., Biochemistry, 2013, vol. 52, p. 5563.

    Article  CAS  Google Scholar 

  13. Sweadner, K.J. and Donnet, C., Biochem. J., 2001, vol. 356, p. 685.

    Article  CAS  Google Scholar 

  14. Läuger, P., Electrogenic Ion Pumps, Sunderland, MA, 1991.

    Google Scholar 

  15. Läuger, P., Biochim. Biophys. Acta, 1979, vol. 552, p. 143.

    Article  Google Scholar 

  16. Läuger, P. and Apell, H.-J., Eur. Biophys. J., 1986, vol. 13, p. 309.

    Article  Google Scholar 

  17. Hill, T.L., Free Energy Transduction and Biochemical Cycle Kinetics, New York, 1989.

    Book  Google Scholar 

  18. Heyse, S., Wuddel, I., Apell, H.-J., and Stürmer, W., J. Gen. Physiol., 1994, vol. 104, p. 197.

    Article  CAS  Google Scholar 

  19. Borlinghaus, R., Apell, H.-J., and Läuger, P., J. Membr. Biol., 1987, vol. 97, p. 161.

    Article  CAS  Google Scholar 

  20. Fendler, K., Grell, E., Haubs, M., and Bamberg, E., EMBO J., 1985, vol. 4, p. 3079.

    CAS  Google Scholar 

  21. Sokolov, V.S., Ayuan, A.G., and Apell, H.-J., Eur. Biophys. J., 2001, vol. 30, p. 515.

    Article  CAS  Google Scholar 

  22. Sokolov, V.S., Apell, H.-J., Corrie, J.E., and Trentham, D.R., Biophys. J., 1998, vol. 74, p. 2285.

    Article  CAS  Google Scholar 

  23. Apell, H.-J. and Sokolov, V.S., Pumps, Channels and Transporters, Methods of Functional Analysis, Hoboken, NJ, 2015, p. 23.

    Book  Google Scholar 

  24. Apell, H.-J., Borlinghaus, R., and Läuger, P., J. Membr. Biol., 1987, vol. 97, p. 179.

    Article  CAS  Google Scholar 

  25. Borlinghaus, R. and Apell, H.-J., Biochim. Biophys. Acta, 1988, vol. 939, p. 197.

    Article  CAS  Google Scholar 

  26. Jørgensen, P.L., Meth. Enzymol., 1974, vol. 32, p. 277.

    Article  Google Scholar 

  27. Kaplan, J.H., Forbush, B., and Hoffman, J.F., Biochem., 1978, vol. 17, p. 1929.

    Article  CAS  Google Scholar 

  28. Domaszewicz, W. and Apell, H.-J., FEBS Lett., 1999, vol. 458, p. 241.

    Article  CAS  Google Scholar 

  29. Pintschovius, J. and Fendler, K., Biophys. J., 1999, vol. 76, p. 814.

    Article  CAS  Google Scholar 

  30. Bartolommei, G., Devaux, N., Tadini-Buoninsegni, F., et al., Biophys. J., 2008, vol. 95, p. 1813.

    Article  CAS  Google Scholar 

  31. Wuddel, I. and Apell, H.-J., Biophys. J., 1995, vol. 69, p. 909.

    Article  CAS  Google Scholar 

  32. Sokolov, V.S., Scherbakov, A.A., Lenz, A.A., et al., Biochemistry (Moscow) Suppl. Ser. A: Membr. Cell Biol., 2008, vol. 2, p. 161.

    Article  Google Scholar 

  33. Karlish, S.J.D. and Yates, D.W., Biochim. Biophys. Acta, 1978, vol. 527, p. 115.

    Article  CAS  Google Scholar 

  34. Apell, H.-J. and Bersch, B., Biochim. Biophys. Acta, 1987, vol. 903, p. 480.

    Article  CAS  Google Scholar 

  35. Clarke, R.J., Apell, H.-J., and Läuger, P., Biochim. Biophys. Acta, 1989, vol. 981, p. 326.

    Article  CAS  Google Scholar 

  36. Cornelius, F., Biochim. Biophys. Acta, 1991, vol. 1071, p. 19.

    Article  CAS  Google Scholar 

  37. Apell, H.-J. and Damnjanovic, B., P-Type ATPases, Methods and Protocols, New York, 2016, p. 127.

    Book  Google Scholar 

  38. Stürmer, W., Bühler, R., Apell, H.-J., and Läuger, P., J. Membr. Biol., 1991, vol. 121, p. 163.

    Article  Google Scholar 

  39. Bühler, R., Stürmer, W., Apell, H.-J., and Läuger, P., J. Membr. Biol., 1991, vol. 121, p. 141.

    Article  Google Scholar 

  40. Pedersen, M., Roudna, M., Beutner, S., et al., J. Membr. Biol., 2002, vol. 185, p. 221.

    Article  CAS  Google Scholar 

  41. Apell, H.-J. and Diller, A., FEBS Lett., 2002, vol. 532, p. 198.

    Article  CAS  Google Scholar 

  42. Fibich, A., Janko, K., and Apell, H.J., Biophys. J., 2007, vol. 93, p. 3092.

    Article  CAS  Google Scholar 

  43. Diller, A., Vagin, O., Sachs, G., and Apell, H.-J., Biophys. J., 2005, vol. 88, p. 3348.

    Article  CAS  Google Scholar 

  44. Goldshlegger, R., Karlish, S.J., Rephaeli, A., and Stein, W.D., J. Physiol (Lond.), 1987, vol. 387, p. 331.

    Article  CAS  Google Scholar 

  45. Schneeberger, A. and Apell, H.-J., J. Membr. Biol., 1999, vol. 168, p. 221.

    Article  CAS  Google Scholar 

  46. Schneeberger, A. and Apell, H.-J., J. Membr. Biol., 2001, vol. 179, p. 263.

    Article  CAS  Google Scholar 

  47. Inesi, G., J. Biol. Chem., 1987, vol. 262, p. 16338.

    CAS  Google Scholar 

  48. Holmgren, M., Wagg, J., Bezanilla, F., et al., Nature, 2000, vol. 403, p. 898.

    Article  CAS  Google Scholar 

  49. de Weer, P., Gadsby, D.C., and Rakowski, R.F., The Na+,K+-pump, Part A: Molecular Aspects, NewYork, 1988, p. 421.

    Google Scholar 

  50. Hilgemann, D.W., Science, 1994, vol. 263, p. 1429.

    Article  CAS  Google Scholar 

  51. Nakao, M. and Gadsby, D.C., J. Gen. Physiol., 1989, vol. 94, p. 539.

    Article  CAS  Google Scholar 

  52. Sagar, A. and Rakowski, R.F., J. Gen. Physiol., 1994, vol. 103, p. 869.

    Article  CAS  Google Scholar 

  53. Friedrich, T. and Nagel, G., Biophys. J., 1997, vol. 73, p. 186.

    Article  CAS  Google Scholar 

  54. Gradinaru, R.V. and Apell, H.J., Biochemistry, 2015, vol. 54, p. 2508.

    Article  CAS  Google Scholar 

  55. Gadsby, D.C., Bezanilla, F., Rakowski, R.F., et al., Nat. Commun., 2012, vol. 3, p. 669.

    Article  Google Scholar 

  56. Forbush, B., III, Prog. Clin. Biol. Res. A, 1988, vol. 268, p. 229.

    CAS  Google Scholar 

  57. Bühler, R. and Apell, H.-J., J. Membr. Biol., 1995, vol. 145, p. 165.

    Article  Google Scholar 

  58. Goldshlegger, R., Karlish, S.J., Rephaeli, A., and Stein, W.D., J. Physiol., 1987, vol. 387, p. 331.

    Article  CAS  Google Scholar 

  59. Bahinski, A., Nakao, M., and Gadsby, D.C., Proc. Natl. Acad. Sci. USA, 1988, vol. 85, p. 3412.

    Article  CAS  Google Scholar 

  60. Tosteson, M.T., Bignami, G.S., Scriven, D.R.L., et al., Biochim. Biophys. Acta, 1994, vol. 1191, p. 371.

    Article  CAS  Google Scholar 

  61. Wang, X. and Horisberger, J.-D., FEBS Lett., 1997, vol. 409, p. 391.

    Article  CAS  Google Scholar 

  62. Artigas, P. and Gadsby, D.C., Proc. Natl. Acad. Sci. USA, 2003, vol. 100, p. 501.

    Article  CAS  Google Scholar 

  63. Artigas, P. and Gadsby, D.C., J. Gen. Physiol, 2004, vol. 123, p. 357.

    Article  CAS  Google Scholar 

  64. Harmel, N. and Apell, H.J., J. Gen. Physiol., 2006, vol. 128, p. 103.

    Article  CAS  Google Scholar 

  65. Reyes, N. and Gadsby, D.C., Nature, 2006, vol. 443, p. 470.

    Article  CAS  Google Scholar 

  66. Takeuchi, A., Reyes, N., Artigas, P., and Gadsby, D.C., Nature, 2008, vol. 456, p. 413.

    Article  CAS  Google Scholar 

  67. Toyoshima, C., Nakasako, M., Nomura, H., and Ogawa, H., Nature, 2000, vol. 405, p. 647.

    Article  CAS  Google Scholar 

  68. Møller, J.V., Olesen, C., Winther, A.M., and Nissen, P., Q. Rev. Biophys., 2010, vol. 43, p. 501.

    Article  Google Scholar 

  69. Morth, J.P., Pedersen, B.P., Toustrup-Jensen, M.S., et al., Nature, 2007, vol. 450, p. 1043.

    Article  CAS  Google Scholar 

  70. Shinoda, T., Ogawa, H., Cornelius, F., and Toyoshima, C., Nature, 2009, vol. 459, p. 446.

    Article  CAS  Google Scholar 

  71. Ogawa, H., Shinoda, T., Cornelius, F., and Toyoshima, C., Proc. Natl. Acad. Sci. USA, 2009, vol. 106, p. 13742.

    Article  CAS  Google Scholar 

  72. Laursen, M., Yatime, L., Nissen, P., and Fedosova, N.U., Proc. Natl. Acad. Sci. USA, 2013, vol. 110, p. 10958.

    Article  CAS  Google Scholar 

  73. Laursen, M., Gregersen, J.L., Yatime, L., et al., Proc. Natl. Acad. Sci. USA, 2015, vol. 112, p. 1755.

    Article  CAS  Google Scholar 

  74. Nyblom, M., Poulsen, H., Gourdon, P., et al., Science, 2013, vol. 342, p. 123.

    Article  CAS  Google Scholar 

  75. Kanai, R., Ogawa, H., Vilsen, B., et al., Nature, 2013, vol. 502, p. 201.

    Article  CAS  Google Scholar 

  76. Olesen, C., Picard, M., Winther, A.M., et al., Nature, 2007, vol. 450, p. 1036.

    Article  CAS  Google Scholar 

  77. Toyoshima, C., Norimatsu, Y., Iwasawa, S., et al., Proc. Natl. Acad. Sci. USA, 2007, vol. 104, p. 19831.

    Article  CAS  Google Scholar 

  78. Toyoshima, C. and Nomura, H., Nature, 2002, vol. 418, p. 605.

    Article  CAS  Google Scholar 

  79. Läuger, P., Biochim. Biophys. Acta, 1984, vol. 779, p. 307.

    Article  Google Scholar 

  80. Butscher, C., Roudna, M., and Apell, H.-J., J. Membr. Biol., 1999, vol. 168, p. 169.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hans-Jürgen Apell.

Additional information

Published in Russian in Elektrokhimiya, 2017, Vol. 53, No. 3, pp. 270–281.

The article is published in the original.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Apell, HJ. Mechanistic principles of ion transport in the Na,K-ATPase. Russ J Electrochem 53, 237–247 (2017). https://doi.org/10.1134/S1023193517030028

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1023193517030028

Keywords

Navigation