Pharmacology of voltage-gated potassium channels

Abstract

Peptide toxins have been important tools for the analysis of the structure and function of potassium channels. They may bind with high specificity to voltage-gated potassium (Kv) channels and thereby alter their activity. This binding may either block the Kv channel pore or may modify Kv channel gating. This article discusses recent advances in our knowledge of Kv channel structure in relation to known toxin binding sites at the extracellular surface of Kv channels. Two principally different toxin receptor sites have been discovered: (i) the outer mouth of the pore; (ii) the S3/S4-linker region at some distance away from the pore.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Hille, B., Ionic Channels of Excitable Membranes, Second Edition (1992) Sunderland, Massachusetts: Sinauer Associates, Inc.

    Google Scholar 

  2. 2.

    Papazian, D.M., Schwarz, T.L., Tempel, B.L., Jan, Y.N. and Jan, J.Y., Science, 237 (1987) 749.

    Google Scholar 

  3. 3.

    Kamb, A., Iverson, L.E. and Tanouye, M.A., Cell, 50 (1987) 405.

    Google Scholar 

  4. 4.

    Pongs, O., Kecskemethy, N., Müller, R., Krah-Jentgens, I., Baumann, A., Kiltz, H.H., Canal, I., Lamazares, S. and Ferrus, A., EMBO J., 7 (1988) 1087.

    Google Scholar 

  5. 5.

    Tempel, B.L., Jan, Y.N. and Jan, L.Y., Nature, 332 (1988) 837.

    Google Scholar 

  6. 6.

    Stühmer, W., Stocker, U., Sakmann, B., Seeburg, P., Baumann, A., Gruppe, A. and Pongs, O., FEBS Lett., 241 (1988) 199.

    Google Scholar 

  7. 7.

    Stühmer, W., Ruppersberg, J.P., Schröter, K.H., Sakmann, B., Stocker, M., Giese, K.P., Perschke, A., Baumann, A. and Pongs, O., EMBO J., 8 (1989) 3235.

    Google Scholar 

  8. 8.

    MacKinnon, R., Nature, 350 (1991) 232.

    Google Scholar 

  9. 9.

    Isacoff, E.Y., Jan, Y.N. and Jan, L.Y., Nature, 345 (1990) 530.

    Google Scholar 

  10. 10.

    Ruppersberg, J.P., Schröter, K.H., Sakmann, B., Stocker, M., Sewing, S. and Pongs, O., Nature, 345 (1990) 535.

    Google Scholar 

  11. 11.

    Christie, M.J., North, R.A., Osborne, P.B., Douglass, J. and Adelman, J.P., Neuron, 4 (1990) 405.

    Google Scholar 

  12. 12.

    Rettig, R., Heinemann, R.H., Wunder, F., Lorra, C., Parcej, D.N., Dolly, J.O. and Pongs, O., Nature, 369 (1994) 289.

    Google Scholar 

  13. 13.

    Rehm, H. and Lazdunski, M., Proc. Natl. Acad. Sci. USA, 85 (1988) 4919.

    Google Scholar 

  14. 14.

    Parcej, D.N. and Dolly, J.O., Biochem. J., 257 (1989) 899.

    Google Scholar 

  15. 15.

    Heinemann, S.H., Rettig, J., Graack, H.R. and Pongs, O., J. Physiol., 493 (1996) 625.

    Google Scholar 

  16. 16.

    Chandy, G. and Gutman, G.A., in North, R.A. (Ed.), Handbook of Receptors and Channels, CRC Press, Boca Raton, FL, 1994, pp. 1–71.

    Google Scholar 

  17. 17.

    Li, M., Jan, Y.N. and Jan, L.Y., Science, 257 (1992) 1225.

    Google Scholar 

  18. 18.

    Shen, V. and Pfaffinger, P., Neuron, 14 (1995) 625.

    Google Scholar 

  19. 19.

    Yu, W., Xu, J. and Li, M., Neuron, 16 (1996) 441.

    Google Scholar 

  20. 20.

    Sewing, S., Roeper, J. and Pongs, O., Neuron, 16 (1996) 455.

    Google Scholar 

  21. 21.

    Papazian, D.M., Timpe, L.C., Jan, Y.N. and Jan, L.Y., Nature, 349 (1991) 305.

    Google Scholar 

  22. 22.

    Seoh, S.-A., Sigg, D., Papazian, D.M. and Bezanilla, F., Neuron, 16 (1996) 1159.

    Google Scholar 

  23. 23.

    Yool, A.J. and Schwarz, T.L., Nature, 349 (1991) 700.

    Google Scholar 

  24. 24.

    Hartmann, H.A., Kirsch, G.E., Drewe, J.A., Joho, R.H. and Brown, A.M., Science, 251 (1991) 942.

    Google Scholar 

  25. 25.

    Durrell, S.R. and Guy, H.R., Neuropharmacology, 35 (1996) 761.

    Google Scholar 

  26. 26.

    Gómez, J.M., Lorra, C., Pardo, L.A., Stühmer, W., Pongs, O., Heinemann, S.H. and Elliott, A.A., Pflügers Archiv., 434 (1997) 661.

    Google Scholar 

  27. 27.

    Lopez, G.A., Jan, Y.N. and Jan, L.Y., Nature, 367 (1994) 179.

    Google Scholar 

  28. 28.

    Heginbotham, L., Lu, Z., Abramson, T. and MacKinnon, R., Biophys. J., 66 (1994) 1061.

    Google Scholar 

  29. 29.

    Hoshi, T., Zagotta, W.N. and Aldrich, R.W., Science, 250 (1990) 533.

    Google Scholar 

  30. 30.

    Choi, K.L., Aldrich, R.W. and Yellen, G., Proc. Natl. Acad. Sci. USA, 88 (1991) 5092.

    Google Scholar 

  31. 31.

    Kim, E., Niethammer, M., Rothschild, A., Jan, Y.N. and Sheng, M., Nature, 378 (1995) 85.

    Google Scholar 

  32. 32.

    Warmke, J.W. and Ganetzky, B., Proc. Natl. Acad. Sci. USA, 91 (1994) 3438.

    Google Scholar 

  33. 33.

    Charlier, C., Singh, N.A., Ryan, S.G., Lewis, T.B., Reus, B.E., Leach, R.J. and Leppert, M., Nature Genet., 18 (1998) 53.

    Google Scholar 

  34. 34.

    Salinas, M., deWeille, J., Guillemare, E., Lazdunski, M. and Hugnot, J.P., J. Biol. Chem., 272 (1997) 8774.

    Google Scholar 

  35. 35.

    Patel, A.J., Lazdunski, M. and Honoré, E., EMBO J., 16 (1997) 6615.

    Google Scholar 

  36. 36.

    Post, M.A., Kirsch, G.E., and Brown, A.M., FEBS Lett., 399 (1996) 177.

    Google Scholar 

  37. 37.

    Hanner, M., Schmalhofer, W.A., Munujos, P., Knaus, H.G., Kaczorowski, G.J. and Garcia, M.L., Proc. Natl. Acad. Sci. USA, 94 (1997) 2853.

    Google Scholar 

  38. 38.

    Bekele-Arcuri, Z., Matos, M.F., Manganas, L., Strassle, B.W., Monaghan, M.M., Rhodes, K.J. and Trimmer, J.S., Neuropharmacology, 35 (1996) 851.

    Google Scholar 

  39. 39.

    Romey, G., Attali, B., Chouabe, C., Abtibols, I., Guillemare, E., Barhanin, J. and Lazdunski, M., J. Biol. Chem., 272 (1997) 16713.

    Google Scholar 

  40. 40.

    Tang, C.Y. and Papazian, D.M., J. Gen. Physiol., 109 (1997) 301.

    Google Scholar 

  41. 41.

    Gross, A. and MacKinnon, R., Neuron 16 (1996) 399.

    Google Scholar 

  42. 42.

    Goldstein, S.A.N., Pheasant, D.J. and Miller, C., Neuron, 12 (1994) 1377.

    Google Scholar 

  43. 43.

    Aiyar, J., Withka, J.M., Rizzi, J.P., Singleton, D.H., Andrews, G.C., Lin, W., Boyd, J., Hanson, D.C., Simon, M., Dethlefs, B., Lee, C.L., Hall, J.E., Gutman, G.A. and Chandy, K.G., Neuron, 15 (1995) 1169.

    Google Scholar 

  44. 44.

    Goldstein, S.A.N. and Miller, C., Biophys. J., 65 (1993) 1613.

    Google Scholar 

  45. 45.

    Hidalgo, P. and MacKinnon, R., Science, 268 (1995) 307.

    Google Scholar 

  46. 46.

    Lipkind, G.M. and Fozzard, H.A., J. Membrane Biol., 158 (1997) 187.

    Google Scholar 

  47. 47.

    Krovetz, H.S., Van Dongen, H.M.A. and Van Dongen, A.M.J., Biophys. J., 72 (1997) 117.

    Google Scholar 

  48. 48.

    Swartz, K.J. and MacKinnon, R., Neuron, 18 (1997) 665.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pongs, O. Pharmacology of voltage-gated potassium channels. Perspectives in Drug Discovery and Design 15, 215–225 (1999). https://doi.org/10.1023/A:1017080529858

Download citation

  • charybdotoxin
  • dendrotoxin
  • Kv channels
  • Shaker