Journal of Bioenergetics and Biomembranes

, Volume 28, Issue 3, pp 255–267 | Cite as

High-conductance calcium-activated potassium channels; Structure, pharmacology, and function

  • Gregory J. Kaczorowski
  • Hans -Günther Knaus
  • Reid J. Leonard
  • Owen B. McManus
  • Maria L. Garcia
Article

Abstract

High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K+ channels. They are unique in their dual requirement for depolarization and Ca2+ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, α and Β. The α subunit is a member of theslo Ca2+-activated K+ channel gene family and forms the ion conduction pore. The Β subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against α and Β subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets.

Key words

maxi-K channels charybdotoxin iberiotoxin smooth muscle ion channel purification slo channels Β-subunit K channel agonists K channel blockers ion channel pharmacology 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Addy, M. E. (1989).Int. J. Crude Drug Res. 27, 81–91.Google Scholar
  2. Addy, M. E., and Burka, J. F. (1988).Can. J. Physio. Pharmacol. 66, 820–825.Google Scholar
  3. Addy, M. E., and Burka, J. F. (1989).Phytother. Res. 3, 85–90.Google Scholar
  4. Adelman, J. P., Shen, K.-Z., Kavanaugh, M. P., Warren, R. A., Wu, Y.-N., Lagrutta, A., Bond, C. T., and North, R. A. (1992).Neuron. 9, 209–216.PubMedGoogle Scholar
  5. Ampofo, O. (1977).World Health. 26, 28–33.Google Scholar
  6. Anderson, C. S., MacKinnon, R., Smith, C., and Miller, C. (1988).J. Gen. Physiol. 91, 317–333.PubMedGoogle Scholar
  7. Atkinson, N. S., Robertson, G. A., and Ganetzky, B. (1991)Science 253, 551–553.PubMedGoogle Scholar
  8. Bontems, F., Gilquin, B., Roumestand, C., Menez, A., and Toma, F. (1992).Biochemistry 31, 7756–7764.PubMedGoogle Scholar
  9. Bontems, F., Roumestand, C., Boyot, P., Gilquin, B., Doljansky, Y., Menez, A., and Toma, F. (1991).Eur. J. Biochem. 196, 19–28.PubMedGoogle Scholar
  10. Butler, A., Tsunoda, S., McCobb, D. P., Wei, A., and Salkoff, L. (1993).Science 261, 221–224.PubMedGoogle Scholar
  11. Candia, S., Garcia, M. L., and Latorre, R. (1992).Biophys. J. 63, 583–590.PubMedGoogle Scholar
  12. Cecchi, X., Wolff, D., Alvarez, O., and Latorre, R. (1987).Biophys. J. 52, 707–716.PubMedGoogle Scholar
  13. Cole, R. J., and Cox, R. H. (1981). InHandbook of Toxic Fungal Metabolites, Academic Press, New York, pp. 355–509.Google Scholar
  14. Dworetzky, S. I., Trojnacki, J. T., and Gribkoff, V. K. (1994).Mol Brain Res. 27, 189–193.PubMedGoogle Scholar
  15. Edwards, G., Niederste-Hollenberg, A., Schneider, J., Noack, T., and Weston, A. H. (1994).Br. J. Pharmacol. 113, 1530–1547.Google Scholar
  16. Galvez, A., Gimenez-Gallego, G., Reuben, J. P., Roy-Contancin, L., Feigenbaum, P., Kaczorowski, G. J., and Garcia, M. L. (1990).J. Biol. Chem. 265, 11083–11090.PubMedGoogle Scholar
  17. Garcia-Calvo, M., Vazquez, J., Smith, M., Kaczorowski, G. J., and Garcia, M. L. (1991).Biochemistry.30, 11157–11164.PubMedGoogle Scholar
  18. Garcia-Calvo, M., Knaus, H.-G., McManus, O. B., Giangiacomo, K. M., Kaczorowski, G. J., and Garcia, M. L. (1994).J. Biol. Chem. 269, 676–682.PubMedGoogle Scholar
  19. Giangiacomo, K. M., Garcia, M. L., and McManus, O. B. (1992).Biochemistry.31, 6719–6727.PubMedGoogle Scholar
  20. Giangiacomo, K. M., Sugg, E. E., Garcia-Calvo, M., Leonard, R. J., McManus, O. B., Kaczorowski, G. J. and Garcia, M. L. (1993).Biochemistry 32, 2363–2370.PubMedGoogle Scholar
  21. Giangiacomo, K. M., Garcia-Calvo, M., Knaus, H.-G., Mullmann, T. J., Garcia, M. L., and McManus, O. (1995).Biochemistry 34, 15849–15862.PubMedGoogle Scholar
  22. Gimenez-Gallego, G., Navia, M. A., Reuben, J. P., Katz, G. M., Kaczorowski, G. J., and Garcia, M. L. (1988).Proc. Natl. Acad. Sci. USA 85, 3329–3333.PubMedGoogle Scholar
  23. Huang, J.-C., Garcia, M. L., Reuben, J. P., and Kaczorowski, G. J. (1993).Eur. J. Pharmacol. 235, 37–43.PubMedGoogle Scholar
  24. Johnson, B. A., and Sugg, E. E. (1992).Biochemistry 31, 8151–8159.PubMedGoogle Scholar
  25. Jones, T. R., Charette, L., Garcia, M. L., and Kaczorowski, G. J. (1990).J. Pharmacol. Exp. Ther. 255, 697–705.PubMedGoogle Scholar
  26. Jones, T. R., Charette, M. L., Garcia, M. L., and Kaczorowski, G. J. (1993).J. Appl. Physiol. 74, 1879–1884.PubMedGoogle Scholar
  27. King, V. F., Garcia, M. L., Himmel, D., Reuben, J. P., Lam, Y. T., Pan, J., Han, G., and Kaczorowski, G. J. (1988).J. Biol. Chem. 263, 2238–2244.PubMedGoogle Scholar
  28. Knaus, H.-G., Eberhart, A., Kaczorowski, G. J., and Garcia, M. L. (1994a).J. Biol. Chem. 269, 23336–23341.PubMedGoogle Scholar
  29. Knaus, H.-G., Folander, K., Garcia-Calvo, M., Garcia, M. L., Kaczorowski, G. J., Smith, M., and Swanson, R. (1994b).J. Biol. Chem. 269, 17274–17278.PubMedGoogle Scholar
  30. Knaus, H.-G., Garcia-Calvo, M., Kaczorowski, G. J., and Garcia, M. L. (1994c).J. Biol. Chem. 269, 3921–3924.PubMedGoogle Scholar
  31. Knaus, H.-G., McManus, O. B., Lee, S. H., Schmalhofer, W. A., Garcia-Calvo, M., Helms, L. M. H., Sanchez, M., Giangiacomo, K., Reuben, J. P., Smith-III, A. B., Kaczorowski, G. J., and Garcia, M. L. (1994d).Biochemistry 33, 5819–5828.PubMedGoogle Scholar
  32. Knaus, H.-G., Eberhart, A., Koch, R. O. A., Munujos, P., Schmalhofer, W. A., Warmke, J. W., Kaczorowski, G. J., and Garcia, M. L. (1995).J. Biol. Chem. 270, 22434–22439.PubMedGoogle Scholar
  33. Knaus, H.-G., Schwarzer, C., Koch, R. O. A., Eberhart, A., Kaczorowski, G. J., Glossmann, H., Wunder, F., Pongs, O., Garcia, M. L., and Sperk, G. (1996).J. Neurosci. 16, 955–963.PubMedGoogle Scholar
  34. Kume, H., Tokuno, H., and Tomita, T. (1989).Nature 341, 152–154.PubMedGoogle Scholar
  35. Kume, H., Graziano, M. P., and Kotlikoff, M. I. (1992).Proc. Natl. Acad. Sci. USA 89, 11051–11055.PubMedGoogle Scholar
  36. Lambert, P., Kuroda, H., Chino, N., Watanabe, T. X., Kimura, T., and Sakakibara, S. (1990).Biochem. Biophys. Res. Commun. 170, 684–690.PubMedGoogle Scholar
  37. Latorre, R., Oberhauser, A., Labarca, P., and Alvarez, O. (1989).Annu. Rev. Physiol. 51, 385–399.PubMedGoogle Scholar
  38. Laurent, F., Michel, A., Bonnet, P. A., Chapat, J. P., and Boucard, M. (1993).Br. J. Pharmacol. 108, 622–626.PubMedGoogle Scholar
  39. Leonard, R. J., Garcia, M. L., Slaughter, R. S., and Reuben, J. P. (1992).Proc. Natl. Acad. Sci. USA 89, 10094–10098.PubMedGoogle Scholar
  40. Lucchesi, K., Ravindran, A., Young, H., and Moczydlowski, E. (1989).J. Membr. Biol. 109, 269–281.PubMedGoogle Scholar
  41. MacKinnon, R., and Miller, C. (1988).J. Gen. Physiol. 91, 335–349.PubMedGoogle Scholar
  42. MacKinnon, R., and Miller, C. (1989).Biochemistry.28, 8087–8092.PubMedGoogle Scholar
  43. McManus, O. B. (1991).J. Bioenerg. Biomembr. 23, 537–560.PubMedGoogle Scholar
  44. McManus, O. B., Giangiacomo, K. L., Harris, G. H., Addy, M. E., Reuben, J. P., Kaczorowski, G. J. and Garcia, M. L. (1993a).Biophys. J. 64, 3a.Google Scholar
  45. McManus, O. B., Harris, G. H., Giangiacomo, K. M., Feigenbaum, P., Reuben, J. P., Addy, M. E., Burka, J. F., Kaczorowski, G. J., and Garcia, M. L. (1993b).Biochemistry 32, 6128–6133.PubMedGoogle Scholar
  46. McManus, O. B., Helms, L. M. H., Pallanck, L., Ganetzky, B., Swanson, R., and Leonard, R. J. (1995).Neuron 14, 1–20.PubMedGoogle Scholar
  47. Miller, C. (1988).Neuron 1, 1003–1006.PubMedGoogle Scholar
  48. Miller, C., Moczydlowski, E., Latorre, R., and Phillips, M. (1985).Nature 313, 316–318.PubMedGoogle Scholar
  49. Miura, M., Belvesi, M. G., Stretton, C. D., Yacoub, M. H., and Barnes, P. J. (1992).Am. Rev. Respir. Dis. 146, 132–136.PubMedGoogle Scholar
  50. Moss, G. W. J., Marshall, J., Morabito, M., Moczydlowski, E. G., and Howe, J. (1995).Biophys. J. 68, 29a.Google Scholar
  51. Munujos, P., Knaus, H.-G., Kaczorowski, G. J., and Garcia, M. L. (1995).Biochemistry 34, 10771–10776.PubMedGoogle Scholar
  52. Neyton, J., and Miller, C. (1988).J. Gen. Physiol. 92, 549–567.PubMedGoogle Scholar
  53. Norris, P. J., Smith, C. T., DeBelleroche, J., Bradford, H. F., Mantle, P. G., Thomas, A. J., and Penny, R. H. C. (1980).J. Neurochem. 34, 33–42.PubMedGoogle Scholar
  54. Novick, J., Leonard, R. J., King, V. F., Schmalhofer, W., Kaczorowski, G. J., and Garcia, M. L. (1991).Biophys. J. 59, 78a.Google Scholar
  55. Olesen, S.-P., Munch, E., Moldt, P., and Drejer, J. (1994).Eur. J. Pharmacol. 251, 53–59.PubMedGoogle Scholar
  56. Pallanck, L., and Ganetzky, B. (1994).Hum. Mol. Genet. 8, 1239–1243.Google Scholar
  57. Park, C.-S., and Miller, C. (1992a).Neuron 9, 307–313.PubMedGoogle Scholar
  58. Park, C.-S., and Miller, C. (1992b).Biochemistry 31, 7749–7755.PubMedGoogle Scholar
  59. Park, C. S., Hausdorff, S. F., and Miller, C. (1991).Proc. Natl. Acad. Sci. USA 88, 2046–2050.PubMedGoogle Scholar
  60. Quast, U. (1993).Trends Pharmacol. Sci. 14, 332–337.PubMedGoogle Scholar
  61. Reinhart, P. H., Tseng-Crank, J., Krause, J. D., Mertz, R., Godinot, N., DiChiara, T. J., and Foster, C. D. (1995).Biophys. J. 68, 270a.Google Scholar
  62. Robitalle, R., Garcia, M. L., Kaczorowski, G. J., and Charlton, M. P. (1993).Neuron. 11, 645–655.PubMedGoogle Scholar
  63. Sands, S. B., Lewis, R. S., and Cahalan, M. D. (1989).J. Gen Physiol. 93, 1061–1074.PubMedGoogle Scholar
  64. Sargent, C. A., Grover, G. J., Antonaccio, M. J., and McCullough, J. R. (1993).J. Pharmacol. Exp. Ther. 266, 1422–1429.PubMedGoogle Scholar
  65. Schweitz, H., Bidard, J.-N., Maes, P., and Lazdunski, M. (1989).Biochemistry 28, 9708–9714.PubMedGoogle Scholar
  66. Selala, M. I., Laekeman, G. M., Loenders, B., Musuka, A., Herman, A. G., and Schepens, P. (1991).J. Nat. Prod. 54, 207–212.PubMedGoogle Scholar
  67. Singh, S. B., Goetz, M. A., Zink, D. L., Dombrowski, A. W., Polishook, J. D., Garcia, M. L., Schmalhofer, W., McManus, O. B., and Kaczorowski, G. J. (1994).J. Chem. Soc. Perkin Trans. 1, 3349–3352.Google Scholar
  68. Stampe, P., Kolmakova-Partensky, L., and Miller, C. (1992).Biophys. J. 62, 8–9.PubMedGoogle Scholar
  69. Stampe, P., Kolmakova-Partensky, L., and Miller, C. (1994).Biochemistry 33, 443–450.PubMedGoogle Scholar
  70. Stretton, D., Motohiko, M., Belvesi, M. G., and Barnes, P. J. (992).Proc. Natl. Acad. Sci. USA 89, 1325–1329.Google Scholar
  71. Strong, P. N., Weir, S. W., Beech, D. J., Heistand, P., and Kocher, H. P. (1989).Br. J. Pharamacol. 98, 817–826.Google Scholar
  72. Suarez-Kurtz, G., Garcia, M. L., and Kaczorowski, G. J. (1991).J. Pharmacol. Exp. Ther. 259, 439–443.PubMedGoogle Scholar
  73. Sugg, E. E., Garcia, M. L., Reuben, J. P., Patchett, A. A., and Kaczorowski, G. J. (1990).J. Biol. Chem. 265, 18745–18748.PubMedGoogle Scholar
  74. Tseng-Crank, J., Foster, C. D., Krause, J. D., Mertz, R., Godinot, N., DiChiara, T. J., and Reinhart, P. H. (1994).Neuron 13, 1315–1330.PubMedGoogle Scholar
  75. Vazquez, J., Feigenbaum, P., Katz, G., King, V. F., Reuben, J. P., Roy-Contancin, L., Slaughter, R. S., Kaczorowski, G. J., and Garcia, M. L. (1989).J. Biol. Chem. 264, 20902–20909.PubMedGoogle Scholar
  76. Vazquez, J., Feigenbaum, P., King, V. F., Kaczorowski, G. J., and Garcia, M. L. (1990).J. Biol. Chem. 256, 15564–15571.Google Scholar
  77. Vergara, C., and Latorre, R. (1983).J. Gen. Physiol. 82, 543–568.PubMedGoogle Scholar
  78. Villaroel, A., Alvarez, O., Oberhauser, A., and Latorre, R. (1988)Pflügers Arch. 413, 118–126.Google Scholar
  79. Wallner, M., Meera, P., Ottolia, M., Kaczorowski, G., Latorre, R., Garcia, M., Stefani, E., and Toro, L. (1995).Receptors and Channels 3, 185–199.PubMedGoogle Scholar
  80. Ward, J. P. T., Taylor, S. G., and Collier, M. L. (1992).Br. J. Pharmacol. 107, 49P.Google Scholar
  81. Williams, D. L., Katz, G. M., Roy-Contancin, L., and Reuben, J. P. (1988).Proc. Natl. Acad. Sci. USA 85, 9360–9364.PubMedGoogle Scholar
  82. Winquist, R. J., Heany, L. A., Wallace, A. A., Baskin, E. P., Stein, R. B., Garcia, M. L., and Kaczorowski, G. (1989).J. Pharmacol. Exp. Ther. 248, 149–156.PubMedGoogle Scholar
  83. Wolff, D., Cecchi, X., Spalvins, A., and Canessa, M. (1988).J. Membr. Biol. 106, 243–252.PubMedGoogle Scholar
  84. Yao, Y., Peter, A. B., Baur, R., and Sigel, E. (1989).Mol. Pharmacol. 35, 319–323.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Gregory J. Kaczorowski
    • 1
  • Hans -Günther Knaus
    • 2
  • Reid J. Leonard
    • 1
  • Owen B. McManus
    • 1
  • Maria L. Garcia
    • 1
  1. 1.Merck Research LaboratoriesRahway
  2. 2.Institute for Biochemical PharmacologyUniversity of InnsbruckInnsbruckAustria

Personalised recommendations