Skip to main content
SpringerLink
Log in

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

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Addy, M. E. (1989).Int. J. Crude Drug Res. 27, 81–91.

    Google Scholar 

  • Addy, M. E., and Burka, J. F. (1988).Can. J. Physio. Pharmacol. 66, 820–825.

    Google Scholar 

  • Addy, M. E., and Burka, J. F. (1989).Phytother. Res. 3, 85–90.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Ampofo, O. (1977).World Health. 26, 28–33.

    Google Scholar 

  • Anderson, C. S., MacKinnon, R., Smith, C., and Miller, C. (1988).J. Gen. Physiol. 91, 317–333.

    PubMed  Google Scholar 

  • Atkinson, N. S., Robertson, G. A., and Ganetzky, B. (1991)Science 253, 551–553.

    PubMed  Google Scholar 

  • Bontems, F., Gilquin, B., Roumestand, C., Menez, A., and Toma, F. (1992).Biochemistry 31, 7756–7764.

    PubMed  Google Scholar 

  • Bontems, F., Roumestand, C., Boyot, P., Gilquin, B., Doljansky, Y., Menez, A., and Toma, F. (1991).Eur. J. Biochem. 196, 19–28.

    PubMed  Google Scholar 

  • Butler, A., Tsunoda, S., McCobb, D. P., Wei, A., and Salkoff, L. (1993).Science 261, 221–224.

    PubMed  Google Scholar 

  • Candia, S., Garcia, M. L., and Latorre, R. (1992).Biophys. J. 63, 583–590.

    PubMed  Google Scholar 

  • Cecchi, X., Wolff, D., Alvarez, O., and Latorre, R. (1987).Biophys. J. 52, 707–716.

    PubMed  Google Scholar 

  • Cole, R. J., and Cox, R. H. (1981). InHandbook of Toxic Fungal Metabolites, Academic Press, New York, pp. 355–509.

    Google Scholar 

  • Dworetzky, S. I., Trojnacki, J. T., and Gribkoff, V. K. (1994).Mol Brain Res. 27, 189–193.

    PubMed  Google Scholar 

  • Edwards, G., Niederste-Hollenberg, A., Schneider, J., Noack, T., and Weston, A. H. (1994).Br. J. Pharmacol. 113, 1530–1547.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Garcia-Calvo, M., Vazquez, J., Smith, M., Kaczorowski, G. J., and Garcia, M. L. (1991).Biochemistry.30, 11157–11164.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Giangiacomo, K. M., Garcia, M. L., and McManus, O. B. (1992).Biochemistry.31, 6719–6727.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Giangiacomo, K. M., Garcia-Calvo, M., Knaus, H.-G., Mullmann, T. J., Garcia, M. L., and McManus, O. (1995).Biochemistry 34, 15849–15862.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Huang, J.-C., Garcia, M. L., Reuben, J. P., and Kaczorowski, G. J. (1993).Eur. J. Pharmacol. 235, 37–43.

    PubMed  Google Scholar 

  • Johnson, B. A., and Sugg, E. E. (1992).Biochemistry 31, 8151–8159.

    PubMed  Google Scholar 

  • Jones, T. R., Charette, L., Garcia, M. L., and Kaczorowski, G. J. (1990).J. Pharmacol. Exp. Ther. 255, 697–705.

    PubMed  Google Scholar 

  • Jones, T. R., Charette, M. L., Garcia, M. L., and Kaczorowski, G. J. (1993).J. Appl. Physiol. 74, 1879–1884.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Knaus, H.-G., Eberhart, A., Kaczorowski, G. J., and Garcia, M. L. (1994a).J. Biol. Chem. 269, 23336–23341.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Knaus, H.-G., Garcia-Calvo, M., Kaczorowski, G. J., and Garcia, M. L. (1994c).J. Biol. Chem. 269, 3921–3924.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Kume, H., Tokuno, H., and Tomita, T. (1989).Nature 341, 152–154.

    PubMed  Google Scholar 

  • Kume, H., Graziano, M. P., and Kotlikoff, M. I. (1992).Proc. Natl. Acad. Sci. USA 89, 11051–11055.

    PubMed  Google Scholar 

  • Lambert, P., Kuroda, H., Chino, N., Watanabe, T. X., Kimura, T., and Sakakibara, S. (1990).Biochem. Biophys. Res. Commun. 170, 684–690.

    PubMed  Google Scholar 

  • Latorre, R., Oberhauser, A., Labarca, P., and Alvarez, O. (1989).Annu. Rev. Physiol. 51, 385–399.

    PubMed  Google Scholar 

  • Laurent, F., Michel, A., Bonnet, P. A., Chapat, J. P., and Boucard, M. (1993).Br. J. Pharmacol. 108, 622–626.

    PubMed  Google Scholar 

  • Leonard, R. J., Garcia, M. L., Slaughter, R. S., and Reuben, J. P. (1992).Proc. Natl. Acad. Sci. USA 89, 10094–10098.

    PubMed  Google Scholar 

  • Lucchesi, K., Ravindran, A., Young, H., and Moczydlowski, E. (1989).J. Membr. Biol. 109, 269–281.

    PubMed  Google Scholar 

  • MacKinnon, R., and Miller, C. (1988).J. Gen. Physiol. 91, 335–349.

    PubMed  Google Scholar 

  • MacKinnon, R., and Miller, C. (1989).Biochemistry.28, 8087–8092.

    PubMed  Google Scholar 

  • McManus, O. B. (1991).J. Bioenerg. Biomembr. 23, 537–560.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • McManus, O. B., Helms, L. M. H., Pallanck, L., Ganetzky, B., Swanson, R., and Leonard, R. J. (1995).Neuron 14, 1–20.

    PubMed  Google Scholar 

  • Miller, C. (1988).Neuron 1, 1003–1006.

    PubMed  Google Scholar 

  • Miller, C., Moczydlowski, E., Latorre, R., and Phillips, M. (1985).Nature 313, 316–318.

    PubMed  Google Scholar 

  • Miura, M., Belvesi, M. G., Stretton, C. D., Yacoub, M. H., and Barnes, P. J. (1992).Am. Rev. Respir. Dis. 146, 132–136.

    PubMed  Google Scholar 

  • Moss, G. W. J., Marshall, J., Morabito, M., Moczydlowski, E. G., and Howe, J. (1995).Biophys. J. 68, 29a.

    Google Scholar 

  • Munujos, P., Knaus, H.-G., Kaczorowski, G. J., and Garcia, M. L. (1995).Biochemistry 34, 10771–10776.

    PubMed  Google Scholar 

  • Neyton, J., and Miller, C. (1988).J. Gen. Physiol. 92, 549–567.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Novick, J., Leonard, R. J., King, V. F., Schmalhofer, W., Kaczorowski, G. J., and Garcia, M. L. (1991).Biophys. J. 59, 78a.

    Google Scholar 

  • Olesen, S.-P., Munch, E., Moldt, P., and Drejer, J. (1994).Eur. J. Pharmacol. 251, 53–59.

    PubMed  Google Scholar 

  • Pallanck, L., and Ganetzky, B. (1994).Hum. Mol. Genet. 8, 1239–1243.

    Google Scholar 

  • Park, C.-S., and Miller, C. (1992a).Neuron 9, 307–313.

    PubMed  Google Scholar 

  • Park, C.-S., and Miller, C. (1992b).Biochemistry 31, 7749–7755.

    PubMed  Google Scholar 

  • Park, C. S., Hausdorff, S. F., and Miller, C. (1991).Proc. Natl. Acad. Sci. USA 88, 2046–2050.

    PubMed  Google Scholar 

  • Quast, U. (1993).Trends Pharmacol. Sci. 14, 332–337.

    PubMed  Google Scholar 

  • 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 

  • Robitalle, R., Garcia, M. L., Kaczorowski, G. J., and Charlton, M. P. (1993).Neuron. 11, 645–655.

    PubMed  Google Scholar 

  • Sands, S. B., Lewis, R. S., and Cahalan, M. D. (1989).J. Gen Physiol. 93, 1061–1074.

    PubMed  Google Scholar 

  • Sargent, C. A., Grover, G. J., Antonaccio, M. J., and McCullough, J. R. (1993).J. Pharmacol. Exp. Ther. 266, 1422–1429.

    PubMed  Google Scholar 

  • Schweitz, H., Bidard, J.-N., Maes, P., and Lazdunski, M. (1989).Biochemistry 28, 9708–9714.

    PubMed  Google Scholar 

  • Selala, M. I., Laekeman, G. M., Loenders, B., Musuka, A., Herman, A. G., and Schepens, P. (1991).J. Nat. Prod. 54, 207–212.

    PubMed  Google Scholar 

  • 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 

  • Stampe, P., Kolmakova-Partensky, L., and Miller, C. (1992).Biophys. J. 62, 8–9.

    PubMed  Google Scholar 

  • Stampe, P., Kolmakova-Partensky, L., and Miller, C. (1994).Biochemistry 33, 443–450.

    PubMed  Google Scholar 

  • Stretton, D., Motohiko, M., Belvesi, M. G., and Barnes, P. J. (992).Proc. Natl. Acad. Sci. USA 89, 1325–1329.

    Google Scholar 

  • Strong, P. N., Weir, S. W., Beech, D. J., Heistand, P., and Kocher, H. P. (1989).Br. J. Pharamacol. 98, 817–826.

    Google Scholar 

  • Suarez-Kurtz, G., Garcia, M. L., and Kaczorowski, G. J. (1991).J. Pharmacol. Exp. Ther. 259, 439–443.

    PubMed  Google Scholar 

  • Sugg, E. E., Garcia, M. L., Reuben, J. P., Patchett, A. A., and Kaczorowski, G. J. (1990).J. Biol. Chem. 265, 18745–18748.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Vazquez, J., Feigenbaum, P., King, V. F., Kaczorowski, G. J., and Garcia, M. L. (1990).J. Biol. Chem. 256, 15564–15571.

    Google Scholar 

  • Vergara, C., and Latorre, R. (1983).J. Gen. Physiol. 82, 543–568.

    PubMed  Google Scholar 

  • Villaroel, A., Alvarez, O., Oberhauser, A., and Latorre, R. (1988)Pflügers Arch. 413, 118–126.

    Google Scholar 

  • Wallner, M., Meera, P., Ottolia, M., Kaczorowski, G., Latorre, R., Garcia, M., Stefani, E., and Toro, L. (1995).Receptors and Channels 3, 185–199.

    PubMed  Google Scholar 

  • Ward, J. P. T., Taylor, S. G., and Collier, M. L. (1992).Br. J. Pharmacol. 107, 49P.

    Google Scholar 

  • Williams, D. L., Katz, G. M., Roy-Contancin, L., and Reuben, J. P. (1988).Proc. Natl. Acad. Sci. USA 85, 9360–9364.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Wolff, D., Cecchi, X., Spalvins, A., and Canessa, M. (1988).J. Membr. Biol. 106, 243–252.

    PubMed  Google Scholar 

  • Yao, Y., Peter, A. B., Baur, R., and Sigel, E. (1989).Mol. Pharmacol. 35, 319–323.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Merck Research Laboratories, P.O. Box 2000, 07065, Rahway, New Jersey

    Gregory J. Kaczorowski, Reid J. Leonard, Owen B. McManus & Maria L. Garcia

  2. Institute for Biochemical Pharmacology, University of Innsbruck, Peter-Mayr Strasse 1, A-6020, Innsbruck, Austria

    Hans -Günther Knaus

Authors
  1. Gregory J. Kaczorowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hans -Günther Knaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reid J. Leonard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Owen B. McManus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria L. Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaczorowski, G.J., Knaus, H.G., Leonard, R.J. et al. High-conductance calcium-activated potassium channels; Structure, pharmacology, and function. J Bioenerg Biomembr 28, 255–267 (1996). https://doi.org/10.1007/BF02110699

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02110699

Key words

Search

Navigation