Characterization of the Sulfonylurea-Sensitive ATP-Modulated Potassium Channel

  • Henri Bernardi
  • Michel Lazdunski


ATP-sensitive K+ channels constitute a new class of K+ channels that link membrane potential variations to the bioenergetic situation of the cell (Noma, 1983). K+ channels of this class (KATP channels) are regulated by variations of the internal ATP concentration. At high ATP concentrations the channel is closed. When the concentration of ATP becomes lower the channel opens. Therefore, a low ATP concentration will tend to give a hyperpolarization, whereas higher ATP concentrations will tend to lead to the closing of the KATP channel and produce a depolarization (Ashcroft et al., 1984; Rorsman and Trube, 1985).


KATP Channel Mixed Anhydride Photoaffinity Label Ventral Pallidus Sulfonylurea Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aguilar-Bryan, L., Nelson, D. A., Vu, Q. A., Humphrey, M. B, and Boyd III, A. E. 1990. Photoaffinity labeling and partial purification of the 0-cell sulfonylurea receptor using a novel, biologically active glyburide analog. J. Biol. Chem., 265: 8218–8224.PubMedGoogle Scholar
  2. Ashcroft, F. M., Harrison, D. E., and Ashcroft, J. H. 1984. Glucose induces closure of single potassium channels in isolated rat pancreatic ß cells. Nature, 312: 446–447.PubMedCrossRefGoogle Scholar
  3. Ashford, M. L. J., Sturgess, N. L., Trout, N. J., Gardner, N. J., and Hales, C. N. 1988. Adenosine-5’triphosphate-sensitive ion channels in neonatal rat cultured central neurones. Pflügers Arch., 412: 297–304.PubMedCrossRefGoogle Scholar
  4. Amoroso, S., Schmid-Antomarchi, H., Fosset, M., and Lazdunski, M. 1990. Glucose, antidiabetic sulfonylureasGoogle Scholar
  5. and neurotransmitter release. Role of ATP-sensitive K+ channels. Science, 247: 852–854.Google Scholar
  6. Bayley, H., and Knowbes, J. R. 1977. Photoaffinity labelling. Meth. Enzymol., 46: 69–114.PubMedCrossRefGoogle Scholar
  7. Bernardi, H., Fosset, M., and Lazdunski, M. 1988. Characterization, purification and affinity labeling of the brain [3H]glibenclamide binding protein, a putative neuronal ATP-regulated K+ channel. Proc. Natl. Acad. Sei. USA, 86: 2971–2975.Google Scholar
  8. Chamberlain, J. P. 1979. Detection of radioactivity in polyacrylamide gels with the water soluble fluor, sodium salicylate. Anal. Biochem. 98: 132–135.PubMedCrossRefGoogle Scholar
  9. Crooks, M. J., and Brown, K. F. 1974. The binding of sulphonylureas to serum albumin. J. Pharm. Pharmacol., 26: 304–311.PubMedCrossRefGoogle Scholar
  10. De Weille, J. R., Schmid-Antomarchi, H., Fosset, M., and Lazdunski, M. 1988. ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone. Proc. Natl. Acad. Sci. USA, 85: 1312–1316.PubMedCrossRefGoogle Scholar
  11. De Weille, J. R., Schmid-Antomarchi, H., Fosset, M., and Lazdunski, M. 1989a. Regulation of ATP-sensitive K’ channels in insulinoma cells: Activation by somatostatin and kinase C and the role of cAMP. Proc. Natl. Acad. Sci. USA, 86: 2971–2975.PubMedCrossRefGoogle Scholar
  12. De Weille, J. R., Fosset, M., Mourre, C., Schmid-Antomarchi, H., Bernardi, H., and Lazdunski, M. 1989b.Google Scholar
  13. Pharmacology and regulation of ATP-sensitive K+ channels. Pflügers Arch.,414:S80–S87.Google Scholar
  14. Dunne, M. J., and Petersen, O. H. 1986. Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin-secreting cell line. FEBS Lett., 208: 59–62.PubMedCrossRefGoogle Scholar
  15. Edwards, G., and Weston, A. H. 1990. Structure-activity relationship of K+ channel openers. Trends Pharmacol. Sci., 11: 417–422.PubMedCrossRefGoogle Scholar
  16. Fosset, M., De Weille, J. R., Green. R. D., Schmid-Antomarchi, H., and Lazdunski, M. 1988. Antidiabetic sulfonylureas control action potential in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels. J. Biol. Chem., 263: 7933–7936.Google Scholar
  17. Gaines, K. L., Hamilton, S., and Boyd III, A. E. 1988. Characterization of the sulfonylurea receptor on beta cell membranes. J. Biol. Chem., 263: 2589–2592.PubMedGoogle Scholar
  18. Gehlert, D. R., Mais, D. E., Gackenheimer, S. L., Krushinski, J. H., and Robertson, D. W. 1990. Localization of ATP-sensitive K+ channels in the rat brain using a novel radioligand, [‘25l]iodoglibenclamide. Fur. J. Pharmacol., 186: 373–375.Google Scholar
  19. Geisen, K. H., Hitzel, V., Ökomonopoulos, R., Punter, J. Weyer. R. J., and Summ, H. D. 1985. Inhibition of [3H]glibenclamide binding to sulfonylurea receptors by oral antidiabetics. Arzneim. Forsch., 35: 707–712.Google Scholar
  20. Henquin, J. C., and Meissner, H. P. 1982. Opposite effects of tolbutamide and diazoxide on 86Rb+ fluxes and membrane potential in pancreatic 0-cells. Biochem. Pharmacol., 31: 1407–1415.PubMedCrossRefGoogle Scholar
  21. Kaubish, N., Hammer, R., Wollheim, C., Renold, A. E., and Offord, R. E. 1982. Specific receptors for sulfonylureas in brain and in a 0-cell tumor of the rat. Biochem. Pharmacol., 6: 1171–1174.CrossRefGoogle Scholar
  22. Kramer, W., Ökomonopoulos, R., Punter, J., and Summ, H. D. 1988. Direct photoaffinity labeling of the putative sulfonylurea receptor in rat 0-cell tumor membranes by [3H]glibenclamide. FEBS Lett., 229: 355–359.PubMedCrossRefGoogle Scholar
  23. Lamed, R., Levin, Y., and Wilchek, M. 1973. Covalent coupling of nucleotides to agarose for affinity chromatography. Biochim. Biophys. Acta, 304: 231–235.PubMedCrossRefGoogle Scholar
  24. Misler, S., Falke, L. C., Gillis, K., and McDaniel, M. L. 1986. A metabolite-regulated potassium channel in rat pancreatic 0-cells. Proc. Natl. Acad. Sci. USA, 83: 7119–7123.PubMedCrossRefGoogle Scholar
  25. Mourre, C., Hugues, M., and Lazdunski, M. 1986. Quantitative autoradiographic mapping in rat brain of the receptor of apamin, a polypeptide toxin specific for one class of Cat+-dependent K+ channels. Brain Res., 382: 239–249.PubMedCrossRefGoogle Scholar
  26. Mourre, C., Ben Ari, Y., Bernardi, H., Fosset, M., and Lazdunski, M. 1989. Antidiabetic sulfonylureas: Localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices. Brain Res., 486: 159–164.PubMedCrossRefGoogle Scholar
  27. Mourre, C., Smith, M. L., Siesjö, B. K., and Lazdunski, M. 1990a. Brain ischemia alters the density of binding sites for glibenclamide, a specific blocker of ATP-sensitive K+ channels. Brain Res., 526: 147–152.PubMedCrossRefGoogle Scholar
  28. Mourre, C., Widmann, C., and Lazdunski, M. 1990b. Sulfonylurea binding sites associated with ATP-regulated K+ channels in the central nervous system: Autoradiographic analysis of their distribution and ontogenesis, and of their localization in mutant mice cerebellum. Brain Res., 519: 29–43.PubMedCrossRefGoogle Scholar
  29. Noma, A. 1983. ATP-regulated potassium channels in cardiac muscle. Nature, 305: 147–148.PubMedCrossRefGoogle Scholar
  30. Peterson, G. L. 1977. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal. Biochem., 83: 346–356.PubMedCrossRefGoogle Scholar
  31. Quast, U. 1988. Inhibitor of the effects of the K’ channel stimulator cromakalim (BRL 34915) in vascular smooth muscle by glibenclamide and forskolin. Naunyn-Schmiedeberg’s Arch. Pharmacol., 337:suppl. RF2.Google Scholar
  32. Quast, U., and Cook, N. S. 1988. Potent inhibitors of the effect of the K’ channel opener BRL 34915 on vascular smooth muscle. Br. J. Pharmacol., 93: 204 p.Google Scholar
  33. Quast, U., and Cook, N. S. 1989. Moving together, K’ channels openers and ATP-sensitive K’ channels. Trends Pharmacol. Sei., 10: 431–435.CrossRefGoogle Scholar
  34. Robertson, D. W., Schoher, D. A., Krushinski, J. H., Mais, D. E., Thompson, D. C., and Gehlert, D. R. 1990. Expedient synthesis and biochemical properties of an [125I]labeled analogue of glyburide, a radioligand for ATP-inhibited potassium channels. J. Med. Chem., 33: 31234–3126.Google Scholar
  35. Rorsman, P., and Trube, G. 1985. Glucose dependent K’ channels in pancreatic 3-cells are regulated by intracellular ATP. Pflügers Arch., 405: 305–309.PubMedCrossRefGoogle Scholar
  36. Schmid-Antomarchi, H., De Weille, J. R., Fosset, M., and Lazdunski, M. 1987a. The antidiabetic sulfonylurea glibenclamide is a potent blocker of the ATP-modulated K’ channel in insulin-secreting cells. Biochem. Biophvs. Res. Commun., 146: 21–25.CrossRefGoogle Scholar
  37. Schmid-Antomarchi, H., De Weille, J. R., Fosset, M., and Lazdunski, M. 1987b. The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K’ channel in insulin-secreting cells. J. Biol. Chem., 262: 15840–15844.PubMedGoogle Scholar
  38. Spruce. A. E., Standen, N. B., and Stanfield, P. R. 1987. Studies of the unitary properties of adenosine 5’-Google Scholar
  39. triphosphate-regulated potassium channels of frog skeletal muscle. J. Phvsiol.,382:213–236.Google Scholar
  40. Trube, G., and Heschler, J. 1984. Inward-rectifying channels in isolated patches of the heart cell membrane:Google Scholar
  41. ATP-dependence and comparison with cell-attached patches. Pflügers Arch., 401:178–184.Google Scholar
  42. Zini, S., Tremblay, E., Roisin, M. P., and Ben Ari, Y. 1991. Two binding sites for [3H]glibenclamide in the rat brain. Brain Res., 542: 151–154.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Henri Bernardi
    • 1
  • Michel Lazdunski
    • 1
  1. 1.Institut de Pharmacologie Moléculaire et CellulaireCNRSSophia Antipolis, ValbonneFrance

Personalised recommendations