The Journal of Membrane Biology

, Volume 104, Issue 2, pp 165–177 | Cite as

The gating of nucleotide-sensitive K+ channels in insulin-secreting cells can be modulated by changes in the ratio ATP4−/ADP3− and by nonhydrolyzable derivatives of both ATP and ADP

  • M. J. Dunne
  • J. A. West-Jordan
  • R. J. Abraham
  • R. H. T. Edwards
  • O. H. Petersen
Articles

Summary

The31P-NMR technique has been used to assess the intracellular ratios and concentrations of mobile ATP and ADP and the intracellular pH in an insulin-secreting cell line, RINm5F. The single-channel current-recording technique has been used to investigate the effects of changes in the concentrations of ATP and ADP on the gating of nucleotide-dependent K+ channels. Adding ATP to the membrane inside closes these channels. However, in the continued presence of ATP adding ADP invariably leads to the reactivation of ATP-inhibited K+ channels, even at ATP4−/ADP3− concentration ratios greater than 7∶1. Interactions between ATP4− and ADP3− seem competitive. An increase in the concentration ratio ATP4−/ADP3− consistently evoked a decrease in the open-state probability of K+ channels; conversely a decrease in ATP4−/ADP3− increased the frequency of K+ channel opening events. Channel gating was also influenced by changes in the absolute concentrations of ATP4− and ADP3−, at constant free concentration ratios. ADP-evoked stimulation of ATP-inhibited channels did not result from phosphorylation of the channel, as ADP-β-S, a nonhydrolyzable analog of ADP, not only stimulated but enhanced ADP-induced activation of K+ channels, in the presence of ATP. Similarly, ADP was able to activate K+ channels in the presence of two nonhydrolyzable derivatives of ATP, AMP-PNP and βγmethylene ATP.

Key Words

K+ channel ATP ATP4− ADP3− RINm5F cell 

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References

  1. Ashcroft, S.J.H. 1980. Glucoreceptor mechanisms and the control of insulin release and biosynthesis.Diabetiologia 18:5–15Google Scholar
  2. Ashcroft, F.M., Ashcroft, S.J.H., Harrison, D.E. 1987. Effects of 2-ketoisocaproate on insulin release and single potassium channel activity in dispersed rat pancreatic beta-cells.J. Physiol. (London) 385:517–529Google Scholar
  3. Ashcroft, F.M., Harrison, D.E., Ashcroft, S.J.H. 1984. Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells.Nature (London) 312:446–448Google Scholar
  4. Ashcroft, F.M., Kakei, M. 1987. Effects of internal Mg2+ on ATP-sensitive K+ channels in isolated rat pancreatic B-cells.J. Physiol. (London) 390:72PGoogle Scholar
  5. Ashcroft, S.J.H., Weerasinghe, L.C.C., Randle, P.J. 1973. Interrelationship of islet metabolism, adenosine triphosphate content and insulin release.Biochem. J. 132:223–231Google Scholar
  6. Cook, D.L., Hales, C.N. 1984. Intracellular ATP directly blocks K+ channels in pancreatic B-cells.Nature (London) 311:271–273Google Scholar
  7. Dean, P.M., Matthews, E.K. 1970. Glucose-induced electrical activity in pancreatic islet cells.J. Physiol. (London) 210:255–264Google Scholar
  8. Dunne, M.J., Findlay, I., Petersen, O.H. 1988. The effects of pyridine nucleotides on the gating of ATP-sensitive K+ channels in insulin-secreting cells.J. Membrane Biol. 102:205–216Google Scholar
  9. Dunne, M.J., Findlay, I., Petersen, O.H., Wollheim, C.B. 1986. ATP-sensitive K+ channels in an insulin-secreting cell-line are inhibited byD-glyceraldehyde and activated by membrane permeabilization.J. Membrane Biol. 93:271–279Google Scholar
  10. Dunne, M.J., Ilott, M.C., Petersen, O.H. 1987. Interaction of diazoxide, tolbutamide and ATP4− on nucleotide-dependent K+ channels in an insulin-secreting cell line.J. Membrane Biol. 99:215–224Google Scholar
  11. Dunne, M.J., Petersen, O.H. 1986a. Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin-secreting cell line.FEBS Lett. 208:59–62Google Scholar
  12. Dunne, M.J., Petersen, O.H. 1986b. GTP and GDP activation of K+ channels that can be inhibited by ATP.Pfluegers Arch. 407:564–565Google Scholar
  13. Dunne, M.J., Petersen, O.H. 1987. Phorbol ester and cell-permeable diacylglycerol evoke closure of ATP-sensitive K+ channels in a cultured insulin-secreting cell-line.J. Physiol. (London) 390:73PGoogle Scholar
  14. Findlay, I. 1987. The effects of magnesium upon the ATP-sensitive K+ channel in an insulin-secreting cell line.J. Physiol. (London) 391:611–629Google Scholar
  15. Findlay, I., Dunne, M.J. 1986. ATP maintains ATP-inhibited K channels in an operational state.Pfluegers Arch. 407:238–240Google Scholar
  16. Findlay, I., Dunne, M.J., Petersen, O.H. 1985a. ATP-sensitive inward rectifier and voltage- and calcium-activated K+ channels in cultured pancreatic islet cells.J. Membrane Biol. 88:165–172Google Scholar
  17. Findlay, I., Dunne, M.J., Petersen, O.H. 1985b. High-conductance K+ channel in pancreatic islet cells can be activated and inactivated by internal calcium.J. Membrane Biol. 83:169–175Google Scholar
  18. Gadian, D.G. 1982. Nuclear Magnetic Resonance and Its Application to Living Systems. pp. 1–197. Clarendon, OxfordGoogle Scholar
  19. Gadian, D.G., Radda, G.K. 1981. NMR studies of tissue metabolism.Ann. Rev. Biochem. 50:69–83Google Scholar
  20. Halban, P.A., Praz, G.A., Wollheim, C.B. 1983. Abnormal glucose metabolism accompanies failure of glucose to stimulate insulin release from a pancreatic cell line (RINm5F).Biochem. J. 212:439–443Google Scholar
  21. Hamill, O.P., Marty, A., Neher, E., Sakmann, B., Sigworth, F.J. 1981. Improved patch-clamp techniques for high resolution current recordings from cells and cell-free membrane patches.Pfluegers Arch. 391:85–100Google Scholar
  22. Hedeskov, C.J. 1980. Mechanism of glucose-induced insulin secretion.Physiol. Rev. 60:442–509Google Scholar
  23. Hellman, B., Sehlin, J., Täljedal, I.B. 1972. The intracellular pH of mammalian pancreatic B-cells.Endocrinology 90:335–337Google Scholar
  24. Henquin, J.C., Meissner, H.P. 1984. Significance of ionic fluxes and changes in the membrane potential for stimulus-secretion coupling in pancreatic B-cells.Experientia 40:1043–1052Google Scholar
  25. Henquin, J.C., Tamagawa, T., Nenquin, M., Cogneau, M. 1983. Glucose modulates Mg2+ fluxes in pancreatic islet cells.Nature (London) 301:73–74Google Scholar
  26. Hoenig, M., Matschinsky, F.M. 1987. HPLC analysis of nucleotide profiles in glucose stimulated perfused rat islets.Metabolism 36:295–301Google Scholar
  27. Hutton, J.C., Sener, A., Herchuelz, A., Valverde, I., Boschero, A.C., Malaisse, W.J. 1980. The stimulus secretion coupling of glucose-induced insulin release. XLII. Effects of pH on insulin release. Their dependency on nutrient concentration.Horm. Met. Res. 12:285–348Google Scholar
  28. Kakei, M., Kelly, R.P., Ashcroft, S.J.H., Ashcroft, F.M. 1986. The ATP-sensitivity of K+ channels in rat pancreatic B-cells is modulated by ADP.FEBS Lett. 208:63–66Google Scholar
  29. Lebrun, P., Van Gasse, E., Juvent, M., Deleers, M., Herchuelz, A. 1986. Na+−H+ exchange in the process of glucose-induced insulin release from the pancreatic B-cell. Effects of amiloride on86Rb,45Ca fluxes and insulin release.Biochim. Biophys. Acta 886:448–456Google Scholar
  30. Malaisse, W.J., Hutton, J.C., Kawazu, S., Herchuelz, A., Valverde, I., Sener, A. 1979. The stimulus-secretion coupling of glucose-induced insulin release. XXXV. The links between metabolic and cationic events.Diabetologia 16:331–341Google Scholar
  31. Malaisse, W.J., Sener, A. 1987. Glucose-induced changes in cytosolic ATP content in pancreatic islets.Biochim. Biophys. Acta 927:190–195Google Scholar
  32. Malaisse, W.J., Sener, A., Boschero, A.C., Kawazu, S., Devis, G., Somers, G. 1978. The stimulus-secretion coupling of glucose-induced insulin release. Cationic and secretory effects of menadione in the endocrine pancreas.Eur. J. Biochem. 87:111–120Google Scholar
  33. Malaisse, W.J., Sener, A., Malaisse-Lagae, F., Welsh, M., Matthews, D.E., Bier, D.M., Hellerström, C. 1982. The stimulus-secretion coupling of amino acid-induced insulin release. Metabolic responses of pancreatic islets toL-glutamine andL-leucine.J. Biol. Chem. 257:8731–8737Google Scholar
  34. Martell, A.E., Smith, R.M. 1974. Critical Stability Constants. Vol. 1: Amino Acids. Plenum, New YorkGoogle Scholar
  35. Matthews, E.K., Sakamoto, Y. 1975. Electrical characteristics of pancreatic islet cells.J. Physiol. (London) 246:421–437Google Scholar
  36. Meglasson, M.D., Matschinsky, F.M. 1986. Pancreatic islet glucose metabolism and regulation of insulin release.Diabetes/Metabolism Rev. 2:163–214Google Scholar
  37. Meissner, H.P. 1976. Electrical characteristics of beta-cells in pancreatic islets.J. Physiol. (Paris) 72:757–767Google Scholar
  38. Misler, S., Falke, L.C., Gillis, K., McDaniel, M.L. 1986. A metabolite regulated potassium channel in rat pancreatic B-cells.Proc. Natl. Acad. Sci. USA 83:7119–7123Google Scholar
  39. Ohno-Shosaku, T., Zünkler, B.J., Trube, G. 1987. Dual effects of ATP on K+ currents in mouse pancreatic B-cells.Pfluegers Arch. 408:133–138Google Scholar
  40. Petersen, O.H., Findlay, I. 1987. Electrophysiology of the pancreas.Physiol. Rev. 67:1054–1116Google Scholar
  41. Ribalet, B., Ciani, S. 1987. Regulation by cell metabolism and adenosine nucleotides of a K+ channel in insulin secreting B-cells (RINm5F).Proc. Natl. Acad. Sci. USA 84:1721–1725Google Scholar
  42. Rorsman, P., Trube, G. 1985. Glucose-dependent K+ channels in pancreatic B-cells are regulated by intracellular ATP.Pfluegers Arch. 405:305–309Google Scholar
  43. Sener, A., Hutton, J.C., Kawazu, S., Boschero, A.C., Sommers, G., Devis, G., Herchuelz, A., Malaisse, W.J. 1978. The stimulus-secretion coupling of glucose induced insulin release. Metabolic and functional effects of NH4+ in rat islets.J. Clin. Invest. 62:868–878Google Scholar
  44. Sillen, L.G., Martell, A.E. 1971. Stability Constants of Metal-Ion Complexes. Spec. Publ. No. 25. Chemical Society of CanadaGoogle Scholar
  45. Squire, L.G., Petersen, O.H. 1987. Modulation of Ca2+- and voltage-activated K+ channels by internal Mg2+ in salivary acinar cells.Biochim. Biophys. Acta 899:171–175Google Scholar
  46. Stanfield, P.R. 1987. Nucleotides such as ATP may control the activity of ion channels.Trends Neurosci. 10:335–339Google Scholar
  47. Wollheim, C.B., Biden, T.J. 1987. Signal transduction in insulin secretion: Comparison between fuel stimuli and receptor agonists.Ann. N.Y. Acad. Sci. 488:317–333Google Scholar
  48. Wollheim, C.B., Dunne, M.J., Peter-Riesh, B., Brujjone, R., Pozzin, T., Petersen, O.M. 1988. Activators of protein kinase C depolarize insulin-secreting cells by closing K+ channels.EMBO J. (in press) Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1988

Authors and Affiliations

  • M. J. Dunne
    • 1
  • J. A. West-Jordan
    • 2
  • R. J. Abraham
    • 3
  • R. H. T. Edwards
    • 2
  • O. H. Petersen
    • 1
  1. 1.M.R.C. Secretory Control Research Group, The Physiological LaboratoryUniversity of LiverpoolLiverpoolEngland
  2. 2.The Department of MedicineUniversity of LiverpoolLiverpoolEngland
  3. 3.The Department of Organic ChemistryUniversity of LiverpoolLiverpoolEngland

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