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


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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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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