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

J Membr Biol. 1988 Sep;104(2):165-77. doi: 10.1007/BF01870928.

Abstract

The 31P-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-beta-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 beta gamma methylene ATP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives
  • Adenosine Diphosphate / pharmacology
  • Adenosine Diphosphate / physiology*
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / physiology*
  • Cell Line
  • Glyceraldehyde / pharmacology
  • Hydrogen-Ion Concentration
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / analysis
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / ultrastructure
  • Magnetic Resonance Spectroscopy / methods
  • Membrane Potentials / drug effects
  • Nucleotides / analysis
  • Nucleotides / pharmacology*
  • Phosphorylation
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Potassium Channels / ultrastructure
  • Thionucleotides / pharmacology

Substances

  • Insulin
  • Nucleotides
  • Potassium Channels
  • Thionucleotides
  • adenosine 5'-O-(2-thiodiphosphate)
  • Glyceraldehyde
  • Adenosine Diphosphate
  • Adenosine Triphosphate