Separate processes mediate nucleotide-induced inhibition and stimulation of the ATP-regulated K+-channels in mouse pancreatic β-cells

K. Bokvist, C. Ammala, F. M. Ashcroft, P. O. Berggren, O. Larsson, P. Rorsman

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

The mechanisms by which nucleotides stimulate the activity of the ATP-regulated K+-channel (K(ATP)-channel) were investigated using inside-out patches from mouse pancreatic β-cells. ATP produces a concentration-dependent inhibition of channel activity with a K(i) of 18 μM. The inhibitory action of ATP was counteracted by ADP (0.1 mM) and GDP (0.2 mM) but not GTP (1 mM). Stimulation of channel activity was also observed when ADP, GDP and GTP were applied in the absence of ATP. The ability of ADP and GDP to reactivate K(ATP)-channels blocked by ATP declined with time following patch excision and after 30-60 min these nucleotides were without effect. During the same time period the ability of ADP and GTP to stimulate the channel in the absence of ATP was lost. In fact, ADP now blocked channel activity with 50% inhibition being observed at approximately 0.1 mM. By contrast, GDP remained a stimulator in the absence of ATP even when its ability to evoke channel activity in the presence of ATP was lost. These observations show that nucleotide-induced activation of the K(ATP)-channel does not involve competition with ATP for a common inhibitory site but involves other processes. The data are consistent with the idea that nucleotides modulate K(ATP)-channel activity by a number of different mechanisms that may include both regulation of cytosolic constituents and direct interaction with the channel and associated control proteins.

Original languageEnglish (US)
Pages (from-to)139-144
Number of pages6
JournalProceedings of the Royal Society B: Biological Sciences
Volume243
Issue number1307
DOIs
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

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