Dissociation of KATP channel and sulphonylurea receptor in the rat clonal insulin-secreting cell line, CRI-D11

R N Khan, C N Hales, S E Ozanne, A A Adogu, M. L. J. Ashford

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    It is generally considered that the sulphonylurea receptor is an integral part of the ATP-sensitive K+ channel. We have investigated this proposal by comparing the binding and functional characteristics of the sulphonylurea receptor and KATP channel by using two rat insulinoma cell lines (CRI-G1 and CRI-D11) of common origin. Insulin release was increased in both cell lines by a variety of metabolizable and non-metabolizable secretagogues but glibenclamide induced an increase in insulin release in G1 cells only. [3H]glibenclamide binding studies showed a substantial reduction in the number of glibenclamide binding sites (Bmax) in the D11 cells compared with G1 cells. Single-channel studies of these cell lines show that the KATP channel is generally unchanged in its biophysical properties and in the number of channels observed. Slight differences were apparent: the KATP channels in D11 cells were much less susceptible to rundown and were slightly less sensitive to block by ATP. However, one major distinction was the lack or much reduced sensitivity of the KATP channel in D11 cells to tolbutamide and glibenclamide. We conclude that the KATP channel can exist and function independently of the sulphonylurea receptor, and therefore it is unlikely that they exist as a single protein assembly.
    Original languageEnglish
    Pages (from-to)225-231
    Number of pages7
    JournalProceedings of the Royal Society B
    Volume253
    Issue number1338
    DOIs
    Publication statusPublished - 1993

    Keywords

    • Clone Cells
    • Glyburide
    • Animals
    • Tetradecanoylphorbol Acetate
    • 1-Methyl-3-isobutylxanthine
    • Pancreatic Neoplasms
    • Insulinoma
    • Potassium
    • Insulin
    • Potassium Channels
    • Rats
    • Tumor Cells, Cultured
    • Receptors, Drug
    • Potassium Channels, Inwardly Rectifying
    • Cell Membrane
    • ATP-Binding Cassette Transporters
    • Membrane Potentials
    • Tolbutamide
    • Adenosine Triphosphate

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