ATP-sensitive K+ channels in pancreatic β-cells: Spare-channel hypothesis

Daniel L. Cook, Leslie S. Satin, Michael L. J. Ashford, C. Nicholas Hales

    Research output: Contribution to journalArticlepeer-review

    226 Citations (Scopus)


    Since their discovery in pancreatic ß-cells, ATP-sensitive K+ channels in the cell membrane have been thought to mediate glucose-induced ß-cell depolarization, which is required for triggering the voltage-dependent Ca2+ uptake subserving insulin release. The theory is that metabolism of glucose (and other fuel molecules) increases intracellular ATP or possibly other metabolites that diffuse to the membrane and inhibit the opening of ATP-sensitive K+ channels. This slows the efflux of positively charged K+ and depolarizes the cell. A recurrent source of confusion regarding this idea stems from the early observation that these channels are so exquisitely sensitive to intracellular ATP that channel opening is predicted to be approximately 99% inhibited under physiological conditions. To account for this apparent discrepancy, various mechanisms have been proposed that might render the channels less sensitive to intracellular ATP. We use a simple mathematical model to demonstrate that there is no major discrepancy and that, in fact, given the electrophysiological mechanisms existing in the ß-cell, the extreme sensitivity of the channels to ATP is appropriate and even mandatory for their physiological function.

    Original languageEnglish
    Pages (from-to)495-498
    Number of pages4
    Issue number5
    Publication statusPublished - May 1988


    • Humans
    • Ion Channels
    • Glucose
    • Membrane Potentials
    • Islets of Langerhans
    • Electrophysiology
    • Adenosine Triphosphate


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