Diabetes, Vol 37, Issue 5 495-498, Copyright © 1988 by American Diabetes Association

ARTICLES

ATP-sensitive K+ channels in pancreatic beta-cells. Spare-channel hypothesis

DL Cook, LS Satin, ML Ashford and CN Hales
Department of Medicine, University of Washington, Seattle.

Since their discovery in pancreatic beta-cells, ATP-sensitive K+ channels in the cell membrane have been thought to mediate glucose-induced beta-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 beta-cell, the extreme sensitivity of the channels to ATP is appropriate and even mandatory for their physiological function.
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