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Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor

Abstract

ATP-sensitive potassium channels (K-ATP channels) couple cell metabolism to electrical activity and are important in the physiology and pathophysiology of many tissues1. In pancreatic β-cells, K-ATP channels link changes in blood glucose concentration to insulin secretion2. They are also the target for clinically important drugs such as sulphonylureas, which stimulate secretion, and the K+ channel opener diazoxide, which inhibits insulin release3,4. Metabolic regulation of K-ATP channels is mediated by changes in intracellular ATP and Mg-ADP levels, which inhibit and activate the channel, respectively2. The β-cell K-ATP channel is a complex of two proteins5,6: an inward-rectifier K+ channel subunit, Kir6.2, and the sulphonylurea receptor, SUR1. We show here that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP.

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References

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Tucker, S., Gribble, F., Zhao, C. et al. Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor. Nature 387, 179–183 (1997). https://doi.org/10.1038/387179a0

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