Neuron
Volume 16, Issue 5, May 1996, Pages 1011-1017
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Article
A Family of Sulfonylurea Receptors Determines the Pharmacological Properties of ATP-Sensitive K+ Channels

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Abstract

We have cloned an isoform of the sulfonylurea receptor (SUR), designated SUR2. Coexpression of SUR2 and the inward rectifier K+ channel subunit Kir6.2 in COS1 cells reconstitutes the properties of KATP channels described in cardiac and skeletal muscle. The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic β cell KATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac KATP channel openers, cromakalim and pinacidil, but not by diazoxide. In addition, SUR2 binds glibenclamide with lower affinity. The present study shows that the ATP sensitivity and pharmacological properties of KATP channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors.

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