ATP-sensitive potassium channels (KATP channels) are heteromultimers of sulfonylurea receptors (SUR) and inwardly rectifying potassium channel subunits (KIR6.x) with a (SUR–KIR6.x)4 stoichiometry. Association is specific for KIR6.x and affects receptor glycosylation and cophotolabeling of KIR6.x by 125I-azidoglibenclamide. Association produces digitonin stable complexes with an estimated mass of 950 kDa. These complexes can be purified by lectin chromatography or by using Ni2+–agarose and a his-tagged SUR1. Expression of SUR1∼(KIR6.2)i fusion constructs shows that a 1:1 SUR1:KIR6.2 stoichiometry is both necessary and sufficient for assembly of active KATP channels. Coexpression of a mixture of strongly and weakly rectifying triple fusion proteins, rescued by SUR1, produced the three channel types expected of a tetrameric pore.
