ASSOCIATION AND STOICHIOMETRY OF K-ATP CHANNEL SUBUNITS

ATP-sensitive potassium channels (K-ATP channels) are heteromultimers of sulfonylurea receptors (SUR) and inwardly rectifying potassium chan nel subunits (K(IR)6.x) with a (SUR-K(IR)6.x)(4) stoichiometry. Associ ation is specific for K(IR)6.x and affects receptor glycosylation and cophotolabeling of K(IR)6.x by I-125-azidoglibenclamide. Association p roduces digitonin stable complexes with an estimated mass of 950 kDa. These complexes can be purified by lectin chromatography or by using N i2+-agarose and a his-tagged SUR1. Expression of SUR1 similar to(K(IR) 6.2), fusion constructs shows that a 1:1 SUR1:K(IR)6.2 stoichiometry i s both necessary and sufficient for assembly of active K-ATP channels. Coexpression of a mixture of strongly and weakly rectifying triple fu sion proteins, rescued by SUR1, produced the three channel types expec ted of a tetrameric pore.