A VIEW OF SUR K(IR)6.X, K-ATP CHANNELS

ATP-sensitive potassium channels, termed K-ATP channels, link the elec trical activity of cell membranes to cellular metabolism. These channe ls are heteromultimers of sulfonylurea receptor (SUR) and K(IR)6.x sub units associated with a 1:1 stoichiometry as a tetramer (SUR/K(IR)6.x) (4). K(IR)6.x forms the pores, whereas SUR regulates their activity. C hanges in [ATP](i) and [ADP](i) gate the channel. The diversity of K-A TP channels results from the assembly of SUR and K(IR)6.x subtypes. K( IR)6.1-based channels differ from K(IR)6.2 channels mainly by their sm aller unitary conductance. SUR1- and SUR2-based channels are distingui shed by their differential sensitivity to sulfonylureas, whereas SUR2A -based channels are distinguished from SUR2B channels by their differe ntial sensitivity to diazoxide. Mutations that result in the loss of K -ATP channels in pancreatic beta-cells have been identified in SUR1 an d K(IR)6.2. These mutations lead to familial hyperinsulinism. Understa nding the mutations in SUR and K(IR)6.x is allowing insight into how t hese channels respond to nucleotides, sulfonylureas, and potassium cha nnel openers, KCOs.