A VIEW OF SUR/KIR6.X, KATP CHANNELS

▪ Abstract ATP-sensitive potassium channels, termed K ATP channels, link the electrical activity of cell membranes to cellular metabolism. These channels are heteromultimers of sulfonylurea receptor (SUR) and K IR 6.x subunits 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. Changes in [ATP] i and [ADP] i gate the channel. The diversity of K ATP 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 smaller unitary conductance. SUR1- and SUR2-based channels are distinguished by their differential sensitivity to sulfonylureas, whereas SUR2A-based channels are distinguished from SUR2B channels by their differential sensitivity to diazoxide. Mutations that result in the loss of K ATP channels in pancreatic β-cells have been identified in SUR1 and K IR 6.2. These mutations lead to familial hyperinsulinism. Understanding the mutations in SUR and K IR 6.x is allowing insight into how these channels respond to nucleotides, sulfonylureas, and potassium channel openers, KCOs.