Molecular structure of the K_ATP channel. (A) Schematic representation of the transmembrane topology of a single SURx (left) or Kir6.x (right) subunit. Mg-nucleotide binding/hydrolysis at the nucleotide-binding domains (NBD1, NBD2) of SUR stimulates channel activity. Sulfonylureas (stimulatory) and K channel openers (inhibitory) also bind to SUR1. Binding of _ATP or ADP to Kir6.2 closes the pore, an effect that does not require Mg²⁺. Conversely, binding of phospholipids such as PIP2, or long-chain (LC) acyl-coAs, stimulates K_ATP channel activity and decreases its _ATP sensitivity. (B) Schematic representation of the octameric K_ATP channel complex viewed in cross section. Four Kir6.2 subunits come together to form the pore through which K⁺ ions move, and each is associated with a regulatory SURx subunit. (C) Model of how SUR1 and Kir6.2 might assemble to form the K_ATP channel. The SUR model is described in ref. 115 and the Kir6.2 model in ref. 116. The model illustrates that the channel complex contains 4 _ATP-binding sites (on Kir6.2) and 8 Mg nucleotide–binding sites (on SUR1).