Abstract
K(ATP) channels are hetero-octameric complexes of four inward rectifying potassium channels, Kir6.1 or Kir6.2, and four sulfonylurea receptors, SUR1, SUR2A, or SUR2B from the ABC transporter family. This unique combination enables K(ATP) channels to couple intracellular ATP/ADP ratios, through gating, with membrane excitability, thus regulating a broad range of cellular activities. The prominence of K(ATP) channels in human physiology, disease, and pharmacology has long attracted research interest. Since 2017, a steady flow of high-resolution K(ATP) cryoEM structures has revealed complex and dynamic interactions between channel subunits and their ligands. Here, we highlight insights from recent structures that begin to provide mechanistic explanations for decades of experimental data and discuss the remaining knowledge gaps in our understanding of K(ATP) channel regulation.