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K_ATP channels are ligand-gated potassium channels that couple cellular energetics with membrane potential to regulate a broad range of cell activities. Each channel is composed of four inward rectifying potassium channels, Kir6.1 or Kir6.2, which form the ion-conducting pore, and four regulatory sulfonylurea receptors, SUR1, SUR2A, or SUR2B, from the ABC transporter family. Mutations in K_ATP channels underlie several human diseases. The importance of these channels in human health and disease has made them attractive drug targets. Recent high-resolution K_ATP cryoEM structures have revealed complex and dynamic interactions between channel subunits and their ligands. The mechanistic insights from these structures offer opportunities to improve K_ATP pharmacology for disorders caused by channel dysfunction.