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.

K _ATP通道是四个内向整流钾通道 Kir6.1 或 Kir6.2 以及来自 ABC 转运蛋白家族的四个磺酰脲受体 SUR1、SUR2A 或 SUR2B 的异八聚体复合物。这种独特的组合使 K _ATP通道能够通过门控与膜兴奋性耦合细胞内 ATP/ADP 比率，从而调节广泛的细胞活动。 K _ATP通道在人类生理学、疾病和药理学中的突出地位长期以来引起了人们的研究兴趣。自 2017 年以来，稳定的高分辨率 K _ATP冷冻电镜结构揭示了通道亚基及其配体之间复杂且动态的相互作用。在这里，我们重点介绍最近结构的见解，这些结构开始为数十年的实验数据提供机械解释，并讨论我们对 K _ATP通道调节的理解中剩余的知识差距。