ATP-sensitive potassium (KATP) channels are uniquely evolved protein complexes that couple cell energy levels to cell excitability. They govern a wide range of physiological processes including hormone secretion, neuronal transmission, vascular dilation, and cardiac and neuronal preconditioning against ischemic injuries. In pancreatic β-cells, KATP channels composed of Kir6.2 and SUR1, encoded by KCNJ11 and ABCC8, respectively, play a key role in coupling blood glucose concentration to insulin secretion. Mutations in ABCC8 or KCNJ11 that diminish channel function result in congenital hyperinsulinism. Many of these mutations principally hamper channel biogenesis and hence trafficking to the cell surface. Several small molecules have been shown to correct channel biogenesis and trafficking defects. Here, we review studies aimed at understanding how mutations impair channel biogenesis and trafficking and how pharmacological ligands overcome channel trafficking defects, particularly highlighting recent cryo-EM structural studies which have shed light on the mechanisms of channel assembly and pharmacological chaperones.

中文翻译：

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ATP敏感钾通道的药理伴侣：来自cryoEM结构的机理见解。

ATP敏感性钾（KATP）通道是独特进化的蛋白质复合物，可将细胞能量水平与细胞兴奋性结合起来。它们控制着广泛的生理过程，包括激素分泌，神经元传递，血管扩张以及针对缺血性损伤的心脏和神经元预处理。在胰腺β细胞中，分别由KCNJ11和ABCC8编码的由Kir6.2和SUR1组成的KATP通道在将血糖浓度与胰岛素分泌耦合中起关键作用。ABCC8或KCNJ11中削弱通道功能的突变会导致先天性高胰岛素血症。这些突变中的许多主要阻碍通道的生物发生，因此阻碍了其向细胞表面的运输。已经显示出几种小分子可以纠正通道的生物发生和运输缺陷。这里，