Vedovato Natascia, Ashcroft Frances M, Puljung Michael C
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Biophys J. 2015 Dec 15;109(12):2452-2460. doi: 10.1016/j.bpj.2015.10.026.
ATP-sensitive potassium (KATP) channels comprise four pore-forming Kir6.2 subunits and four modulatory sulfonylurea receptor (SUR) subunits. The latter belong to the ATP-binding cassette family of transporters. KATP channels are inhibited by ATP (or ADP) binding to Kir6.2 and activated by Mg-nucleotide interactions with SUR. This dual regulation enables the KATP channel to couple the metabolic state of a cell to its electrical excitability and is crucial for the KATP channel's role in regulating insulin secretion, cardiac and neuronal excitability, and vascular tone. Here, we review the regulation of the KATP channel by adenine nucleotides and present an equilibrium allosteric model for nucleotide activation and inhibition. The model can account for many experimental observations in the literature and provides testable predictions for future experiments.
ATP敏感性钾（KATP）通道由四个形成孔道的Kir6.2亚基和四个调节性磺脲类受体（SUR）亚基组成。后者属于ATP结合盒转运蛋白家族。KATP通道通过ATP（或ADP）与Kir6.2结合而被抑制，并通过镁核苷酸与SUR的相互作用而被激活。这种双重调节使KATP通道能够将细胞的代谢状态与其电兴奋性联系起来，对于KATP通道在调节胰岛素分泌、心脏和神经元兴奋性以及血管张力方面的作用至关重要。在此，我们综述了腺嘌呤核苷酸对KATP通道的调节作用，并提出了一个核苷酸激活和抑制的平衡变构模型。该模型可以解释文献中的许多实验观察结果，并为未来的实验提供可检验的预测。
