Seino Susumu, Miki Takashi
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8760, Japan.
Prog Biophys Mol Biol. 2003 Feb;81(2):133-76. doi: 10.1016/s0079-6107(02)00053-6.
ATP-sensitive potassium (K(ATP)) channels are present in many tissues, including pancreatic islet cells, heart, skeletal muscle, vascular smooth muscle, and brain, in which they couple the cell metabolic state to its membrane potential, playing a crucial role in various cellular functions. The K(ATP) channel is a hetero-octamer comprising two subunits: the pore-forming subunit Kir6.x (Kir6.1 or Kir6.2) and the regulatory subunit sulfonylurea receptor SUR (SUR1 or SUR2). Kir6.x belongs to the inward rectifier K(+) channel family; SUR belongs to the ATP-binding cassette protein superfamily. Heterologous expression of differing combinations of Kir6.1 or Kir6.2 and SUR1 or SUR2 variant (SUR2A or SUR2B) reconstitute different types of K(ATP) channels with distinct electrophysiological properties and nucleotide and pharmacological sensitivities corresponding to the various K(ATP) channels in native tissues. The physiological and pathophysiological roles of K(ATP) channels have been studied primarily using K(ATP) channel blockers and K(+) channel openers, but there is no direct evidence on the role of the K(ATP) channels in many important cellular responses. In addition to the analyses of naturally occurring mutations of the genes in humans, determination of the phenotypes of mice generated by genetic manipulation has been successful in clarifying the function of various gene products. Recently, various genetically engineered mice, including mice lacking K(ATP) channels (knockout mice) and mice expressing various mutant K(ATP) channels (transgenic mice), have been generated. In this review, we focus on the physiological and pathophysiological roles of K(ATP) channels learned from genetic manipulation of mice and naturally occurring mutations in humans.
ATP敏感性钾（K(ATP)）通道存在于许多组织中，包括胰岛细胞、心脏、骨骼肌、血管平滑肌和大脑，在这些组织中，它们将细胞代谢状态与其膜电位联系起来，在各种细胞功能中发挥关键作用。K(ATP)通道是一种异源八聚体，由两个亚基组成：形成孔道的亚基Kir6.x（Kir6.1或Kir6.2）和调节亚基磺脲类受体SUR（SUR1或SUR2）。Kir6.x属于内向整流钾（K(+)）通道家族；SUR属于ATP结合盒蛋白超家族。Kir6.1或Kir6.2与SUR1或SUR2变体（SUR2A或SUR2B）的不同组合的异源表达重构了具有不同电生理特性以及与天然组织中各种K(ATP)通道相对应的核苷酸和药理学敏感性的不同类型的K(ATP)通道。K(ATP)通道的生理和病理生理作用主要通过使用K(ATP)通道阻滞剂和K(+)通道开放剂进行研究，但在许多重要细胞反应中，尚无关于K(ATP)通道作用的直接证据。除了分析人类基因的自然突变外，通过基因操作产生的小鼠表型的确定已成功阐明了各种基因产物的功能。最近，已经产生了各种基因工程小鼠，包括缺乏K(ATP)通道的小鼠（基因敲除小鼠）和表达各种突变K(ATP)通道的小鼠（转基因小鼠）。在本综述中，我们重点关注从小鼠的基因操作和人类的自然突变中学到的K(ATP)通道的生理和病理生理作用。
