Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
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DOI：
10.1038/387179a0
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发表时间：
1997-05-08
期刊：
影响因子：
64.8
通讯作者：
Ashcroft, FM
中科院分区：
文献类型：
--
作者：
Tucker, SJ;Gribble, FM;Ashcroft, FM
ATP 敏感钾通道（K-ATP 通道）将细胞代谢与电活动耦合起来，在许多组织的生理学和病理生理学中非常重要(1)。在胰腺 β 细胞中，K-ATP 通道将血糖浓度的变化与胰岛素分泌联系起来 (2)。它们也是临床重要药物的靶标，例如刺激分泌的磺脲类药物和抑制胰岛素释放的 K+ 通道开放剂二氮嗪 (3,4)。 K-ATP 通道的代谢调节是通过细胞内 ATP 和 Mg-ADP 水平的变化介导的，这分别抑制和激活该通道 (2)。 β 细胞 K-ATP 通道是两种蛋白质 (5,6) 的复合体：内向整流 K+ 通道亚基 Kir6.2 和磺酰脲受体 SUR1。我们在此表明，ATP 介导 K-ATP 通道抑制的主要位点位于 Kir6.2，并且 SUR1 是对磺脲类和二氮嗪敏感以及 Mg-ADP 激活所必需的。
ATP-sensitive potassium channels (K-ATP channels) couple cell metabolism to electrical activity and are important in the physiology and pathophysiology of many tissues(1). In pancreatic beta-cells, K-ATP channels Link changes in blood glucose concentration to insulin secretion(2). They are also the target for clinically important drugs such as sulphonylureas, which stimulate secretion, and the K+ channel opener diazoxide, which inhibits insulin release(3,4). Metabolic regulation of K-ATP channels is mediated by changes in intracellular ATP and Mg-ADP levels, which inhibit and activate the channel, respectively(2). The beta-cell K-ATP channel is a complex of two proteins(5,6): an inward-rectifier K+ channel subunit, Kir6.2, and the sulphonylurea receptor, SUR1. We show here that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP.