KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit
KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit
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DOI：
10.1073/pnas.95.23.13953
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发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
Wang, J
中科院分区：
文献类型：
--
作者：
Drain, P;Li, LH;Wang, J
ATP敏感的钾（K-ATP）通道被细胞内ATP迅速抑制。这种抑制在多种细胞的电活动与能量代谢的耦合中起着至关重要的作用。K- atp通道由四个磺酰脲受体（SUR）调控亚基和一个向内整流钾（K(ir)6.2）成孔提交体组成。我们采用系统嵌合和点诱变技术，结合膜片钳记录，研究了atp依赖性抑制门控小鼠胰腺β细胞K-ATP通道在非洲爪蟾卵母细胞中的表达的分子基础。我们确定了K(ir)6.2亚基的细胞质c端段的不同功能域，这些功能域在这种抑制中起重要作用。我们的结果表明，一个结构域与抑制性ATP结合有关，另一个与门关闭有关。
ATP-sensitive potassium ("K-ATP") channels are rapidly inhibited bg intracellular ATP. This inhibition plays a crucial role in the coupling of electrical activity to energy metabolism in a variety of cells. The K-ATP channel is formed from four each of a sulfonylurea receptor (SUR) regulatory subunit and an inwardly rectifying potassium (K(ir)6.2) pore-forming submit. We used systematic chimeric and point mutagenesis, combined with patch-clamp recording, to investigate the molecular basis of ATP-dependent inhibition gating of mouse pancreatic beta cell K-ATP channels expressed in Xenopus oocytes. We identified distinct functional domains of the presumed cytoplasmic C-terminal segment of the K(ir)6.2 subunit that play an important role in this inhibition. Our results suggest that one domain is associated with inhibitory ATP binding and another with gate closure.