磺脲类受体家族决定ATP敏感性钾通道的药理特性。

A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.

作者信息

Inagaki N, Gonoi T, Clement J P, Wang C Z, Aguilar-Bryan L, Bryan J, Seino S

机构信息

Division of Molecular Medicine Center for Biomedical Science, Chiba University School of Medicine, Chuo-ku, Chiba 260, Japan.

出版信息

Neuron. 1996 May;16(5):1011-7. doi: 10.1016/s0896-6273(00)80124-5.

DOI:10.1016/s0896-6273(00)80124-5

PMID:8630239

Abstract

We have cloned an isoform of the sulfonylurea receptor (SUR), designated SUR2. Coexpression of SUR2 and the inward rectifier K+ channel subunit Kir6.2 in COS1 cells reconstitutes the properties of K(ATP) channels described in cardiac and skeletal muscle. The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic beta cell KATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac K(ATP) channel openers, cromakalim and pinacidil, but not by diazoxide. In addition, SUR2 binds glibenclamide with lower affinity. The present study shows that the ATP sensitivity and pharmacological properties of K(ATP) channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors.

摘要

我们克隆了磺脲类受体（SUR）的一种同工型，命名为SUR2。SUR2与内向整流钾通道亚基Kir6.2在COS1细胞中共表达，可重建心肌和骨骼肌中所描述的K(ATP)通道特性。SUR2/Kir6.2通道对ATP和磺脲类药物格列本脲的敏感性低于SUR/Kir6.2通道（胰腺β细胞KATP通道），并可被心脏K(ATP)通道开放剂克罗卡林和吡那地尔激活，但不能被二氮嗪激活。此外，SUR2与格列本脲的结合亲和力较低。本研究表明，K(ATP)通道的ATP敏感性和药理特性由一组结构相关但功能不同的磺脲类受体决定。