Khan R N, Hales C N, Ozanne S E, Adogu A A, Ashford M L
Department of Pharmacology, University of Cambridge, U.K.
Proc Biol Sci. 1993 Sep 22;253(1338):225-31. doi: 10.1098/rspb.1993.0107.
It is generally considered that the sulphonylurea receptor is an integral part of the ATP-sensitive K+ channel. We have investigated this proposal by comparing the binding and functional characteristics of the sulphonylurea receptor and KATP channel by using two rat insulinoma cell lines (CRI-G1 and CRI-D11) of common origin. Insulin release was increased in both cell lines by a variety of metabolizable and non-metabolizable secretagogues but glibenclamide induced an increase in insulin release in G1 cells only. [3H]glibenclamide binding studies showed a substantial reduction in the number of glibenclamide binding sites (Bmax) in the D11 cells compared with G1 cells. Single-channel studies of these cell lines show that the KATP channel is generally unchanged in its biophysical properties and in the number of channels observed. Slight differences were apparent: the KATP channels in D11 cells were much less susceptible to rundown and were slightly less sensitive to block by ATP. However, one major distinction was the lack or much reduced sensitivity of the KATP channel in D11 cells to tolbutamide and glibenclamide. We conclude that the KATP channel can exist and function independently of the sulphonylurea receptor, and therefore it is unlikely that they exist as a single protein assembly.
一般认为磺脲类受体是ATP敏感性钾通道的一个组成部分。我们通过使用两个源自同一亲本的大鼠胰岛素瘤细胞系（CRI-G1和CRI-D11），比较磺脲类受体和KATP通道的结合及功能特性，对这一观点进行了研究。多种可代谢和不可代谢的促分泌剂均可使这两种细胞系的胰岛素释放增加，但格列本脲仅能使G1细胞的胰岛素释放增加。[3H]格列本脲结合研究显示，与G1细胞相比，D11细胞中格列本脲结合位点的数量（Bmax）大幅减少。对这些细胞系进行的单通道研究表明，KATP通道的生物物理特性和所观察到的通道数量总体上没有变化。有一些细微差异很明显：D11细胞中的KATP通道不太容易出现电流衰减，对ATP阻断的敏感性也略低。然而，一个主要区别是D11细胞中的KATP通道对甲苯磺丁脲和格列本脲缺乏敏感性或敏感性大幅降低。我们得出结论，KATP通道可以独立于磺脲类受体而存在并发挥功能，因此它们不太可能以单一蛋白质复合体的形式存在。
