Krapivinsky G, Krapivinsky L, Velimirovic B, Wickman K, Navarro B, Clapham D E
Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905, USA.
J Biol Chem. 1995 Dec 1;270(48):28777-9. doi: 10.1074/jbc.270.48.28777.
Cardiac IKACh is comprised of two inwardly rectifying K+ channel subunits, CIR and GIRK1 (Krapivinsky, G., Gordon, E. G., Wickman, K., Velimirovic, B., Krapivinsky, L., and Clapham, D. E. (1995) Nature 374, 135-141). A cardiac protein virtually identical to CIR, termed rcKATP-1 (Ashford, M. L. J., Bond, C. T., Blair, T. A., and Adelman, J. P. (1994) Nature 370, 456-459), was reported to form an ATP-sensitive inwardly rectifying K+ channel, IKATP. We attempted to determine whether CIR alone or together with an unknown protein(s) participated in the formation of cardiac IKATP. Expression of CIR in insect, oocyte, and mammalian cell systems did not increase the appearance of ATP-sensitive currents, but rather gave rise to unique strongly inwardly rectifying, G protein-regulated K+ currents. CIR protein is found exclusively in atria, in contrast to the predominance of IKATP functional activity in ventricle. Also, CIR was completely depleted from heart membrane after immunodepletion of GIRK1. We conclude that CIR/rcKATP-1 is not a subunit of cardiac IKATP and that GIRK1 is the only channel protein coassociating with CIR in heart.
心脏内向整流钾通道（IKACh）由两个内向整流钾离子通道亚基组成，即内向整流钾通道（CIR）和G蛋白偶联内向整流钾通道1（GIRK1）（克拉皮温斯基，G.，戈登，E.G.，维克曼，K.，韦利米罗维奇，B.，克拉皮温斯基，L.，和克拉彭，D.E.（1995年）《自然》374卷，第135 - 141页）。一种与CIR几乎完全相同的心脏蛋白，称为rcKATP - 1（阿什福德，M.L.J.，邦德，C.T.，布莱尔，T.A.，和阿德尔曼，J.P.（1994年）《自然》370卷，第456 - 459页），据报道它能形成一种对ATP敏感的内向整流钾通道，即ATP敏感性钾通道（IKATP）。我们试图确定单独的CIR还是与一种未知蛋白质一起参与了心脏IKATP的形成。在昆虫、卵母细胞和哺乳动物细胞系统中表达CIR并没有增加对ATP敏感电流的出现，反而产生了独特的、强烈内向整流的、G蛋白调节的钾电流。与IKATP功能活性在心室中占主导不同，CIR蛋白仅在心房中发现。此外，在免疫去除GIRK1后，心脏膜中CIR完全耗尽。我们得出结论，CIR/rcKATP - 1不是心脏IKATP的亚基，并且GIRK1是心脏中与CIR共同结合的唯一通道蛋白。
