Recombinant G-protein βγ-subunits activate the muscarinic-gated atrial potassium channel

作者: Kevin D. Wickman , Jorge A. Iñiguez-Lluhi , Philip A. Davenport , Ronald Taussig , Grigory B. Krapivinsky

DOI: 10.1038/368255A0

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摘要: Acetylcholine activates inwardly rectifying potassium channels (IK.ACh) in the heart through muscarinic receptor binding and activation of pertussis-toxin-sensitive G proteins. Experiments showing that only beta gamma-subunit (G gamma) IK.ACh (ref. 4) were challenged by reports activated alpha-subunit alpha) was effective. Here we examine regulation using purified brain recombinant G-protein subunits. Six gamma-subunits with apparent half-maximal concentrations 3-30 nM. Activation alpha-GTP gamma S observed, but this probably due to release GTP from protein. Importantly, activity elicited inhibited alpha-GDP, suggesting native plays a major role pathway. We conclude is primary regulator activity.

参考文章(15)
L Birnbaumer, G E Kirsch, J Codina, R Graf, K Okabe, J Olate, A M Brown, R Mattera, A Yatani, Recombinant αi-3 Subunit of G Protein Activates Gk-gated K+ Channels Journal of Biological Chemistry. ,vol. 264, pp. 465- 471 ,(1989) , 10.1016/S0021-9258(17)31281-4
Diomedes E. Logothetis, Yoshihisa Kurachi, Jonas Galper, Eva J. Neer, David E. Clapham, The βγ subunits of GTP-binding proteins activate the muscarinic K + channel in heart Nature. ,vol. 325, pp. 321- 326 ,(1987) , 10.1038/325321A0
M E Linder, I H Pang, R J Duronio, J I Gordon, P C Sternweis, A G Gilman, Lipid modifications of G protein subunits.: Myristoylation of Goα increases its affinity for βγ Journal of Biological Chemistry. ,vol. 266, pp. 4654- 4659 ,(1991) , 10.1016/S0021-9258(20)64372-1
M L Applebury, P C Sternweis, D J Roof, Relationships within the family of GTP-binding proteins isolated from bovine central nervous system. Journal of Biological Chemistry. ,vol. 260, pp. 16242- 16249 ,(1985) , 10.1016/S0021-9258(17)36227-0
P C Sternweis, J D Robishaw, Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain Journal of Biological Chemistry. ,vol. 259, pp. 13806- 13813 ,(1984) , 10.1016/S0021-9258(18)89817-9
J.A. Iñiguez-Lluhi, M.I. Simon, J.D. Robishaw, A.G. Gilman, G protein beta gamma subunits synthesized in Sf9 cells. Functional characterization and the significance of prenylation of gamma. Journal of Biological Chemistry. ,vol. 267, pp. 23409- 23417 ,(1992) , 10.1016/S0021-9258(18)50106-X
J Codina, A Yatani, D Grenet, A. Brown, L Birnbaumer, The alpha subunit of the GTP binding protein Gk opens atrial potassium channels. Science. ,vol. 236, pp. 442- 445 ,(1987) , 10.1126/SCIENCE.2436299
I. H. Pang, P. C. Sternweis, Isolation of the alpha subunits of GTP-binding regulatory proteins by affinity chromatography with immobilized beta gamma subunits. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 86, pp. 7814- 7818 ,(1989) , 10.1073/PNAS.86.20.7814