FUNCTIONAL AND MOLECULAR DISTINCTION BETWEEN RECOMBINANT RAT GABA-A RECEPTOR SUBTYPES BY ZN-2+
FUNCTIONAL AND MOLECULAR DISTINCTION BETWEEN RECOMBINANT RAT GABA-A RECEPTOR SUBTYPES BY ZN-2+
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DOI：
10.1016/0896-6273(90)90337-f
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发表时间：
1990-12-01
期刊：
影响因子：
16.2
通讯作者：
SAKMANN, B
中科院分区：
文献类型：
--
作者：
DRAGUHN, A;VERDORN, TA;SAKMANN, B
不同神经元中的γ-氨基丁酸受体(GABA(A)R)通道具有不同的功能特性。分子克隆揭示了大量的GABA(A)R亚基组装成具有不同功能特性的GABA(A)R亚型，提示亚基组合决定了受体的功能特性。在本研究中，GABA(A)Rs的亚基组成与锌敏感和锌不敏感受体亚型之间的功能差异有关。瞬时转基因成纤维细胞中重组的GABA(A)受体由编码α和β亚基的cDNA组合组成，被锌离子有效地阻断。伽马亚基与其他亚基的任何结合都会导致GABA(A)Rs的形成，而GABA(A)Rs对锌离子几乎不敏感。这些数据提供了与天然膜中锌离子对GABA(A)受体作用的功能异质性的结构关联，并表明锌离子对GABA激活电流的不敏感性表明在组装的GABA(A)R通道中存在一个伽玛亚基。
Gamma-Aminobutyric acid receptor (GABA(A)R) channels in different neurons display heterogeneous functional properties. Molecular cloning revealed a large number of GABA(A)R subunits that assemble into GABA(A)R subtypes with different functional properties, suggesting that the subunit combination determines the functional properties of the receptor. In this study, the subunit composition of GABA(A)Rs is related to a functional distinction between Zn2+-sensitive and Zn2+-insensitive receptor subtypes. GABA(A)Rs reconstituted in transiently transfected fibroblasts from combinations of cDNAs encoding alpha and beta subunits are potently blocked by Zn2+. The presence of a gamma subunit in any combination with the other subunits leads to the formation of GABA(A)Rs that are almost insensitive to Zn2+. These data provide a structural correlate to the functional heterogeneity of the action of Zn2+ on GABA(A)Rs in native membranes and show that Zn2+ insensitivity of GABA-activated currents indicates the presence of a gamma-subunit in the assembled GABA(A)R channel.