FUNCTIONAL AND MOLECULAR DISTINCTION BETWEEN RECOMBINANT RAT GABA-A RECEPTOR SUBTYPES BY ZN-2+

被引:386
作者
DRAGUHN, A [1 ]
VERDORN, TA [1 ]
EWERT, M [1 ]
SEEBURG, PH [1 ]
SAKMANN, B [1 ]
机构
[1] UNIV HEIDELBERG,CTR MOLEC BIOL,MOLEC NEUROENDOCRINOL LAB,W-6900 HEIDELBERG,GERMANY
关键词
D O I
10.1016/0896-6273(90)90337-F
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:781 / 788
页数:8
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