Saxena N C, Macdonald R L
Department of Neurology, University of Michigan Medical School, Ann Arbor 48109-1687.
J Neurosci. 1994 Nov;14(11 Pt 2):7077-86. doi: 10.1523/JNEUROSCI.14-11-07077.1994.
GABAA receptor channels (GABARs) composed of different combinations of rat alpha 1, beta 1, gamma 2L, and delta subunits were expressed transiently in mouse fibroblast cells (L929 cells). Whole-cell recordings were obtained from transfected cells to determine which combinations of GABAR subunits formed functional receptor channels, and to compare the electrophysiological and pharmacological characteristics of GABAR channels expressed in the presence and absence of the delta subunit. Only alpha 1 beta 1 gamma 2L, alpha 1 beta 1 gamma 2L delta, and alpha 1 beta 1 delta subunit combinations assembled to form functional GABAR channels and the presence of the delta-subunit slowed the rate of acute desensitization of GABA-evoked current during GABA application and the rate of recovery of GABA-evoked current following GABA application. These three different GABAR channel isoforms also showed distinct pharmacological profiles with differential sensitivity to block by zinc. Zinc was a potent blocker of alpha 1 beta 1 delta GABAR channels, a moderate-strength blocker of alpha 1 beta 1 gamma 2L delta GABAR channels, and did not block the alpha 1 beta 1 gamma 2L GABAR channels. These findings suggest that GABAR isoforms containing the delta subunit constitute a novel GABAR channel with distinct electrophysiological and pharmacological characteristics.
由大鼠α1、β1、γ2L和δ亚基的不同组合构成的GABAA受体通道（GABARs）在小鼠成纤维细胞（L929细胞）中瞬时表达。从转染细胞中获得全细胞记录，以确定GABAR亚基的哪些组合形成了功能性受体通道，并比较在有和没有δ亚基存在的情况下所表达的GABAR通道的电生理和药理学特性。只有α1β1γ2L、α1β1γ2Lδ和α1β1δ亚基组合组装形成功能性GABAR通道，并且δ亚基的存在减缓了GABA应用期间GABA诱发电流的急性脱敏速率以及GABA应用后GABA诱发电流的恢复速率。这三种不同的GABAR通道亚型也表现出不同的药理学特征，对锌阻断具有不同的敏感性。锌是α1β1δ GABAR通道的有效阻断剂，是α1β1γ2Lδ GABAR通道的中等强度阻断剂，并且不阻断α1β1γ2L GABAR通道。这些发现表明，含有δ亚基的GABAR亚型构成了一种具有独特电生理和药理学特征的新型GABAR通道。
