Kleingoor C, Wieland H A, Korpi E R, Seeburg P H, Kettenmann H
Department of Neurobiology, University of Heidelberg, Germany.
Neuroreport. 1993 Feb;4(2):187-90. doi: 10.1097/00001756-199302000-00018.
The GABAA/benzodiazepine receptor is the principal inhibitory neurotransmitter receptor in the mammalian brain and is assembled from sequence-related subunits, such as alpha 1 beta 2 gamma 2. In contrast to alpha 1 beta 2 gamma 2 receptors, alpha 6 beta 2 gamma 2 receptors fail to exhibit high-affinity binding of allosteric positive modulators of GABA-activated chloride currents. The critical determinant responsible for this difference in ligand binding was previously traced to a position in the extracellular domain of the two alpha subunits (alpha 1 His100 and alpha 6 Arg 101). We now show by patch clamp analysis that this amino acid exchange also determines the diazepam potentiation. Thus, alpha 1(Arg101)beta 2 gamma 2 receptors do not, but alpha 6(His100)beta 2 gamma 2 receptors do exhibit diazepam potentiation. However, the same extracellular determinant is not responsible for the increased GABA sensitivity of alpha 6 beta 2 gamma 2 receptors relative to alpha 1 beta 2 gamma 2 receptors as revealed by electrophysiological analysis and by differential GABA sensitivity of [35S]TBPS binding.
GABAA/苯二氮䓬受体是哺乳动物大脑中主要的抑制性神经递质受体，由序列相关的亚基组装而成，如α1β2γ2。与α1β2γ2受体不同，α6β2γ2受体未能表现出对GABA激活的氯离子电流变构正性调节剂的高亲和力结合。先前将负责这种配体结合差异的关键决定因素追溯到两个α亚基（α1的His100和α6的Arg 101）细胞外结构域中的一个位置。我们现在通过膜片钳分析表明，这种氨基酸交换也决定了地西泮的增强作用。因此，α1(Arg101)β2γ2受体不表现，但α6(His100)β2γ2受体确实表现出地西泮增强作用。然而，如电生理分析和[35S]TBPS结合的不同GABA敏感性所揭示的，相同的细胞外决定因素并不导致α6β2γ2受体相对于α1β2γ2受体GABA敏感性增加的原因。
