Vicini S, Alho H, Costa E, Mienville J M, Santi M R, Vaccarino F M
Proc Natl Acad Sci U S A. 1986 Dec;83(23):9269-73. doi: 10.1073/pnas.83.23.9269.
Inhibitory gamma-aminobutyric acid-mediated synaptic currents were studied in dissociated primary cultures of neonatal rat cortex with the whole-cell patch-clamp technique. Immunocytochemical staining of the cultures showed the presence of a large number of glutamic acid decarboxylase-containing neurons, and electrical stimulation of randomly selected neurons produced in many cases chloride-mediated and bicuculline-sensitive inhibitory synaptic currents in postsynaptic cells. The amplitude and decay time of the inhibitory synaptic currents were increased by flunitrazepam and decreased by the beta-carboline derivative methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, two high-affinity ligands for the allosteric regulatory sites of gamma-aminobutyric acid receptors. The imidazobenzodiazepine Ro 15-1788, another high-affinity ligand of the gamma-aminobutyric acid receptor regulatory sites that has negligible intrinsic activity, blocked the action of flunitrazepam and beta-carboline. However, Ro 15-1788 also increased the decay rate of the inhibitory synaptic currents. This might suggest that an endogenous ligand for the benzodiazepine-beta-carboline binding site is operative in gamma-aminobutyric acid-mediated synaptic transmission.
采用全细胞膜片钳技术，在新生大鼠皮质的原代解离培养物中研究了抑制性γ-氨基丁酸介导的突触电流。对培养物进行免疫细胞化学染色显示存在大量含谷氨酸脱羧酶的神经元，对随机选择的神经元进行电刺激在许多情况下会在突触后细胞中产生氯离子介导的、荷包牡丹碱敏感的抑制性突触电流。γ-氨基丁酸受体变构调节位点的两种高亲和力配体氟硝西泮使抑制性突触电流的幅度和衰减时间增加，而β-咔啉衍生物6,7-二甲氧基-4-乙基-β-咔啉-3-羧酸甲酯则使其降低。γ-氨基丁酸受体调节位点的另一种高亲和力配体咪唑并苯二氮卓Ro 15-1788，其内在活性可忽略不计，它阻断了氟硝西泮和β-咔啉的作用。然而，Ro 15-1788也增加了抑制性突触电流的衰减速率。这可能表明苯二氮卓-β-咔啉结合位点的内源性配体在γ-氨基丁酸介导的突触传递中起作用。
