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首页> 外文期刊>The European Journal of Neuroscience >Differential localization and function of GABA transporters, GAT-1 and GAT-3, in the rat globus pallidus.
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Differential localization and function of GABA transporters, GAT-1 and GAT-3, in the rat globus pallidus.

机译:大鼠苍白球中GABA转运蛋白GAT-1和GAT-3的差异化定位和功能。

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摘要

GABA transporter subtype 1 (GAT-1) and GABA transporter subtype 3 (GAT-3) are the main transporters that regulate inhibitory GABAergic transmission in the mammalian brain through GABA reuptake. In this study, we characterized the ultrastructural localizations and determined the respective roles of these transporters in regulating evoked inhibitory postsynaptic currents (eIPSCs) in globus pallidus (GP) neurons after striatal stimulation. In the young and adult rat GP, GAT-1 was preferentially expressed in unmyelinated axons, whereas GAT-3 was almost exclusively found in glial processes. Except for rare instances of GAT-1 localization, neither of the two transporters was significantly expressed in GABAergic terminals in the rat GP. 1-(4,4-Diphenyl-3-butenyl)-3-piperidinecarboxylic acid hydrochloride (SKF 89976A) (10 mum), a GAT-1 inhibitor, significantly prolonged the decay time, but did not affect the amplitude, of eIPSCs induced by striatal stimulation (15-20 V). On the other hand, the semi-selective GAT-3 inhibitor 1-(2-[tris(4-methoxyphenyl)methoxy]ethyl)-(S)-3-piperidinecarboxylic acid (SNAP 5114) (10 mum) increased the amplitude and prolonged the decay time of eIPSCs. The effects of transporter blockade on the decay time and amplitude of eIPSCs were further increased when both inhibitors were applied together. Furthermore, SKF 89976A or SNAP 5114 blockade also increased the amplitude and frequency of spontaneous IPSCs, but did not affect miniature IPSCs. Significant GABA(A) receptor-mediated tonic currents were induced in the presence of high concentrations of both SKF 89976A (30 mum) and SNAP 5114 (30 mum). In conclusion, these data indicate that GAT-1 and GAT-3 represent different target sites through which GABA reuptake may subserve complementary regulation of GABAergic transmission in the rat GP.
机译:GABA转运蛋白亚型1(GAT-1)和GABA转运蛋白亚型3(GAT-3)是通过GABA重摄取调节哺乳动物脑中抑制性GABA能传递的主要转运蛋白。在这项研究中,我们表征了超微结构定位,并确定了这些转运蛋白在调节纹状体刺激后苍白球(GP)神经元诱发的抑制性突触后突触电流(eIPSCs)中的各自作用。在年轻和成年大鼠GP中,GAT-1在未髓鞘的轴突中优先表达,而GAT-3几乎仅在神经胶质突中发现。除了极少的GAT-1定位,两种转运蛋白均未在大鼠GP的GABA能端中显着表达。 GAT-1抑制剂1-(4,4-二苯基-3-丁烯基)-3-哌啶羧酸盐酸盐(SKF 89976A)(10毫米)可显着延长诱导eIPSC的衰减时间,但不影响振幅通过纹状体刺激(15-20 V)。另一方面,半选择性GAT-3抑制剂1-(2- [三[4-(4-甲氧基苯基)甲氧基]乙基]-(S)-3-哌啶甲酸(SNAP 5114)(10毫米)增加了振幅,延长了eIPSC的衰减时间。当两种抑制剂一起使用时,转运蛋白封锁对eIPSC的衰减时间和幅度的影响进一步增加。此外,SKF 89976A或SNAP 5114封锁还增加了自发IPSC的幅度和频率,但不影响微型IPSC。在高浓度的SKF 89976A(30毫米)和SNAP 5114(30毫米)同时存在的情况下,诱导出明显的GABA(A)受体介导的强直电流。总之,这些数据表明,GAT-1和GAT-3代表了不同的靶位点,GABA的再摄取可以通过这些靶位服从大鼠GP中GABA能传递的互补调节。

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