GAT-3 transporters regulate inhibition in the neocortex
GAT-3 transporters regulate inhibition in the neocortex
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DOI：
10.1152/jn.00420.2005
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发表时间：
2005-12-01
影响因子：
2.5
通讯作者：
Kinney, GA
中科院分区：
文献类型：
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作者：
Kinney, GA
作者：Gregory A. GAT-3转运蛋白调节新皮层中的抑制。神经生理学杂志94：4533- 4537，2005.首次发表于2005年8月31日;doi：10.1152/jn.00420.2005。GAT-3转运蛋白在调节GABA A受体介导的抑制中的作用在大鼠新皮层中使用体外切片制备进行了检查。药理学分离的GABA A受体介导的反应记录从第V层新皮质锥体细胞，SNAP-5114，GAT- 3 GABA转运选择性拮抗剂的影响进行了评价。SNAP-5114的应用导致在大多数细胞中的诱发GABA A反应的幅度可逆增加，虽然没有观察到对衰减时间的影响。抑制性中间神经元的自发输出的检查揭示了作为GAT-3抑制的结果的自发抑制性突触电流的频率和幅度的可逆增加。GAT-3抑制对自发抑制事件的这种作用是动作电位依赖性的，因为在TTX存在下应用SNAP-5114时未观察到这种增加。这些结果表明，GAT-3转运蛋白调节新皮层中的抑制性中间神经元输出。由应用SNAP-5114引起的抑制性中间神经元兴奋性的增加表明GAT-3转运蛋白功能的抑制导致周围GABA水平的降低，这可能是通过减少经由GAT-3转运蛋白的载体介导的GABA释放。
Kinney, Gregory A. GAT-3 Transporters regulate inhibition in the neocortex. J Neurophysiol 94:4533-4537,2005. First published August 31,2005;doi:10.1152/jn.00420.2005. The role of GAT-3 transporters in regulating GABA A receptor-mediated inhibition was examined in the rat neocortex using an in vitro slice preparation. Pharmacologically isolated GABA A receptor-mediated responses were recorded from layer V neocortical pyramidal cells, and the effects of SNAP-5114, a GAT- 3 GABA transporter-selective antagonist, were evaluated. Application of SNAP-5114 resulted in a reversible increase in the amplitude of an evoked GABA A response in most cells examined, although no effect on the decay time was observed. Examination of the spontaneous output of inhibitory interneurons revealed a reversible increase in the frequency and amplitude of spontaneous inhibitory synaptic currents as a consequence of GAT-3 inhibition. This effect of GAT-3 inhibition on spontaneous inhibitory events was action potential-dependent because no such increases were observed when SNAP-5114 was applied in the presence of TTX. These results demonstrate that GAT-3 transporters regulate inhibitory interneuron output in the neocortex. The increase in inhibitory interneuron excitability resulting from application of SNAP-5114 suggests that inhibition of GAT-3 transporter function results in a reduction in ambient GABA levels, possibly by a reduction in carrier-mediated GABA release via the GAT-3 transporter.