RIKEN Brain Science Institute Wako-shi, Saitama, Japan.
Front Cell Neurosci. 2013 Mar 13;7:23. doi: 10.3389/fncel.2013.00023. eCollection 2013.
Tonic GABA type A (GABAA) conductance is a key factor regulating neuronal excitability and computation in neuronal networks. The magnitude of the tonic GABAA conductance depends on the concentration of ambient GABA originating from vesicular and non-vesicular sources and is tightly regulated by GABA uptake. Here we show that the transport system regulating ambient GABA responsible for tonic GABAA conductances in hippocampal CA1 interneurons depends on its source. In mice, GABA from vesicular sources is regulated by mouse GABA transporter 1 (mGAT1), while that from non-vesicular sources by mouse GABA transporters 3/4 (mGAT3/4). This finding suggests that the two transporter systems do not just provide backup for each other, but regulate distinct signaling pathways. This allows individual tuning of the two signaling systems and indicates that drugs designed to act at specific transporters will have distinct therapeutic actions.
紧张型 GABA 型 A 受体（GABAA）电导率是调节神经元兴奋性和网络神经元计算的关键因素。紧张型 GABAA 电导率的大小取决于来自囊泡和非囊泡来源的周围 GABA 的浓度，并且受到 GABA 摄取的严格调节。在这里，我们表明，负责调节海马 CA1 中间神经元紧张型 GABAA 电导率的调节周围 GABA 的转运系统取决于其来源。在小鼠中，囊泡来源的 GABA 由小鼠 GABA 转运蛋白 1（mGAT1）调节，而非囊泡来源的 GABA 由小鼠 GABA 转运蛋白 3/4（mGAT3/4）调节。这一发现表明，这两个转运系统不仅仅是相互提供备份，而是调节不同的信号通路。这允许对两个信号系统进行单独调整，并表明旨在针对特定转运体发挥作用的药物将具有不同的治疗作用。
