Lie Maria E K, Al-Khawaja Anas, Damgaard Maria, Haugaard Anne S, Schousboe Arne, Clarkson Andrew N, Wellendorph Petrine
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Department of Anatomy, Brain Health Research Centre and Brain Research New Zealand, University of Otago, 9054, Dunedin, New Zealand.
Adv Neurobiol. 2017;16:137-167. doi: 10.1007/978-3-319-55769-4_7.
Imbalances in GABA-mediated tonic inhibition are involved in several pathophysiological conditions. A classical way of controlling tonic inhibition is through pharmacological intervention with extrasynaptic GABA receptors that sense ambient GABA and mediate a persistent GABAergic conductance. An increase in tonic inhibition may, however, also be obtained indirectly by inhibiting glial GABA transporters (GATs). These are sodium-coupled membrane transport proteins that normally act to terminate GABA neurotransmitter action by taking up GABA into surrounding astrocytes. The aim of the review is to provide an overview of glial GATs in regulating tonic inhibition, especially in epilepsy and stroke. This entails a comprehensive summary of changes known to occur in GAT expression levels and signalling following epileptic and ischemic insults. Further, we discuss the accumulating pharmacological evidence for targeting GATs in these diseases.
γ-氨基丁酸（GABA）介导的紧张性抑制失衡与多种病理生理状况有关。控制紧张性抑制的经典方法是通过对突触外GABA受体进行药理学干预，这些受体可感知周围环境中的GABA并介导持续性GABA能电流。然而，增强紧张性抑制也可通过抑制胶质细胞GABA转运体（GATs）间接实现。GATs是钠耦联膜转运蛋白，通常通过将GABA摄取到周围星形胶质细胞中来终止GABA神经递质的作用。本综述的目的是概述胶质细胞GATs在调节紧张性抑制中的作用，尤其是在癫痫和中风方面。这需要全面总结癫痫和缺血性损伤后GAT表达水平和信号传导已知发生的变化。此外，我们还讨论了在这些疾病中靶向GATs的越来越多的药理学证据。
