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Review
. 2017:16:137-167.
doi: 10.1007/978-3-319-55769-4_7.

Glial GABA Transporters as Modulators of Inhibitory Signalling in Epilepsy and Stroke

Maria E K Lie  1 , Anas Al-Khawaja  1 , Maria Damgaard  1 , Anne S Haugaard  1 , Arne Schousboe  1 , Andrew N Clarkson  2   3 , Petrine Wellendorph  4
Affiliations
Review

Glial GABA Transporters as Modulators of Inhibitory Signalling in Epilepsy and Stroke

Maria E K Lie et al. Adv Neurobiol. 2017.

Abstract

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 GABAA 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.

Keywords: BGT1; Epilepsy; GABAA receptors; GAT; GAT1; GAT3; Ischemic stroke; Tonic inhibition.

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