Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.
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Authors
Ghirardini, Elsa
Wadle, Simon L
Augustin, Vanessa
Becker, Jasmin
Brill, Sina
Hammerich, Julia
Seifert, Gerald
Publication Date
2018-01-25Journal Title
Mol Brain
ISSN
1756-6606
Publisher
Springer Science and Business Media LLC
Volume
11
Issue
1
Pages
4
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Ghirardini, E., Wadle, S. L., Augustin, V., Becker, J., Brill, S., Hammerich, J., Seifert, G., & et al. (2018). Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.. Mol Brain, 11 (1), 4. https://doi.org/10.1186/s13041-018-0346-y
Abstract
Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC) neurons receive glycinergic and GABAergic inputs, whereas inhibition in hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express neurotransmitter transporters and are expected to adapt to the local requirements regarding neurotransmitter homeostasis. Here we analyzed the expression of inhibitory neurotransmitter transporters in IC and HC astrocytes using whole-cell patch-clamp and single-cell reverse transcription-PCR. We show that most astrocytes in both regions expressed functional glycine transporters (GlyTs). Activation of these transporters resulted in an inward current (IGly) that was sensitive to the competitive GlyT1 agonist sarcosine. Astrocytes exhibited transcripts for GlyT1 but not for GlyT2. Glycine did not alter the membrane resistance (RM) arguing for the absence of functional glycine receptors (GlyRs). Thus, IGly was mainly mediated by GlyT1. Similarly, we found expression of functional GABA transporters (GATs) in all IC astrocytes and about half of the HC astrocytes. These transporters mediated an inward current (IGABA) that was sensitive to the competitive GAT-1 and GAT-3 antagonists NO711 and SNAP5114, respectively. Accordingly, transcripts for GAT-1 and GAT-3 were found but not for GAT-2 and BGT-1. Only in hippocampal astrocytes, GABA transiently reduced RM demonstrating the presence of GABAA receptors (GABAARs). However, IGABA was mainly not contaminated by GABAAR-mediated currents as RM changes vanished shortly after GABA application. In both regions, IGABA was stronger than IGly. Furthermore, in HC the IGABA/IGly ratio was larger compared to IC. Taken together, our results demonstrate that astrocytes are heterogeneous across and within distinct brain areas. Furthermore, we could show that the capacity for glycine and GABA uptake varies between both brain regions.
Keywords
Hippocampus, Astrocytes, Animals, Mice, Inbred C57BL, gamma-Aminobutyric Acid, Glycine, Ion Channel Gating, Kinetics, GABA Plasma Membrane Transport Proteins, Glycine Plasma Membrane Transport Proteins, Inferior Colliculi, Single-Cell Analysis
Identifiers
External DOI: https://doi.org/10.1186/s13041-018-0346-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277465
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