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Activation of ?-aminobutyric acid GAT-1 transporters on glutamatergic terminals of mouse spinal cord mediates glutamate release through anion channels and by transporter reversal
- Source :
- Journal of Neuroscience Research. 80:424-433
- Publication Year :
- 2005
- Publisher :
- Wiley, 2005.
-
Abstract
- The effects of gamma-aminobutyric acid (GABA) on the release of glutamate from mouse spinal cord nerve endings have been studied using superfused synaptosomes. GABA elicited a concentration-dependent release of [3H]D-aspartate ([3H]D-ASP; EC50= 3.76 microM). Neither muscimol nor (-)baclofen mimicked GABA, excluding receptor involvement. The GABA-evoked release was strictly Na+ dependent and was prevented by the GABA transporter inhibitor SKF89976A, suggesting involvement of GAT-1 transporters located on glutamatergic nerve terminals. GABA also potentiated the spontaneous release of endogenous glutamate; an effect sensitive to SKF89976A and low-Na+-containing medium. Confocal microscopy shows that the GABA transporter GAT-1 is coexpressed with the vesicular glutamate transporter vGLUT-1 and with the plasma membrane glutamate transporter EAAT2 in a substantial portion of synaptosomal particles. The GABA effect was external Ca2+ independent and was not decreased when cytosolic Ca2+ ions were chelated by BAPTA. The glutamate transporter blocker DL-TBOA or dihydrokainate inhibited in part (approximately 35%) the GABA (10 microM)-evoked [3H]D-ASP release; this release was strongly reduced by the anion channel blockers niflumic acid and NPPB. GABA, up to 30 microM, was unable to augment significantly the basal release of [3H]glycine from spinal cord synaptosomes, indicating selectivity for glutamatergic transmission. It is concluded that GABA GAT-1 transporters and glutamate transporters coexist on the same spinal cord glutamatergic terminals. Activation of these GABA transporters elicits release of glutamate partially by reversal of glutamate transporters present on glutamatergic terminals and largely through anion channels.
- Subjects :
- Anions
GABA Plasma Membrane Transport Proteins
Glutamate decarboxylase
Glycine
Presynaptic Terminals
Glutamic Acid
Synaptic Transmission
Ion Channels
Mice
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Glutamatergic
BAPTA
medicine
Animals
GABA transporter
Enzyme Inhibitors
GABA Agonists
gamma-Aminobutyric Acid
Transporter reversal
Dose-Response Relationship, Drug
biology
Niflumic acid
Glutamate receptor
Membrane Transport Proteins
Niflumic Acid
Excitatory Amino Acid Transporter 2
Spinal Cord
nervous system
chemistry
Muscimol
Biochemistry
Nitrobenzoates
Vesicular Glutamate Transport Protein 1
biology.protein
Biophysics
Calcium
Female
Synaptosomes
medicine.drug
Subjects
Details
- ISSN :
- 10974547 and 03604012
- Volume :
- 80
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience Research
- Accession number :
- edsair.doi.dedup.....f5e4a1f624aa4cbab0be555042f9459e