| Autor: |
Antflick, Jordan E., Hampson, David R. |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; Feb2012, Vol. 120 Issue 4, p552-563, 12p, 1 Black and White Photograph, 1 Diagram, 4 Graphs |
| Abstrakt: |
J. Neurochem. (2012) 120, 552-563. Abstract The regulation of pre-synaptic glutamate release is important in the maintenance and fidelity of excitatory transmission in the nervous system. In this study, we report a novel interaction between a ligand-gated ion channel and a G-protein coupled receptor which regulates glutamate release from parallel fiber axon terminals. Immunocytochemical analysis revealed that GABAA receptors and the high affinity group III metabotropic glutamate receptor subtype 4 (mGlu4) are co-localized on glutamatergic parallel fiber axon terminals in the cerebellum. GABAA and mGlu4 receptors were also found to co-immunoprecipitate from cerebellar membranes. Independently, these two receptors have opposing roles on glutamate release: pre-synaptic GABAA receptors promote, while mGlu4 receptors inhibit, glutamate release. However, coincident activation of GABAA receptors with muscimol and mGlu4 with the agonist (2 S)- S-2-amino-4-phosphonobutanoic acid , increased glutamate release from [3H]glutamate-loaded cerebellar synaptosomes above that observed with muscimol alone. Further support for an interaction between GABAA and mGlu4 receptors was obtained in the mGlu4 knockout mouse which displayed reduced binding of the GABAA ligand [35S] tert-butylbicyclophosphorothionate, and decreased expression of the α1, α6, β2 GABAA receptor subunits in the cerebellum. Taken together, our data suggest a new role for mGlu4 whereby simultaneous activation with GABAA receptors acts to amplify glutamate release at parallel fiber-Purkinje cell synapses. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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