Metabotropic glutamate receptor modulation of excitotoxicity in the neostriatum: role of calcium channels |
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Authors: | Christopher S. Colwell Michael S. Levine |
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Affiliation: | Mental Retardation Research Center, Department of Psychiatry and Biobehavioral Sciences, University of California-Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA. ccolwell@mednet.ucla.edu |
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Abstract: | We have previously shown that metabotropic glutamate receptor (mGluR) activation can attenuate N-methyl-d-aspartate (NMDA)-induced excitotoxic injury in the neostriatum both in vivo and in vitro. Our earlier studies made use of the non-subtype selective mGluR agonist 1-amino-cyclopentane-1,3-dicarboxylic acid (tACPD). In the present study, we extended these observations by identifying the subtype of mGluR involved. Using selective mGluR agonists, we provide evidence that the Group II mGluRs are responsible for inhibition of NMDA excitotoxicity in the neostriatum. In addition, we provide evidence that the inhibitory effects of tACPD on excitotoxicity are dependent upon calcium influx as they are blocked by a low calcium solution as well as the broad-spectrum calcium channel blocker cadmium. The tACPD-induced attenuation was also blocked by omega-conotoxin GVIA suggesting participation of N-type calcium channels. Whole cell voltage clamp recordings were made to directly determine the effects of mGluRs on voltage-gated calcium channels in neostriatal neurons. As predicted, both tACPD and the Group II agonist 3C4HPG inhibited calcium currents in neostriatal neurons. Again this effect was blocked by omega-conotoxin GVIA. Overall the results suggest that mGluR regulation of voltage-gated calcium channels can limit NMDA toxicity in the neostriatum. |
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Keywords: | Calcium channel Excitotoxity Metabotropic glutamate receptor Neostriatum N-Methyl- http://www.sciencedirect.com/cache/MiamiImageURL/B6SYR-3WWMN7J-D-C/0?wchp=dGLbVzz-zSkWW" alt=" Image" title=" Image" style=" vertical-align:bottom" border=" 0" height=11 width=" 16" />-aspartate Toxicity |
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