METABOTROPIC GLUTAMATE RECEPTOR-MEDIATED EXCITATION AND INHIBITION OFSYMPATHETIC PREGANGLIONIC NEURONS

The effects of metabotropic glutamate receptor (mGluR) subtype selecti ve compounds on the excitability of sympathetic preganglionic neurones (SPNs) were investigated. Non-selective mGluR agonists (1S,3R)-aminoc yclopentane-1,3-dicarboxylic acid and (2S, 1'S, 2'S)-2-(carboxycyclopr opyl)glycine, induced dose-dependent depolarisations in 96 and 75% of SPNs, respectively and hyperpolarisations in 2 and 21% of SPNs. Both a gonists could induce subthreshold membrane potential oscillations in p reviously non-oscillating SPNs and either increased or reduced the fre quency of spontaneously occurring oscillations. A selective group I mG luR agonist, 3,5-dihydroxyphenylglycine, depolarised all SPNs tested, induced oscillations in membrane potential of otherwise non-oscillatin g SPNs and increased the frequency of spontaneous oscillations. Agonis ts with selectivity for group II mGluRs (1S, 3S)-aminocyclopentane-1,3 -dicarboxylic acid and (S)-4-carboxy-3-hydroxy-phenylglycine ((S)-4C3H PG) did not induce depolarising responses. However (S)-4C3HPG induced hyperpolarising responses associated with a reduction in the frequency of spontaneous oscillations in two of six SPNs tested. Depolarising a nd hyperpolarising responses were maintained in the presence of tetrod otoxin indicating a direct action of the agonists upon SPNs. In indivi dual SPNs responses of opposite polarity could be induced from the sam e initial membrane potential using different agonists, indicating that the opposing responses involved different ionic mechanisms. The broad spectrum mGluR antagonist (S)-alpha-methyl-4-carboxyphenylglycine and the selective group I mGluR antagonist (S)-4-carboxyphenylglycine rev ersibly depressed mGluR agonist induced depolarisations. These results indicate that SPNs express two mGluR populations with opposing action s on neuronal excitability: group I mGluRs depolarise SPNs and can dri ve oscillatory membrane potential activity; a minority of SPNs express group II mGluRs which mediate membrane hyperpolarisations and reduce the frequency of membrane potential oscillations. (C) 1998 Elsevier Sc ience Ltd. All rights reserved.