Presynaptic group I metabotropic glutamate receptors modulate synaptic transmission in the rat superior colliculus via 4-AP sensitive K(+) channels

A. M. White, R. A. Kylanpaa, L. A. Christie, S. J. McIntosh, A. J. Irving, Bettina Platt

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20 Citations (Scopus)

Abstract

1 Group I metabotropic glutamate receptors (mGluRs) are thought to be important modulators of neuronal function in the superior colliculus (SC). Here, we investigated the pharmacology and signalling mechanisms underlying group I mGluR-mediated inhibition of neuronal excitability and synaptic transmission in the rat SC slice.

2 The group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) potently depressed synaptically evoked excitatory postsynaptic potentials (EPSPs), currents (EPSCs), and action potentials in a dose-dependent manner (IC50: 6.3 muM). This was strongly reduced by the broad-spectrum antagonist (+)alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM, similar to95% reduction), by the mGluR1 antagonist LY367385 (100 muM, similar to 80% reduction) but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP, 1 - 100 muM).

3 The putative mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 muM) also inhibited EPSPs. Interestingly, CHPG's actions were not blocked by MPEP, but LY367385 (100 muM) reduced the effect of CHPG by 50%.

4 Inhibition induced by DHPG was independent of phospholipase C (PLC)/protein kinase C pathways, and did not require intact intracellular Ca2+ stores. It was not abolished but enhanced by the GABA(A) antagonist bicuculline (5 muM), suggesting that DHPG's action was not due to facilitated inhibition or changes in neuronal network activity.

5 The K+ channel antagonist 4-aminopyridine (4-AP, 50- 100 muM) converted the inhibitory effect of DHPG into facilitation. Paired-pulse depression was strongly reduced by DHPG, an effect that was also prevented by 4-AP.

6 Our data indicate that group I agonists regulate transmitter release, presumably via an autoreceptor in the SC. This receptor may be involved in adaptation to repetitive stimulation via a non-PLC mediated pathway.

Original languageEnglish
Pages (from-to)1421-1433
Number of pages12
JournalBritish Journal of Pharmacology
Volume140
Issue number8
DOIs
Publication statusPublished - Dec 2003

Keywords

  • DHPG
  • CHPG
  • paired pulse depression
  • slice
  • presynaptic
  • autoreceptor
  • short-term plasticity
  • PYRAMIDAL NEURONS
  • EXCITATORY TRANSMISSION
  • SUPERFICIAL LAYERS
  • ARACHIDONIC-ACID
  • CALCIUM-CHANNELS
  • VISUAL RESPONSES
  • CA2+ STORES
  • CA1 REGION
  • HIPPOCAMPUS
  • ACTIVATION

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