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

Br J Pharmacol. 2003 Dec;140(8):1421-33. doi: 10.1038/sj.bjp.0705570. Epub 2003 Nov 17.


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 microm). This was strongly reduced by the broad-spectrum antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mm, approximately 95% reduction), by the mGluR1 antagonist LY367385 (100 microm, approximately 80% reduction) but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 1-100 microm). 3. The putative mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 microm) also inhibited EPSPs. Interestingly, CHPG's actions were not blocked by MPEP, but LY367385 (100 microm) 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 GABAA antagonist bicuculline (5 microm), 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 microm) 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.

Publication types

  • Comparative Study

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Glycine / administration & dosage
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • In Vitro Techniques
  • Ion Channel Gating
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Receptors, Presynaptic / agonists
  • Receptors, Presynaptic / antagonists & inhibitors
  • Receptors, Presynaptic / physiology*
  • Resorcinols / administration & dosage
  • Resorcinols / pharmacology
  • Superior Colliculi / metabolism
  • Superior Colliculi / physiology*
  • Synaptic Transmission / physiology*


  • Calcium Channel Blockers
  • Excitatory Amino Acid Agonists
  • Potassium Channel Blockers
  • Receptors, Metabotropic Glutamate
  • Receptors, Presynaptic
  • Resorcinols
  • metabotropic glutamate receptor type 1
  • 3,5-dihydroxyphenylglycine
  • 4-Aminopyridine
  • Glycine