Presynaptic group I metabotropic glutamate receptors modulate synaptic transmission in the rat superior colliculus via 4-AP sensitive K(+) channels.
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.
White
Anne-Marie
AM
Department of Biomedical Sciences, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, Scotland.
Kylänpää
Risto A
RA
Christie
Louisa A
LA
McIntosh
Simon J
SJ
Irving
Andrew J
AJ
Platt
Bettina
B
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012118:Resorcinols / Q000008:administration & dosage / Q000494:pharmacology; D013477:Superior Colliculi / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D026902:Potassium Channel Blockers; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine; D015761:4-Aminopyridine; D005998:Glycine