title: The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus.
abstract: Activation of kainate receptors depresses excitatory synaptic transmission in the hippocampus. In the present study, we have utilised a GluR5 selective agonist, ATPA [(RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid], and a GluR5 selective antagonist, LY294486 [(3SR,4aRS,6SR,8aRS)-6-([[(1H-tetrazol-5-y l)methyl]oxy]methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3 -carboxylic acid], to determine whether GluR5 subunits are involved in this effect. ATPA mimicked the presynaptic depressant effects of kainate in the CA1 region of the hippocampus. It depressed reversibly AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-mediated field excitatory postsynaptic potentials (field EPSPs) with an IC50 value of approximately 0.60 microM. The dual-component excitatory postsynaptic current (EPSC) and the pharmacologically isolated NMDA (N-methyl-D-aspartate) receptor-mediated EPSC were depressed to a similar extent by 2 microM ATPA (61 +/- 7% and 58 +/- 6%, respectively). Depressions were associated with an increase in the paired-pulse facilitation ratio suggesting a presynaptic locus of action. LY294486 (20 microM) blocked the effects of 2 microM ATPA on NMDA receptor-mediated EPSCs in a reversible manner. In area CA3, 1 microM ATPA depressed reversibly mossy fibre-evoked synaptic transmission (by 82 +/- 10%). The effects of ATPA were not accompanied by any changes in the passive properties of CA1 or CA3 neurones. However, in experiments where K+, rather than Cs+, containing electrodes were used, a small outward current was observed. These results show that GluR5 subunits comprise or contribute to a kainate receptor that regulates excitatory synaptic transmission in both the CA1 and CA3 regions of the hippocampus.
authors.affiliation: Department of Anatomy, University of Bristol, UK.
authors.forename: M
authors.initials: M
authors.lastname: Vignes
authors.forename: V R
authors.initials: VR
authors.lastname: Clarke
authors.forename: M J
authors.initials: MJ
authors.lastname: Parry
authors.forename: D
authors.initials: D
authors.lastname: Bleakman
authors.forename: D
authors.initials: D
authors.lastname: Lodge
authors.forename: P L
authors.initials: PL
authors.lastname: Ornstein
authors.forename: G L
authors.initials: GL
authors.lastname: Collingridge
mesh_terms: D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007555:Isoxazoles / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D007555:Isoxazoles; D011422:Propionates; D018092:Kainic Acid Receptors; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate