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The synaptic activation of kainate receptors

Abstract

L-Glutamate, the principal excitatory neurotransmitter in the vertebrate central nervous system, acts on three classes of ionotropic glutamate receptors, named after the agonists AMPA, NMDA and kainate1. AMPA receptors are known to mediate fast synaptic responses and NMDA receptors to mediate slow synaptic responses at most excitatory synapses in the brain2. Kainate receptors are formed from a separate set of genes (GluR5–7, KA-1 and KA-2) and are widely distributed throughout the brain3,4,5,6,7,8. They are implicated in epileptogenesis and cell death9. However, the physiological functions of kainate receptors are not known7. The development of 2,3-benzodiazepine antagonists that are selective for AMPA receptors10 enables kainate receptors to be specifically activated by exogenous ligands, such as kainate11,12,13,14,15,16. Here we demonstrate that high-frequency stimulation of mossy fibres in rat hippocampal slices, in the presence of the highly selective AMPA receptor antagonist GYKI 53655 (1315,) plus NMDA- and GABA-receptor antagonists, activates an inward current in CA3 neurons that has a pharmacology typical of kainate receptors. The finding that kainate receptors can be activated synaptically adds to the diversity of information transfer at glutamatergic synapses.

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Figure 1: Synaptic activation of a non-AMPA, non-NMDA receptor-mediated EPSC by stimulation of mossy fibres.
Figure 2: Properties of the mossy fibre-evoked EPSC.
Figure 3: The mossy fibre EPSC is antagonized by CNQX.
Figure 4: Cyclothiazide potentiates the mossy fibre-evoked EPSC in the absence, but not in the presence, of the antagonist cocktail.

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Acknowledgements

We thank Eli Lilly for the GYKI 53655; W. W. Anderson for the on-line data acquisition and analysis programme, and J. C. Watkins for gifts of other compounds. This work was supported by the MRC and the European Community.

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Correspondence to Graham L. Collingridge.

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Vignes, M., Collingridge, G. The synaptic activation of kainate receptors. Nature 388, 179–182 (1997). https://doi.org/10.1038/40639

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