Glutamate receptors of the kainate type and synaptic transmission

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Glutamic acid is an important excitatory neurotransmitter in the mammalian CNS. It has been established that synaptic transmission is mediated mostly by the ionotropic glutamate receptors AMPA and NMDA, with fast and slow kinetics, respectively. The recent demonstration in hippocampal neurones of a class of glutamate receptors that are activated by kainate and not by AMPA (that is, kainate-selective receptors) opens the possibility that receptors, others than those of the AMPA type, might also be involved in fast neurotransmission. The lack of specific pharmacological tools to dissect out AMPA from kainate receptors has hampered the functional study of kainate receptors. However, the recent finding that a 2,3-benzodiazepine (GYKI53655) behaves as a selective antagonist of AMPA receptors allows us to address the question of the role of rapidly inactivating kainate receptors in synaptic transmission.

Section snippets

Fast synaptic responses lack a kainate receptor-mediated component

The fast synaptic component of monosynaptically elicited responses from either single microislands containing two neurones or two connected singleneurone microislands (see Fig. 3A), showed close similarity to the well-known AMPA receptor-mediated component of synaptic transmission. Many instances exist in the literature where a complete block of synaptic transmission was found upon AMPA-receptor blockage (for example, see 22,Refs 22,23). However, these results were obtained with non-selective

A glutamate receptor in search of a role

It is clear from the experiments described above that kainate receptors do not participate in conventional synaptic transmission in cultured cells, nor in adult neuronal populations. Thus, the question remains as to what is the role of kainate receptors? At present, we lack the additional pharmacological tools to approach this question. It has been described, however, that kainate produces a decrease in [3H]glutamate release from hippocampal synaptosomes31. The same group showed a reduction of

Concluding remarks

It is now well established that hippocampal neurones express glutamate receptors that are selectively activated by kainate. Kainate-elicited responses undergo rapid and total desensitization, the recovery from which is rather slow, and AMPA, even at high concentrations, does not activate these receptors. Kainate receptors sharing many of the properties described in neurones have been found in O–2A progenitor cells and astrocytes. Moreover, glutamate receptors with a higher affinity for kainate

Acknowledgements

This article is dedicated to the memory of Elvira Garrido; her love, encouragement and happiness remain in our hearts. We thank D. Leander (Elli Lilly & Co, Indianapolis, IN, USA) for the generous gift of GYKI53655; A. Gutiérrez for preparing microcultures; D. Guinea for excellent technical help and C. Bailón for confocal microscopy facilities. English corrections by M. Sefton were appreciated. JL acknowledges grants from the DGICYT (PB93/0150), FIS (95/0869) and the Biotech Program of the

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