Roles and rules of kainate receptors in synaptic transmission

Kainate receptors are a class of ionotropic glutamate receptors with remarkable structural diversity. There are five different subunits, some of which are susceptible to alternative splicing and mRNA editing. Pharmacologically, they are difficult to distinguish from other glutamate receptors, such as the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) type, but important progress has been made in identifying several relatively selective agonists and antagonists.Kainate receptors have pre- and postsynaptic distributions. Postsynaptic kainate receptors contribute to synaptic transmission, and the slow time-course of their response endows synapses with longer integration times. Presynaptically, kainate receptors modulate transmitter release from excitatory and inhibitory synapses in different brain regions. The presynaptic mechanisms whereby kainate receptors modulate excitation and inhibition are quite complex and remain a matter of debate.Kainate receptors are also involved in synaptic plasticity during development and in the adult, but their mechanism of action remains to be elucidated. Similarly, the long-held view that kainate receptors are relevant to the generation of epilepsy is a matter of debate, as there is contradictory evidence on their role as pro- or anticonvulsant molecules.In addition to these debates in the field, two additional observations make kainate receptors one of the most intriguing receptor family in the nervous system. First, although there are several kainate receptor-knockout animals, they have not been particularly informative about the function of these receptors. Second, some actions of kainate seem to involve the unusual interaction of an ionotropic receptor with a G protein.