Metabotropic actions of kainate receptors in the CNS

Kainate receptors (KARs), together with NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA), are typically described as ionotropic glutamate receptors. Although ionotropic functions for KARs are beginning to be characterized in multiple brain regions, both, in the pre- and post-synaptic compartments of the synapse, there is accumulating evidence that KARs mediate some of their effects without invoking ion-fluxes. Thus, since 1998, when the first metabotropic action of KARs was described in the modulation of GABA release in hippocampal interneurons, there have been increasing reports that some of the functions of KARs involve the participation of intracellular signalling cascades and depend on G protein activation. These surprising observations, attesting metabotropic actions of KARs, akin to those usually attributed to seven transmembrane region G protein-coupled receptors, make the physiological classification and description of glutamate receptors more complex. In the present review, we describe the metabotropic roles of KARs in the CNS and discuss the intriguing properties of this receptor which, structurally shows all the facets of a typical ionotropic receptor, but appears to express a metabotropic remit at some key synapses.