Metabotropic actions of kainate receptors in the control of GABA release.

Kainate receptors (KARs) are members of the family of ionotropic glutamate receptors (iGluRs) which also include NMDA and AMPA receptors. As ionotropic receptors, KARs have been characterized, pre and postsynaptically, in several brain regions. In this chapter we review evidence that suggests that KARs mediate some of their effects without invoking ion-fluxes. Beginning with seminal experiments described some ten years ago, when the notion of a metabotropic action of KAR was first posited in the modulation of GABA release from hippocampal interneurons, increasingly, there have been reports indicating that some KAR functions overtly depend on G-protein activation and involve the participation of intracellular signalling cascades. Thus, KAR activation instigates a cascade involving G(i/o), phospholipase C and protein kinase C to suppress the release of GABA and therefore underpins disinhibition of pyramidal cells in the CA1 region of the hippocampus. This type of metabotropic function of KARs in controlling GABA release represents an additional level of activity-dependent control of synaptic inhibition which is independent of any ionotropic activity of KARs.