title: Metabotropic actions of kainate receptors in the control of glutamate release in the hippocampus.
abstract: Kainate-type glutamate receptors (KARs) structurally present the credentials of the other ionotropic glutamate receptor (iGluR) family members (NMDA and AMPA receptors), but functionally often purport examples of a metabotropic mode of operation. In the present chapter, we describe these metabotropic roles of KARs in the modulation of glutamate release in the hippocampus at CA3 Schaffer Collateral (SC)-CA1 Pyramidal Cell (PC) synapses and dentate gyrus granule cell Mossy Fiber (MF)-CA3 PC synapses. As autoreceptors on SC terminals, KARs inhibit the release of glutamate at SC-CA1 PC synapses through a mechanism dependent on a pertussis toxin-sensitive G(i/o) protein thought to couple via its Gβγ subunit to a decrease in Ca(2+) channel function. At MF-CA3 PC synapses, autoreceptors on MF terminals respond diametrically depending on the agonist concentration. At low KA concentrations (< 100 nM), a G-protein-independent process invokes the activation of proteins kinase A (PKA) to effect a facilitation of glutamate release. This facilitation possibly involves the Ca(2+)-dependent (rather than GPCR-dependent) activation of adenylate cyclase (AC). At high KA concentrations (<100 nM), a mechanism involving a pertussis toxin-sensitive G(i/o) protein is invoked to inhibit AC activity and thereby suppress PKA activity. Taken together with the heterosynaptic regulation of GABA release by KARs working with a metabotropic modus operandi, there is therefore compelling evidence that these ionotropic glutamate receptors are involved in a noncanonical modulation of glutamate release that does not rely on their typical ionotropic activity.
authors.affiliation: Departamento de Fisiología, Anatomía y Biologfa Celular, Universidad Pablo de Olavide, Ctra. de Utrera, Km. 1, 41013, Sevilla, Spain. arodmor@upo.es
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Moreno
authors.forename: Talvinder S
authors.initials: TS
authors.lastname: Sihra
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D018092:Kainic Acid Receptors / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D018092:Kainic Acid Receptors