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 Gi/o protein thought to couple via its Gβγ subunit to a decrease in Ca2+ 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 Ca2+-dependent (rather than GPCR-dependent) activation of adenylate cyclase (AC). At high KA concentrations (<100 nM), a mechanism involving a pertussis toxin-sensitive Gi/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.
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Rodríguez-Moreno, A., Sihra, T.S. (2011). Metabotropic Actions of Kainate Receptors in the Control of Glutamate Release in the Hippocampus. In: Rodríguez-Moreno, A., Sihra, T.S. (eds) Kainate Receptors. Advances in Experimental Medicine and Biology, vol 717. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9557-5_4
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