Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons

Abstract

Glutamate, the neurotransmitter at most excitatory synapses in the brain, activates a variety of receptor subtypes that can broadly be divided into ionotropic (ligand-gated ion channels) and metabotropic (G-protein-coupled) receptors. Ionotropic receptors mediate fast excitatory synaptic transmission, and based on pharmacological and molecular biological studies are divided into NMDA and non-NMDA subtypes. The non-NMDA receptor group is further divided into AMPA and kainate subtypes. Virtually all fast excitatory postsynaptic currents studied so far in the central nervous system are mediated by the AMPA and NMDA subtypes of receptors. Surprisingly, despite extensive analysis of their structure, biophysical properties and anatomical distribution, a synaptic role for kainate receptors in the brain has not been found. Here we report that repetitive activation of the hippocampal mossy fibre pathway, which is associated with high-affinity kainate binding and many of the kainate receptor subtypes, generates a slow excitatory synaptic current with all of the properties expected of a kainate receptor. This activity-dependent synaptic current greatly augments the excitatory drive of CA3 pyramidal cells.

KRIP6: A novel BTB/kelch protein regulating function of kainate receptors

“…Kainate receptors are widely expressed in the central nervous system (Wisden and Seeburg, 1993), where they can act pre-and post-synaptically. In the hippocampus, postsynaptic kainate receptors are thought to mediate excitatory transmission via an ionotropic action (Castillo et al, 1997;Cossart et al, 2002;Cossart et al, 1998) and to regulate excitability via a metabotropic function (Melyan et al, 2004;Melyan et al, 2002;Ruiz et al, 2005). Activation of presynaptic kainate receptors regulates glutamate and GABA release (Kullmann, 2001;Rodriguez-Moreno and Lerma, 1998) and modulates excitability in mature (Schmitz et al, 2000) and developing hippocampus.…”

“…Activation of presynaptic kainate receptors regulates glutamate and GABA release (Kullmann, 2001;Rodriguez-Moreno and Lerma, 1998) and modulates excitability in mature (Schmitz et al, 2000) and developing hippocampus. Kainate receptors mediate a component of synaptic transmission at mossy fiber to CA3 inputs (Castillo et al, 1997;Vignes and Collingridge, 1997) and are required for short-and long-term synaptic remodeling at hippocampal and cortical synapses (Bortolotto et al, 1999;Contractor et al, 2001;Park et al, 2006;Rodriguez-Moreno and Lerma, 1998). Kainate receptor activation contributes to developmental regulation of GABAergic transmission , to seizure generation (Ben-Ari and Cossart, 2000;Mulle et al, 1998) and epileptiform burst activity (Fisahn et al, 2004).…”

Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics

“…8 KA receptors have been reported to generate a slow excitatory activity-dependent synaptic current, which greatly augments excitatory currents of hippocampal CA3 pyramidal cells. 9 While located both pre-and postsynapticlly, KA receptors play significant roles in the regulation of hippocampal excitability. They inhibit glutamate release presynaptially [10][11][12] and also regulate action potential-dependent GABA release from interneurons.…”

Differential contribution of kainate receptors to excitatory postsynaptic currents in superficial layer neurons of the rat medial entorhinal cortex

“…Furthermore, the expression of postsynaptic KARs has been shown to be restricted in a cellular and subcellular manner. For instance, CA3 pyramidal neurons of the hippocampus have been shown to have postsynaptic KARs that mediate a substantial portion of the synaptic response, specifically at their mossy fiber synapse, while CA1 neurons do not have postsynaptic KAR mediated EPSCs (Castillo et al, 1997, Frerking et al, 1998, Bureau et al, 1999, Lerma et al, 2001. Additionally, KARs in hippocampal CA3 neurons have been shown to underlie the kainate-induced gamma oscillations observed in these neurons (Fisahn et al, 2004).…”

“…These receptors have been shown to both mediate and modulate synaptic transmission in both the central and peripheral nervous system (for reviews see (Chittajallu et al, 1999, Frerking and Nicoll, 2000, Lerma et al, 2001, Lerma, 2003, Lerma, 2006, Pinheiro and Mulle, 2006). Regarding the mediation of synaptic transmission, functional postsynaptic KARs have been demonstrated in a variety of cell types (Castillo et al, 1997, Vignes and Collingridge, 1997, Cossart et al, 1998, Frerking et al, 1998, DeVries and Schwartz, 1999, Kidd and Isaac, 1999, Li et al, 1999, Bureau et al, 2000, Cossart et al, 2002, Ali, 2003, Eder et al, 2003, Vitten et al, 2004, Wu et al, 2005, Jin et al, 2006 and may impose unique integrative properties to neurons (Frerking and Ohliger-Frerking, 2002). Furthermore, the expression of postsynaptic KARs has been shown to be restricted in a cellular and subcellular manner.…”