Kainate receptor glutamate receptors

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

Using hybridization in situ with oligonucleotide probes, expression patterns of the five known kainate-type glutamate receptor subunit genes, KA1, KA2 and GluR5 to 7, have been discovered in brain tissue of adult and developing rat brain (Michaelis, 1998 Lerma et al., 2001). In situ hybridization studies also indicate that neurons showing the KA1 response are almost exclusively restricted to the CA3... 

Cu is normally found at relatively high levels in the brain (100-150 xM) with substantial variations at the cellular and subcellular level [55-57]. Ionic Cu is compartmentalized into a post-synaptic vesicle and released upon activation of the NMDA-R but not AMPA/kainate-type glutamate receptors [58]. The Menkes Cu7aATPase is the vesicular membrane Cu transporter, and upon NMDA-R activation, it traffics rapidly and reversibly to neuronal processes, independent of the intracellular Cu concentration [58]. Cu ions function to suppress NMDA activation and prevent excitotoxicity by catalyzing S-nitrosylation of specific cysteine residues on the extracellular domain of the NRl and NR2A subunits of the NMDA receptor [58]. The concentrations of Cu in the synaptic cleft can reach approximately 15 xM. Subsequently, Cu is cleared by uptake mechanisms from the synaptic cleft. Several studies have shown that Cu levels increase with age in the brains of mice [22-24]. 

Egebjerg, J. and Heinemann, S.E., Ca permeability of unedited and edited versions of the kainate selective glutamate receptor GluR6, Proc. Natl. Acad. Sci. USA, 90, 755, 1993. 

Glutamate receptor. agonists ( excitotoxins ) glutamate, kainate,... 

Lerma J (1999) Kainate receptors, chapter 8 Ionotropic glutamate receptors in the CNS. Springer Verlag... 

Kainate receptors are a subtype of ionotropic glutamate receptors that are permeable to Na+, K+ and Ca2+ ions. 

Non-NMDA ionotropic glutamate receptors (the majority sodium channel containing) can be subdivided into a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) (comprising cloned subunits GluRl ) and kainate (GluR5-7, KAl-2) preferring receptors, with native receptors most likely to comprise either homo- or heteromeric pentamers of these subunits. 

Dingledine, R et al. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51 7-61. Frerking, M and Nicoll, RA (2000) Synaptic kainate receptors. Curr. Opin. Neurobiol. 10 342-351. Gegelashvili, G and Schousboe, A (1997) High affinity glutamate transporters regulation of expression and activity. Mol. Pharmacol. 52 6-15. 

Hollman, M and Heinemann, S (1994) Cloned glutamate receptors. Arm. Rev. Neurosci. 17 31-108. Lerma, J (1997) Kainate reveals its targets. Neuron 19 1155-1158. 

FIGURE 3.8 Kainate and AMPA activate different current responses in the different classes of kainate and AMPA receptors (a) the AMPA receptor, GluRl (b) and (c) kainate receptors (d) glutamate + glycine activation of the NMDA receptor. The current response is characterized by a slow onset and offset compared to the kainate and AMPA receptors. 

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