Kainate receptors roles

Whereas the role of AMPA and NMDA receptors in fast synaptic transmission is well characterized, only few examples demonstrating synaptic responses due to kainate receptor activation are known so far. 

Gray A, Allison C, Pratt JA A role for AMPA/kainate receptors in conditioned place preference induced by diazepam in the rat. Neurosci Lett 268 127-130, 1999... 

The role of the kainate receptor system in the brain is at an early stage since there are as yet few pharmacological tools to study its function. However, mutations in the kainate receptor genes have been made in mice and there is a GluR6 kainate receptor knock-out mouse. Kainate binding is absent in areas of the brain which normally have high levels such as the hippocampus. Here, in normal animals kainate receptors mediate a postsynaptic current which is absent in the GluR6 knock-out mouse. The mice have... 

Delineation of the Physiological Role of Kainate Receptors by Use of Subtype Selective Ligands... 

The recently developed GLUK5 selective compound LY382884 (47) is the first antagonist that is selective enough for kainate receptors over AMPA receptors to be used to study the functions of native KA receptors in the presence of intact AMPA receptor-mediated transmission. The use of LY382884 has uncovered a role for kainate receptors in the regulation of short- and long-term synaptic plasticity in the mossy-fiber pathway (49,77) as well as at thalamocortical synapses (87) (Fig. 3)... 

Kainate receptors have recently been implicated in the induction of EIP in the mossy fibers (49,85). Unlike EIP in the area CA1, induction of mossy-fiber EIP is independent of NMDA-receptor activation and involves presynaptic mechanisms (105). Synaptic activation of the facilitatory presynaptic receptor can account for the role of KA receptors in the induction of mossy-fiber LIP by maintaining a high level of release during high-frequency transmission (77). Furthermore, following induction of LTP, the presynaptic kainate receptor-mediated facilitation of synaptic transmission is lost, suggesting that the mechanism by which presynaptic kainate receptors facilitate... 

Kidd, F. L. and Isaac, J. T. (2001) Kinetics and activation of postsynaptic kainate receptors at thalamocortical synapses role of glutamate clearance../. Neurophysiol. 86,1139-1148. 

Four main types of glutamate receptor have been identified and cloned. These are the ionotropic receptors (NMDA and alpha-amino-3-hydroxy-5-methylisoxazole, AMP A, and kainate types) and a group of metabotropic receptors of which eight types have been discovered. The AMP A and kainate receptors are involved in fast excitatory transmission whereas the NMDA receptors mediate slower excitatory responses and play a more complex role in mediating synaptic plasticity. 

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). 

The role of non-NMDA receptor modulators in pain is not as clear as the role of NMDA receptors, but there is evidence to indicate that AMPA and kainate receptors may be involved in nociceptive processing. 

Kainate receptors (KAR) are heteromeric ionotropic glutamate receptors that play a variety of roles in the regulation of synaptic network activity. KAR are composed of five different subunits designated as GluR5, GluR6, GluR7, KA1, and KA2. These subunits have molecular masses of 100 kDa. The primary structure of KA... 

Glutamate Decreased presynaptic markers Decreased HC AMPA and kainate receptor expression Minor changes in FC NMDA R sub-units Altered glutamate fibres in cingulate cortex NMDA receptor antagonists produce schizophrenia-like psychosis Roles of NMDA receptors in development and neurotoxicity Partial NMDA receptor agonists have some therapeutic benefits... 

Lerma, J. (2003). Roles and rules of kainate receptors in synaptic transmission. Nat. Rev. Neurosci. 4,... 

Rodriguez-Moreno A. 2006. The role of kainate receptors in the regulation of excitatory synaptic transmission in the hippocampus. Rev Neurol 42 282-287. 

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