Kainate receptors

Abstract

Kainate receptors form a family of ionotropic glutamate receptors that appear to play a special role in the regulation of the activity of synaptic networks. This review first describes briefly the molecular and pharmacological properties of native and recombinant kainate receptors. It then attempts to outline the general principles that appear to govern the function of kainate receptors in the activity of synaptic networks under physiological conditions. It subsequently describes the way that kainate receptors are involved in synaptic integration, synaptic plasticity, the regulation of neurotransmitter release and the control of neuronal excitability, and the manner in which they might play an important role in synaptogenesis and synaptic maturation. These functions require the proper subcellular localization of kainate receptors in specific functional domains of the neuron, necessitating complex cellular and molecular trafficking events. We show that our comprehension of these mechanisms is just starting to emerge. Finally, this review presents evidence that implicates kainate receptors in pathophysiological conditions such as epilepsy, excitotoxicity and pain, and that shows that these receptors represent promising therapeutic targets.

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

“…Therefore, our results indicate that KARs mediate approximately 12-14% of the non-NMDA EPSC peak in NS neurons of Layer III. This estimated value is slightly larger than those reported for other neurons where KAR EPSCs have been shown (≤ 10% in response to a single stimulation) (Lerma, 2003,Marchal and Mulle, 2004,Pinheiro and Mulle, 2006.…”

“…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).…”

Polymorphisms in GRIK4, HTR2A, and FKBP5 Show Interactive Effects in Predicting Remission to Antidepressant Treatment

“…These subunits act as tetrameric assemblies pre-and post-synaptically. Kainate receptors are involved in the regulation of neurotransmitter release, fast excitatory neurotransmission, in the control of neuronal excitability, and in synaptic integration and plasticity (Pinheiro and Mulle, 2006). Glutamatergic abnormalities have been reported in plasma (Altamura et al, 1993;Hashimoto et al, 2007), cerebrospinal fluid (Levine et al, 2000;Frye et al, 2007), brain tissue (Francis et al, 1989;Hashimoto et al, 2007), and in brain imaging studies (Auer et al, 2000;de Graaf et al, 2003) of individuals affected with mood disorders.…”

Ethanol inhibition of kainate receptor-mediated excitatory neurotransmission in the rat basolateral nucleus of the amygdala

“…There are three major subtypes of ionotropic glutamate receptors: NMDA, AMPA and kainate-type (KA-R). While the physiological role of AMPA and NMDA receptors in the amygdala with respect to alcohol have been fairly well characterized, the role of KA-Rs in mediating the effects of ethanol has only begun to emerge with the development of pharmacological tools that have allowed the separation of AMPA-and KA-receptor mediated responses (reviewed in (Pinheiro and Mulle, 2006). For example, KA-Rs contribute to postsynaptic glutamatergic excitatory responses in the BLA (Li and Rogawski, 1998) and also mediate a form of long-lasting heterosynaptic facilitation in this brain region (Li et al, 2001).…”