Desensitization of Kainate Receptors by Kainate, Glutamate and Diastereomers of 4-Methylglutamate

Jones, Kenneth A.; Wilding, Timothy J.; Huettner, James E.; Costa, Anna‐Maria

doi:10.1016/s0028-3908(97)00066-x

Cited by 82 publications

(63 citation statements)

References 38 publications

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“…Moreover, it is well established that the desensitization kinetics of kainate receptors depends of the subunit composition (Swanson et al, 1998b), and that brief exposure to the lectin Con A eliminates desensitization of current gated by kainate and domoate. Using the more selective agonist to kainate receptors (MGA) (Jones et al, 1997;Donevan et al, 1998), we observed that, in the presence of Con A, to eliminate receptor desensitization, MGA did mediate the [Ca 2ϩ ] i increase. Contrary to what happened when cells were stimulated with kainate, the response induced by MGA in the presence of Con A was never inhibited by the AMPA receptor antagonist, LY303070, which further supports the involvement of kainate receptors.…”

Section: Discussionmentioning

confidence: 99%

“…The role of AMPA receptors desensitization on the neuronal viability has been extensively studied recently (Ohno et al, 1997;Ferreira at al., 1998;Ambrósio et al, 2000), but for several years the role of kainate receptors remained elusive. The specific role of kainate receptors as modulators of synaptic transmission has, however already been revealed (Paternain et al, 1995;Jones et al, 1997;Wilding and Huetter, 1997;Malva et al, 1998). The pharmacologic differentiation between active AMPA and kainate receptors was possible due to the development of selective agonists to kainate receptors (Wong et al, 1994;Donevan et al, 1998;Swanson et al, 1998a) and selective AMPA receptor antagonists (Bleakman et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Some kainate receptor agonists, like (5)-5-iodowillardiine (IW) (Swanson et al, 1998a), (R,S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA) (Chittajallu et al, 1999;Johansen et al, 1999) and domoate (Malva et al, 1996;Larm et al, 1997) are extensively used. Recent studies demonstrate, however that (2S,4R)-4-methylglutamate (MGA) is the most potent and selective agonist at kainate receptors (Jones et al, 1997;Donevan et al, 1998), and that it has no effect on AMPA-evoked inward currents in the presence of cyclothiazide (CTZ) in cerebellar granule cells (Savidge et al, 1999). Moreover, it has been shown that Ca 2ϩ influx and subsequent elevation of [Ca 2ϩ ] i is crucial in triggering neuronal death after exposure to excitatory amino acids (Choi, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…We also investigated the [Ca 2ϩ ] i alterations evoked by MGA, because it has been shown that this compound is a potent and selective agonist at kainate receptors, at least for the low concentrations (10 M) utilized (Jones et al, 1997;Donevan et al, 1998). We analyzed 44 neurons in the cultures, and in 86.4% of the cells, the response induced by MGA (10 M) was unmasked in the presence of Con A (Fig.…”

Section: Concanavalin a Unmasks Active Kainate Receptors Upon Stimulamentioning

confidence: 99%

“…Because AMPA and kainate receptors can coexist within a single cell as two independent entities (Partin et al, 1993), in this study, we examined the role of kainate receptors in the [Ca 2ϩ ] i increase, with particular attention to the desensitization of kainate-preferring receptors, and also in the putative neurotoxicity in cultured hippocampal neurons. A selective agonist of kainate receptors (MGA) (Jones et al, 1997;Donevau et al, 1998), and a blocker of receptor desensitization (Con A) were used to evaluate the contribution of kainate receptors to [Ca 2ϩ ] i and toxicity. The role of active kainate receptors in both [Ca 2ϩ ] i changes and excitotoxicity was also elucidated by the direct identification of KA2 and GluR6/7 subunits of kainate receptors by using immunocytochemistry and Western immunoblotting techniques.…”

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confidence: 99%

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Role of kainate receptor activation and desensitization on the [Ca²⁺]_i changes in cultured rat hippocampal neurons

Silva¹,

Malva²,

Ambrósio³

et al. 2001

J of Neuroscience Research

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We investigated the role of kainate (KA) receptor activation and desensitization in inducing the increase in the intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ) in individual cultured rat hippocampal neurons. The rat hippocampal neurons in the cultures were shown to express kainate receptor subunits, KA2 and GluR6/7, either by immunocytochemistry or by immunoblot analysis. The effect of LY303070, an ␣-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, on the alterations in the [Ca 2ϩ ] i caused by kainate showed cell-tocell variability. The [Ca 2ϩ ] i increase caused by kainate was mostly mediated by the activation of AMPA receptors because LY303070 inhibited the response to kainate in a high percentage of neurons. The response to kainate was potentiated by concanavalin A (Con A), which inhibits kainate receptor desensitization, in 82.1% of the neurons, and this potentiation was not reversed by LY303070 in about 38% of the neurons. Also, upon stimulation of the cells with 4-methylglutamate (MGA), a selective kainate receptor agonist, in the presence of Con A, it was possible to observe [Ca 2ϩ ] i changes induced by kainate receptor activation, because LY303070 did not inhibit the response in all neurons analyzed. In toxicity studies, cultured rat hippocampal neurons were exposed to the drugs for 30 min, and the cell viability was evaluated at 24 hr using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The selective activation of kainate receptors with MGA, in the presence of Con A, induced a toxic effect, which was not prevented by LY303070, revealing a contribution of a small subpopulation of neurons expressing kainate receptors that independently mediate cytotoxicity. Taken together, these results indicate that cultured hippocampal neurons express not only AMPA receptors, but also kainate receptors, which can modulate the [Ca 2ϩ ] i and toxicity. J. Neurosci. Res. 65:378 -386, 2001.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Concanavalin a Unmasks Active Kainate Receptors Upon Stimulamentioning

confidence: 99%

mentioning

confidence: 99%

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Role of kainate receptor activation and desensitization on the [Ca²⁺]_i changes in cultured rat hippocampal neurons

Silva¹,

Malva²,

Ambrósio³

et al. 2001

J of Neuroscience Research

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Ionotropic Glutamate Receptors

Bleakman

Alt

Lodge

et al. 2007

Handbook of Contemporary Neuropharmacology

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Since their discovery in the 1950s, ionotropic glutamate receptors represent a class of receptor proteins that mediate fast excitatory transmission in the central nervous system. In this chapter, we describe the extensive studies of agents that act at the various subtypes of ionotropic glutamate receptor and how these agents have been used to delineate the physiological and pathophysiological roles of these receptors.

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Mapping kainate activation of inner neurons in the rat retina

Nivison‐Smith

Sun

Fletcher

et al. 2013

J of Comparative Neurology

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Kainate receptors mediate fast, excitatory synaptic transmission for a range of inner neurons in the mammalian retina. However, allocation of functional kainate receptors to known cell types and their sensitivity remains unresolved. Using the cation channel probe 1-amino-4-guanidobutane agmatine (AGB), we investigated kainate sensitivity of neurochemically identified cell populations within the structurally intact rat retina. Most inner retinal neuron populations responded to kainate in a concentration-dependent manner. OFF cone bipolar cells demonstrated the highest sensitivity of all inner neurons to kainate. Immunocytochemical localization of AGB and macromolecular markers confirmed that type 2 bipolar cells were part of this kainate-sensitive population. The majority of amacrine (ACs) and ganglion cells (GCs) showed kainate responses with different sensitivities between major neurochemical classes (γ-aminobutyric acid [GABA]/glycine ACs > glycine ACs > GABA ACs; glutamate [Glu]/weakly GABA GCs > Glu GCs). Conventional and displaced cholinergic ACs were highly responsive to kainate, whereas dopaminergic ACs do not appear to express functional kainate receptors. These findings further contribute to our understanding of neuronal networks in complex multicellular tissues.

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Desensitization of Kainate Receptors by Kainate, Glutamate and Diastereomers of 4-Methylglutamate

Cited by 82 publications

References 38 publications

Role of kainate receptor activation and desensitization on the [Ca²⁺]_i changes in cultured rat hippocampal neurons

Role of kainate receptor activation and desensitization on the [Ca²⁺]_i changes in cultured rat hippocampal neurons

Ionotropic Glutamate Receptors

Mapping kainate activation of inner neurons in the rat retina

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Desensitization of Kainate Receptors by Kainate, Glutamate and Diastereomers of 4-Methylglutamate

Cited by 82 publications

References 38 publications

Role of kainate receptor activation and desensitization on the [Ca2+]i changes in cultured rat hippocampal neurons

Role of kainate receptor activation and desensitization on the [Ca2+]i changes in cultured rat hippocampal neurons

Ionotropic Glutamate Receptors

Mapping kainate activation of inner neurons in the rat retina

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Role of kainate receptor activation and desensitization on the [Ca²⁺]_i changes in cultured rat hippocampal neurons

Role of kainate receptor activation and desensitization on the [Ca²⁺]_i changes in cultured rat hippocampal neurons