Kainate receptor subunits expressed in single cultured hippocampal neurons: Molecular and functional variants by RNA editing

Ruano, Diego; Lambolez, Bertrand; Rossier, Jean; Paternain, Ana V.; Lerma, Juan

doi:10.1016/0896-6273(95)90339-9

Cited by 130 publications

(97 citation statements)

References 34 publications

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“…The results we obtained in oligodendrocytes are apparently in contrast to those observed in hippocampal neurons in vitro, in which the expressed kainate receptors have a very low Ca 2ϩ permeability (21). Yet, kainate receptors in hippocampal neurons are formed principally by the unedited variant Q of the GluR6 subunit (24). It is thus conceivable that cell type specific dependent mechanisms different from editing may account for the putative differences in the Ca 2ϩ permeability of kainate receptors expressed by oligodendrocytes and neurons.…”

Section: Discussioncontrasting

confidence: 55%

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Matute

Sánchez‐Gómez

Martínez‐Millán

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

328

267

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In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription-PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-Daspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population.The main function of oligodendrocytes is to myelinate axons in the vertebrate central nervous system. This cell type develops mostly soon after the majority of neurons are generated and have extended their axons and, therefore, it is likely that neurons play an important role in regulating oligodendrocyte development. In the rat optic nerve, the first fully differentiated oligodendrocytes appear after birth, and the definitive mature population of oligodendrocytes is reached around 6 weeks later (1, 2). The proliferation and the survival of oligodendrocytes depend, respectively, on the electrical activity of neighboring axons and in the reciprocal contacts they establish (for a recent review, see ref.3). Axon to oligodendrocyte signaling results in the generation of the precise number of oligodendrocytes necessary to myelinate entirely a given population of axons. Unfortunately, little information is available about the molecules participating in this signaling process.Oligodendrocytes express neurotransmitter receptors including those activated by glutamate (4). This excitatory amino acid acts at various types of receptors, which can be grouped into two major categories: ionotropic receptors, which gate membrane ion channels permeable to cations; and metabotropic receptors, which are coupled to G proteins. Ionotropic receptors are classified into ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-Daspartate (NMDA) subtypes, according to their preferred agonist. Molecular cloning has revealed that each receptor subtype is composed of several subunits with high homology within each receptor class (reviewed in ref. 5). Thus, AMPA receptors are formed by GluR1-4, kainate receptors by GluR5-7 and KA1-2, and NMDA rece...

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Section: Discussioncontrasting

confidence: 55%

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Matute

Sánchez‐Gómez

Martínez‐Millán

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

328

267

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“…The two steps of multiplex PCR were performed essentially as described previously (Ruano et al, 1995). The cDNAs present in 10 l of the reverse transcription reaction were first amplified simultaneously using the primer pairs described previously (C auli et al, 1997).…”

Section: Methodsmentioning

confidence: 99%

Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors

et al. 1999

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The cellular mechanisms by which neuronal nicotinic cholinergic receptors influence many aspects of physiology and pathology in the neocortex remain primarily unknown. Whole-cell recordings and single-cell reverse transcription (RT)-PCR were combined to analyze the effect of nicotinic receptor agonists on different types of neurons in acute slices of rat neocortex. Nicotinic receptor agonists had no effect on pyramidal neurons and on most types of interneurons, including parvalbuminexpressing fast spiking interneurons and somatostatinexpressing interneurons, but selectively excited a subpopulation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin. This excitation persisted in the presence of glutamate, GABA, and muscarinic receptor antagonists and in the presence of tetrodotoxin and low extracellular calcium, suggesting that the depolarization was mediated through the direct activation of postsynaptic nicotinic receptors. The responses were blocked by the nicotinic receptor antagonists dihydro-␤-erythroidine and mecamylamine and persisted in the presence of the ␣7 selective nicotinic receptor antagonist methyllycaconitine, suggesting that the involved nicotinic receptors lacked the ␣7 subunit. Single-cell RT-PCR analysis indicated that the majority of the interneurons that responded to nicotinic stimulation coexpressed the ␣4, ␣5, and ␤2 nicotinic receptor subunits. Therefore, these results provide a role for non-␣7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical interneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism, these results also provide a cellular basis for the neuronal regulation of cortical blood flow mediated by acetylcholine. Key words: single-cell PCR; neuropeptides; calcium-binding proteins; methyllycaconitine; dihydro-␤-erythroidine; acetylcholine; mecamylamineNicotinic receptors are implicated in many important f unctions of the mammalian neocortex, including memory formation (Granon et al., 1995) and neuronal regulation of regional cerebral blood flow (Gitelman and Prohovnik, 1992;Uchida et al., 1997), as well as cortical pathologies such as Alzheimer's disease (Whitehouse et al., 1988;Newhouse et al., 1997), epilepsy (Steinlein et al., 1995, and Tourette's syndrome (Sanberg et al., 1997(Sanberg et al., , 1998. The cellular basis for the effects of nicotinic receptor stimulation is currently unknown but lies within its effects on the complex interactions between the excitatory glutamatergic pyramidal neurons and the inhibitory interneurons.A variety of different neuronal nicotinic receptor subunits have been cloned and named ␣2-␣9 and ␤2-␤4 (Elgoyhen et al., 1994;Le Novere and Changeux, 1995). C lassically, two broad subfamilies of nicotinic receptors have been characterized in neurons according to their sensitivity to ␣-bungarotoxin. Subunits ␣7 and ␣8 form a family of ␣-bungarotoxin-sensitive channels (Couturier...

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“…However, only a fraction of AMPA receptors exhibit Ca2~per-meability (Hollman et al, 1991;Gasic and Heinemann, 1992;Bochet et al, 1994;Jonas et al, 1994;Ruano et al, 1995). Neurons bearing Ca2-permeable channels can be identified immunohistochemically using kainate-activated cobalt uptake, and would be vulnerable to Ca2~neurotoxicity through AMPA receptors (Pruss et al, 1991;Turetsky et al, 1994).…”

Section: Figmentioning

confidence: 99%

Distinct Influx Pathways, Not Calcium Load, Determine Neuronal Vulnerability to Calcium Neurotoxicity

Sattler¹,

Charlton

Hafner

et al. 1998

Journal of Neurochemistry

246

192

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Many forms of neurodegeneration are ascribed to excessive cellular Ca 2~loading (Ca2~hypothesis). We examined quantitatively whether factors other than 1Ca 2l oading were determinants of excitotoxic neurode~'eneration. Cell survival, morphology, free intracellular Cas1 concentration ([Ca2~]), and 45Ca2~accumulation were measured in cultured cortical neurons loaded with known quantities of Ca2through distinct transmembrane pathways triggered by excitatory amino acids, cell membrane depolarization, or Ca2ĩonophores. Contrary to the Ca2h ypothesis, the relationships between Ca2~load and cell survival, free [Ca2~]~, and Ca2~-inducedmorphological alterations depended primarily on the route of Ca2~influx, not the Ca2~load. Notably, Ca2~loading via NMDA receptor channels was toxic, whereas identical Ca2~loads incurred through voltage-sensitive Ca2~channels were completely innocuous. Furthermore, accounting quantitatively for Ca2~loading via NMDA receptors uncovered a previously unreported component of L-glutamate neurotoxicity apparently not mediated by ionotropic or metabotropic glutamate receptors. lt was synergistic with toxicity attributable to glutamate-evoked Ca2~loading, and correlated with enhanced cellular ATP depletion. This previously unrecognized toxic action of glutamate constituted a chief excitotoxic mechanism under conditions producing submaximal Ca2~loading. We conclude that (a) Ca2~neurotoxicity is a function of the Ca2~infltlx pathway, not Ca2 load, and (b) glutamate toxicity may not be restricted to its actions on glutamate receptors.

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Kainate receptor subunits expressed in single cultured hippocampal neurons: Molecular and functional variants by RNA editing

Cited by 130 publications

References 34 publications

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors

Distinct Influx Pathways, Not Calcium Load, Determine Neuronal Vulnerability to Calcium Neurotoxicity

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