title: Ca2+ influx through glutamate receptor-associated channels in retina cells correlates with neuronal cell death.
abstract: We studied the effect of glutamate, N-methyl-D-aspartate (NMDA), kainate or K+ depolarization, on neurotoxicity in cultured chick retinal cells, under conditions in which we could discriminate between Ca2+ entering through ionotropic glutamate receptors and voltage-sensitive Ca2+ channels (VSCCs). When neurons were challenged with NMDA, kainate or glutamate, in Na(+)-containing medium, a decrease in cell survival was observed, whereas K+ depolarization did not affect the viability of the cells. The Mg2+ ion completely prevented the toxic effect mediated by the NMDA receptor, and had a small but significant protective effect at the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) receptor-induced cell death. We observed that, in a Na(+)-free N-methyl-D-glucamine (NMG) medium, to avoid the activation of VSCCs indirectly by the glutamate receptor agonists, stimulation of the glutamate receptors causes Ca2+ influx only through NMDA and AMPA/kainate receptor-associated channels, and that Ca2+ entry correlates well with subsequent cell death. These results show that the activation of NMDA or AMPA/kainate receptors can cause excitotoxicity in retinal neurons by mechanisms not involving Na+ influx, but rather depending on the permeation of Ca2+ through glutamate receptor-associated channels. For small Ca2+ loads the entry of Ca2+ through the NMDA receptor-associated channel was more efficient in triggering cell death than the influx of Ca2+ through the AMPA/kainate receptor.
authors.affiliation: Center for Neurosciences of Coimbra, Department of Zoology, University of Coimbra, Portugal.
authors.forename: I L
authors.initials: IL
authors.lastname: Ferreira
authors.forename: C B
authors.initials: CB
authors.lastname: Duarte
authors.forename: A P
authors.initials: AP
authors.lastname: Carvalho
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007608:Kainic Acid; D002118:Calcium