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Ca2+ influx through glutamate receptor-associated channels in retina cells correlates with neuronal cell death

Ferreira, I L ; Duarte, C B ; Carvalho, A P

European journal of pharmacology, 29 April 1996, Vol.302(1-3), pp.153-62 [Periódico revisado por pares]

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  • Título:
    Ca2+ influx through glutamate receptor-associated channels in retina cells correlates with neuronal cell death
  • Autor: Ferreira, I L ; Duarte, C B ; Carvalho, A P
  • Assuntos: 6-Cyano-7-Nitroquinoxaline-2,3-Dione -- Pharmacology ; Calcium -- Metabolism ; Calcium Channels -- Metabolism ; Cell Death -- Physiology ; Excitatory Amino Acid Antagonists -- Pharmacology ; Glutamic Acid -- Pharmacology ; Kainic Acid -- Pharmacology ; N-Methylaspartate -- Pharmacology ; Receptors, Glutamate -- Metabolism ; Retina -- Physiology
  • É parte de: European journal of pharmacology, 29 April 1996, Vol.302(1-3), pp.153-62
  • Descrição: 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.
  • Idioma: Inglês

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