Selective stimulation of excitatory amino acid receptor subtypes and the survival of granule cells in culture: effect of quisqualate and AMPA

Abstract Differentiating granule cells develop survival requirements in vitro which can be met by treatment with high K + or excitatory amino acids. Promotion of cell survival by N -methyl- d -aspartate (NMDA) or kainate has already been established and here we report that treatment of the cells with α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) or quisqualate (QA) also leads to cell rescue. In comparison with the effect of NMDA, the influence of AMPA/QA is small, resulting in a 20–30% increase in cell survival, with a peak at a very narrow concentration range (0.5–2.0 μM QA and 5–10 μM AMPA). The effect is exclusive to AMPA receptor stimulation, since stimulation of metabotropic glutamate receptors with (1 S 3 R )-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) has no effect. Furthermore, AMPA/QA rescue of cells is blocked by ionotropic non-NMDA receptor antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline (NBQX). In addition, both nifedipine and dizolcipline (MK-801) interfered with the cell survival promoting effect of AMPA, suggesting that the influence of AMPA is mediated via calcium influx involving both depolarization-activated voltage sensitive calcium channels and NMDA receptors stimulated as a result of AMPA-induced release of glutamate. Possible reasons for the small cell survival promoting effect of AMPA/QA compared with the influence of high K + or NMDA are discussed.