DEVELOPMENTAL EXPRESSION AND SELF-REGULATION OF CA2+ ENTRY VIA AMPA KA RECEPTORS IN THE EMBRYONIC CHICK RETINA/

Excessive activation of glutamate receptors in the late embryonic and adult retina leads to excitotoxic cell death through an increase in in tracellular calcium concentration. Here we use the cobalt-staining tec hnique of Pruss et al. to investigate the developmental. expression of Ca2+-permeable pha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic aci d/kainate (AMPA/KA) receptors in the embryonic chick retina, and the e ffects of AMPA/KA receptor activation on cell survival and AMPA/KA rec eptor expression. Ca2+-permeable AMPA/KA receptors are present in the retina as early as embryonic day 6 (E6). While sustained activation of these receptors with KA led to massive cell death in explant and diss ociated cultures of the chick retina late in development, continuous a pplication of high doses of KA from early times was not excitotoxic. C ell survival in KA is correlated with both a reduction in cobalt stain ing and the KA-evoked membrane current, and thus with a reduction in t he Ca2+ entry into cells via AMPA/KA receptors. The effects of KA coul d be blocked by the non-N-methyl-D-aspartic acid (NMDA) receptor antag onist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), but not by the NMD A receptor antagonist D-2-amino-5-phosphonovalerate (AP5) nor the L-ty pe Ca2+ channel blockers diltiazem and nifedipine. The action of AP5 w as mimicked by exposure to glutamate but not by the metabotropic recep tor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid. Thus expo sure of retinal neurons to glutamate early in development may protect them from its excitotoxic actions later on.