Glutamate receptor agonists evoked Ca(2+)-dependent and Ca(2+)-independent release of [3H]D-aspartate from cultured chick retina cells.

We studied the release of [3H]D-aspartate evoked by glutamate receptor agonists from monolayer cultures of chick retina cells, and found that activation of the glutamate receptors can evoke both Ca(2+)-dependent and Ca(2+)-independent release of [3H]D-aspartate. In Ca(2+)-free (no added Ca2+) Na+ medium, the agonists of the glutamate receptors induced the release of [3H]D-aspartate with the following rank order of potency: kainate > alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) approximately N-methyl-D-aspartate (NMDA). In media containing 1 mM CaCl2 the release of [3H]D-aspartate evoked by NMDA, kainate and AMPA was increased by about 112 percent, 20 percent and 39 percent, respectively, as compared to the release evoked by the same agonists in Ca(2+)-free medium. NMDA was the most potent agonist in stimulating the Ca(2+)-dependent release of [3H]D-aspartate, possibly by exocytosis, and AMPA was as potent as kainate. The Ca(2+)-dependent release of [3H]D-aspartate evoked by kainate was dependent on the influx of Ca2+ through the receptor associated channel, as well as through the N-(omega-Conotoxin GVIA-sensitive) and L- (nitrendipine-sensitive) type voltage-sensitive Ca2+ channels (VSCC). The exocytotic release of [3H]D-aspartate evoked by AMPA relied exclusively on Ca2+ entry through the L-type VSCC, whereas the effect of NMDA was partially mediated by the influx of Ca2+ through the receptor-associated channel, but not through L- or N-type VSCC. Thus, activation of these different glutamate receptors under physiological conditions is expected to cause the release of cytosolic and vesicular glutamate, and the routes of Ca2+ entry modulating vesicular release may be selectively recruited.