Glutamate increases the [Ca2+]i but stimulates Ca(2+)-independent release of [3H]GABA in cultured chick retina cells.

The effect of glutamate on [Ca2+]i and on [3H] gamma-aminobutyric acid (GABA) release was studied on cultured chick embryonic retina cells. It was observed that glutamate (100 microM) increases the [Ca2+]i by Ca2+ influx through Ca2+ channels sensitive to nitrendipine, but not to omega-conotoxin GVIA (omega-Cg Tx) (50%), and by other channels insensitive to either Ca2+ channel blocker. Mobilization of Ca2+ by glutamate required the presence of external Na+, suggesting that Na+ mobilization through the ionotropic glutamate receptors is necessary for the Ca2+ channels to open. The increase in [Ca2+]i was not related to the release of [3H]GABA induced by glutamate, suggesting that the pathway for the entry of Ca2+ triggered by glutamate does not lead to exocytosis. In fact, the glutamate-induced release of [3H]GABA was significantly depressed by Ca(2+)o, but it was dependent on Na(+)o, just as was observed for the [3H]GABA release induced by veratridine (50 microM). The veratridine-induced release could be fully inhibited by TTX, but this toxin had no effect on the glutamate-induced [3H]GABA release. Both veratridine- and glutamate-induced [3H]GABA release were inhibited by 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3-py ridine- carboxylic acid (NNC-711), a blocker of the GABA carrier. Blockade of the NMDA and non-NMDA glutamate receptors with MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively, almost completely blocked the release of [3H]GABA evoked by glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)