DOMOIC ACID-INDUCED RELEASE OF [H-3] GABA IN CULTURED CHICK RETINA CELLS

The effect of the neurotoxin domoic acid (DOM), a structural analogue of kainic acid, on the release of [H-3]gamma-aminobutyric acid (GABA) and on the [Ca2+]i was studied in cultured chick retina cells. DOM sti mulated dose-dependently the release of [H-3]GABA with an EC50 of 2.5 muM. In Ca2+-containing medium (1 mM). DOM (5 muM) increased the [Ca2]i by about 190 nM and evoked the release of 11.8 +/- 1.3% of the intr acellular [H-3]GABA, while in the absence of extracellular Ca2+ DOM in duced the release of only 7.9 +/- 1.4% of the accumulated [H-3]GABA. T he Ca2+-independent release of [H-3]GABA was blocked by the non-compet itive inhibitor of the GABA carrier xy)ethyl)-1,2,5,6-tetrahydro-3-pyr idine-carboxylic acid hydrochloride (NNC-711), but a component of Ca2-dependent release remains. DOM evoked Ca2+-independent release of [H- 3]GABA was significantly depressed in the absence of external Na+ and completely blocked by the non-selective antagonist of the non-NMDA glu tamate receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Similar ly, CNQX decreased the [Ca2+]i response to DOM, whereas L(+)-2-amino-3 -phosphonopropionic acid (L-AP3), an antagonist of the metabotropic gl utamate receptors, was without effect. MK-801 did not affect the relea se of [H-3]GABA stimulated by DOM. Taken together our results indicate that DOM evokes both Ca2+-dependent and Ca2+-independent release of [ H-3]GABA, most likely by activating kainate receptors.