Stimulation of GABA release from retinal horizontal cells by potassium and acidic amino acid agonists.

The release of [3H]GABA from horizontal cells of goldfish retina was studied by biochemical analysis of perfused isolated retina. Retinas were incubated for 15 min in 0.72 microM [3H]GABA, rinsed for 30 min and then perfused with 1 min pulses of increasing concentrations of K+ and acidic amino acid agonists under a variety of conditions. Radioactivity in the perfusate was determined by liquid scintillation spectroscopy. The main findings are: (1) virtually all of the [3H]GABA released by L-glutamate (L-Glu) and L-aspartate (L-Asp) and 50% of the K+-evoked release, is calcium independent; (2) K+-evoked [3H]GABA release is only 10% of that released by L-Glu; (3) threshold [3H]GABA release occurs with 320 microM L-Glu, 1175 microM L-Asp, 4 microM quisqualic acid (QA), 4 microM kainic acid (KA) and 53 microM N-methyl-DL-aspartate (NMDLA); (4) the quisqualate antagonist glutamic acid diethyl ester (GDEE), has no specific inhibitory action on any of the agonists, whereas D-alpha-aminoadipic acid (D alpha AA), an NMDA antagonist, potently inhibits the action of NMDLA and L-Asp; (5) the presence of Mg2+, even at 1 mM, totally inhibits NMDLA and also inhibits the action of L-Glu and L-Asp below 1 mM; (6) D-Asp potentiates the action of L-Glu by 0.6-0.8 log units and completely inhibits the action of L-Asp; (7) L-Asp at a ratio of 3:1 potentiates the effect of L-Glu. From these and other results one concludes that: (a) [3H]GABA release from H1 cells is calcium independent and depends on factors other than passive depolarization, probably sodium; (2) the likely transmitter of red cones is L-Glu acting on quisqualate or kainate receptors, and (3) L-Asp acts predominantly on NMDA receptors and may provide a modulatory role in the outer retina by potentiating the action of L-Glu.