ACTIVITY AT THE GABA TRANSPORTER CONTRIBUTES TO ACUTE CELLULAR SWELLING PRODUCED BY METABOLIC IMPAIRMENT IN RETINA

The role of the GABA transporter in acute toxicity in chick retina due to metabolic inhibition was investigated by the use of several substr ate (nipecotic acid, THPO) and nonsubstrate (SKF89976A, NO711) GABA tr ansport inhibitors, Metabolic stress-induced acute toxicity in the ret ina is characterized by swelling of distinct populations of retinal ne urons and selective release of GABA into the medium, Inhibitor concent rations were based on that needed to attenuate C-14-GABA uptake at its approximate KM concentration by greater than or equal to 70%. Under b asal conditions, substrate, but not nonsubstrate, inhibitors increased extracellular GABA, but did not cause histological swelling per se. U nder conditions of glycolytic inhibition, nonsubstrate, but not substr ate, inhibitors significantly attenuated acute toxicity. Metabolic str ess-induced acute toxicity was not altered by the GABA agonist muscimo l, nor did muscimol reverse the protective effects of nonsubstrate tra nsport not a inhibitors, suggesting that an increase in extracellular GABA during metabolic stress was component of the acute phase of toxci ty. The results indicate that during metabolic inhibition, activity at the GABA transporter contributes to acute cellular swelling. (C) 1997 Elsevier Science Ltd.