LINDANE CYTOTOXICITY IN CULTURED NEOCORTICAL NEURONS IS AMELIORATED BY GABA AND FLUNITRAZEPAM

The effect of lindane (gamma-hexachlorocyclohexane) on [S-35]t-butylbi cyclophosphorothionate ([S-35]TBPS) binding and GABA-stimulated (CI-)- C-36 influx was investigated in cultured cerebral cortical neurons, In addition, the cytotoxic action of lindane as well as a protection by GABA and flunitrazepam were studied together with the ability of linda ne to increase the intracellular concentration of free Ca2+. Lindane w as found to be toxic to the neurons, an effect that could be completel y prevented by the simultaneous presence of GABA (0.1 mu M) and flunit razepam (100 mu M) and reduced by GABA alone, An interaction with the GABA receptor-gated chloride channel was demonstrated by an inhibitory action of lindane on [S-35]TBPS binding (IC50 188 +/- 51 nM) and on G ABA-stimulated (CI-)-C-36 influx in the neurons, Lindane only marginal ly increased the intracellular Ca2+ concentration in the neurons, It i s concluded that the cytotoxic action of lindane is mediated through i nteraction with GABA receptors in a manner essentially independent of changes in intracellular Ca2+ homeostasis. (C) 1994 Wiley-Liss, Inc.