EFFECTS OF ORGANOCHLORINE PESTICIDES ON CL-36(-) FLUX IN PRIMARY NEURONAL CULTURES

Primary cultures from cortical neuronal cells were used to study the e ffect of organochlorine pesticides on GABA-dependent Cl- fluxes. In th is system cyclodienes inhibited GABA-induced Cl-36(-) uptake with simi lar potencies to those described using brain synaptoneurosomes whereas lindane showed greater potency than that described using other in vit ro systems. Basal Cl- uptake was not affected by these compounds altho ugh a-endosulfan exhibited a small inhibition. DDT, which mechanism of neurotoxic action has been postulated through activation of Na+ chann els, did not inhibit GABA-induced Cl-36(-) uptake. These results clear ly demonstrate that the stimulant neurotoxic effects of cyclodienes an d lindane are produced by their interaction with the Cl- channel coupl ed to the GABA(A) receptor. Furthermore, these results show the useful ness of cortical neuronal cultures to study the effects of toxic agent s on GABAA receptor. (C) 1994 Intox Press, Inc.