Multiple actions of dieldrin and lindane on the GABAAreceptor-chloride channel complex of rat dorsal root ganglion neurons

Abstract

The GABA A receptor-chloride channel complex is known to be the target of cyclodiene insecticides and of γ-hexachlorocyclohexane (γ-HCH, lindane). Dieldrin first enhances, then suppresses, γ-aminobutyric acid (GABA)- induced chloride currents, and the latter action results from the acceleration of desensitization. We now report more detailed analyses of the action of dieldrin and γ-HCH on the GABA A receptor-chloride channel complex of rat dorsal root ganglion, using whole-cell and single-channel patch clamp techniques. Preapplication of dieldrin suppressed GABA-induced chloride currents in a time and dose-dependent manner. No enhancement of current was observed under these conditions, because the enhancing action of dieldrin, which is transient in nature, had ceased by the time GABA-induced currents were recorded. Both transient and sustained components of chloride currents were suppressed by dieIdrin. The effect was almost irreversible, and the current did not recover after 30 min of washout with dieldrin-free solution. The currents activated by higher concentrations of GABA were more strongly suppressed by dieldrin. Coapplication of γ-HCH with GABA caused an enhancement of the GABA-induced chloride currents, which was followed by suppression. Single-channel currents induced by 1 μm GABA were completely suppressed by 1 μm γ-HCH. Hyperexcitation of the nervous system and whole animal caused by dieldrin and γ-HCH is the result of suppression of the GABA receptor-chloride channel complex