Differential effects of hexachlorocyclohexane isomers on the GABA receptor-chloride channel complex in rat dorsal root ganglion neurons

The GABA_A receptor-chloride channel complex has recently been demonstrated by patch clamp experiments to be the target of cyclodiene insecticides. We have now examined the effects of four isomers of hexachlorocyclohexane (HCH), α-, β-, γ- and δ-HCH, on the GABA_A receptor-chloride channel complex of rat dorsal root ganglion neurons using patch clamp techniques. When co-applied with 10 μM GABA, 1 μM γ-HCH slightly enhanced and then suppressed the GABA-induced chloride current. The desensitization of the current was greatly accelerated by γ-HCH in a dose-dependent manner. The acceleration of desensitization and the suppression of sustained component of current by γ-HCH occurred at lower concentration ranges than those for the suppression of peak current. When 10 μM δ-HCH was co-applied with 10 μM GABA, current was greatly enhanced and then suppressed, and the level of enhancement was much higher than that of γ-HCH. α- and β-HCH had little or no effect on the GABA-induced chloride current. The differential actions of these isomers on GABA-activated chloride currents account for variable symptoms of poisoning in insects and mammals.