Differential effects of hexachlorocyclohexane isomers on the GABA receptor-chloride channel complex in rat dorsal root ganglion neurons.
The GABAA 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), alpha-, beta-, gamma- and delta-HCH, on the GABAA receptor-chloride channel complex of rat dorsal root ganglion neurons using patch clamp techniques. When co-applied with 10 microM GABA, 1 microM gamma-HCH slightly enhanced and then suppressed the GABA-induced chloride current. The desensitization of the current was greatly accelerated by gamma-HCH in a dose-dependent manner. The acceleration of desensitization and the suppression of sustained component of current by gamma-HCH occurred at lower concentration ranges than those for the suppression of peak current. When 10 microM delta-HCH was co-applied with 10 microM GABA, current was greatly enhanced and then suppressed, and the level of enhancement was much higher than that of gamma-HCH. alpha- and beta-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.
Nagata
K
K
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Narahashi
T
T
D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007306:Insecticides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects*
D018118:Chloride Channels; D007306:Insecticides; D018079:Receptors, GABA; D001556:Hexachlorocyclohexane