Nagata K, Narahashi T
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Brain Res. 1995 Dec 15;704(1):85-91. doi: 10.1016/0006-8993(95)01108-0.
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.
GABAA受体-氯离子通道复合物最近通过膜片钳实验被证明是环二烯类杀虫剂的作用靶点。我们现在使用膜片钳技术研究了六氯环己烷（HCH）的四种异构体，即α-、β-、γ-和δ-HCH，对大鼠背根神经节神经元GABAA受体-氯离子通道复合物的影响。当与10微摩尔/升的GABA共同应用时，1微摩尔/升的γ-HCH先轻微增强然后抑制GABA诱导的氯离子电流。γ-HCH以剂量依赖的方式极大地加速了电流的脱敏过程。γ-HCH对脱敏的加速作用以及对电流持续成分的抑制作用发生的浓度范围低于对峰值电流的抑制浓度范围。当10微摩尔/升的δ-HCH与10微摩尔/升的GABA共同应用时，电流先大幅增强然后被抑制，且增强程度远高于γ-HCH。α-和β-HCH对GABA诱导的氯离子电流几乎没有影响。这些异构体对GABA激活的氯离子电流的不同作用解释了昆虫和哺乳动物中毒症状的差异。
