Effects of lindane (gamma-BHC) and related convulsants on GABAA receptor-operated chloride channels in frog dorsal root ganglion neurons

Brain Res. 1994 Apr 18;643(1-2):66-73. doi: 10.1016/0006-8993(94)90009-4.

Abstract

Effects of lindane (gamma-benzenehexachloride; gamma-BHC) on GABA-evoked Cl- current (IGABA) in freshly dissociated frog sensory (dorsal root ganglion) neurons were studied and compared with those of tert-butylbicycloortho benzoate (TBOB) and picrotoxin by the use of the suction-pipette method [13]. Drugs were applied with a rapid drug-application method, "Concentration-clamp" technique. At concentration of GABA of > 3 x 10(-6) M, at least two components of the IGABA were recognized distinct degree of desensitization. Those were defined as the peak and plateau components in the text. At low concentration (3 x 10(-7) M) of gamma-BHC, only the plateau component of IGABA at 10(-5) M were depressed without changing the peak amplitude. While gamma-BHC at high concentration (3 x 10(-5) M) depressed both the peak and plateau current components. The gamma-BHC-induced depression of IGABA seemed to be IGABA-component-dependent. A detailed analysis of the gamma-BHC action in the concentration-response relationship for GABA revealed that the IGABA with strong desensitization was preferentially blocked by gamma-BHC (3 x 10(-5) M). The rate of recovery of the IGABA from gamma-BHC-induced block depended on the concentration of GABA. The lower the concentration of GABA, the slower the recovery. The GABAA receptor Cl- channels were proposed to be classified into two types of the gamma-BHC-sensitive and -resistant ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Chloride Channels / drug effects
  • Chloride Channels / physiology*
  • Convulsants / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophysiology / methods
  • Ganglia, Spinal / physiology*
  • Hexachlorocyclohexane / pharmacology*
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Picrotoxin / pharmacology
  • Rana catesbeiana
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology*
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Chloride Channels
  • Convulsants
  • Receptors, GABA-A
  • Picrotoxin
  • gamma-Aminobutyric Acid
  • Hexachlorocyclohexane
  • tert-butylbicyclo-2-benzoate