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

Naofumi Tokutomi, Yoshihisa Ozoe, Norihiro Katayama, Akaike Norio

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Effects of lindane (γ-benzenehexachloride; γ-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 × 10-6M, 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 × 10-7M of γ-BHC, only the plateau component of IGABAat 10-5M were depressed without changing the peak amplitude. While γ-BHC at high concentration (> 3 × 10-5M) depressed both the peak and plateau current components. The γ-BHC-induced depression of IGABA seemed to be IGABA-component-dependent. A detailed analysis of the γ-BHC action in the concentration-response relationship for GABA revealed that the IGABA with strong desensitization was preferentially blocked by γ-BHC (> 3 × 10-5M). The rate of recovery of the IGABA from γ-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 γ-BHC-sensitive and -resistant ones. The interposed application of GABA + γ-BHC during generation of IGABA has shown that γ-BHC as well as TBOB or picrotoxin exerted depression of the IGABA under this condition, suggesting that both compounds can act on the GABAA receptor in the activated state. γ-BHC and TBOB were found to compete with picrotoxin in depression of the IGABA. Presence of a specific site within the GABAA receptor-Cl- channel for binding of γ-BHC, TBOB and picrotoxinin, where the convulsants presumably inhibit the Cl--binding.

Original languageEnglish
Pages (from-to)66-73
Number of pages8
JournalBrain research
Volume643
Issue number1-2
DOIs
Publication statusPublished - 1994 Apr 18

Keywords

  • Cl current
  • Dorsal root ganglion neuron
  • Frog
  • GABA receptor
  • Insecticide
  • Lindane
  • Subtype

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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