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

研究成果: Article査読

18 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)66-73
ページ数8
ジャーナルBrain research
643
1-2
DOI
出版ステータスPublished - 1994 4月 18
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)
  • 分子生物学
  • 臨床神経学
  • 発生生物学

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