Effects of lindane (gamma-BHC) and related convulsants on GABAA receptor-operated chloride channels in frog dorsal root ganglion neurons.
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)
Tokutomi
N
N
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
Ozoe
Y
Y
Katayama
N
N
Akaike
N
N
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D005727:Ganglia, Spinal / Q000502:physiology*; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D011892:Rana catesbeiana; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D003292:Convulsants; D001556:Hexachlorocyclohexane; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C046308:tert-butylbicyclo-2-benzoate