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PMID: 2580971 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

gamma-Aminobutyric-acid- and pentobarbitone-gated chloride currents in internally perfused frog sensory neurones.

The Journal of physiology ·Vol. 360 ·1985-03-00 ·Pages 367-86

Akaike N, Hattori K, Inomata N, Oomura Y

Abstract

gamma-Aminobutyric-acid- (GABA) and pentobarbitone-induced Cl- currents (ICl) were studied in isolated frog sensory neurones after suppression of Na+, K+ and Ca2+ currents using a suction-pipette technique combining internal perfusion with voltage clamp. All GABA-sensitive neurones responded to pentobarbitone. Both GABA- and pentobarbitone-induced ICl reversed at the Cl- equilibrium potential (ECl). The dose-response curve for maxima of GABA-induced ICl was sigmoidal with a mean concentration producing a half-maximum response, Ka of 2 X 10(-5) M at a Hill coefficient of 1.8. In the presence of pentobarbitone, the GABA dose-response curve shifted to the left without affecting the saturating maximum current. At high concentrations, both GABA and pentobarbitone could also potentiate the pentobarbitone- and GABA-induced ICl respectively, while pre-treatment with one of the two markedly attenuated currents induced by the other, indicating a 'cross-desensitization'. In the presence of pentobarbitone, the augmented response was voltage dependent and this augmentation was much greater in the inward-current direction than outward. In producing ICl, pentobarbitone and its stereoisomers were potent in the order of (-) isomer greater than (+/-) racemic mixture greater than (+) isomer. A stereospecific facilitatory action of pentobarbitone on GABA responses was also found in the same order. Responses to GABA, homotaurine, taurine, beta-alanine, 5-aminovaleric acid, (+)- and (-)-gamma-amino-beta-hydroxybutyric acid and muscimol were equally enhanced by pentobarbitone, though its action on glycine-induced ICl was less effective. Picrotoxin inhibited the GABA- and pentobarbitone-induced ICl from either side of membrane, while internal application of GABA and pentobarbitone did not exert any effect. It was concluded that pentobarbitone binds to the 'barbiturate receptors' located close to the GABA receptor-Cl- channel complex, and directly affects the GABA-GABA receptor interactions rather than the ionic channels.

MeSH Terms
Action Potentials/drug effects Amino Acids/pharmacology Animals Chlorides/physiology Dose-Response Relationship, Drug Drug Interactions Ganglia, Spinal/cytology In Vitro Techniques Ion Channels/physiology Muscimol/pharmacology Neurons, Afferent/physiology Pentobarbital/pharmacology gamma-Aminobutyric Acid/pharmacology
Chemicals
Amino Acids Chlorides Ion Channels Muscimol gamma-Aminobutyric Acid Pentobarbital
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Akaike N
Hattori K
Inomata N
Oomura Y
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51 references, click to expand
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.1985.sp015622
Published
1985-03-00
Pages
367-86
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1193466
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.1985.sp015622 PMC Full Text View journal details
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