Home LiteratureArticle Details
PMID: 6273918 Published · ppublish English Journal Article

Diazepam and (--)-pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of gamma-aminobutyric acid responses in cultured central neurons.

Study RE, Barker JL

Abstract

Diazepam and (--)-pentobarbital each potentiate the increase in chloride ion conductance produced by gamma-aminobutyric acid (GABA) i voltage-clamped mouse spinal neurons grown in culture. Fluctuation analysis was used to compare the properties of elementary ion-channel events underlying the chloride conductance produced by GABA alone and during potentiation by the two drugs. Neither drug altered the conductance of an open ion channel, but both drugs affected the kinetics of channel activity. Diazepam increased the frequency of channel openings and either did not affect or slightly increased the average open-channel lifetime, whereas (--)-pentobarbital decreased the frequency of channel openings and increased average open-channel lifetime. These changes in the kinetics of GABA-activated ion channels can quantitatively account for the potentiation of GABA responses observed with the drugs. Thus, the drugs each increase the response to GABA but do not act on channel kinetics in the same manner.

MeSH Terms
Animals Cells, Cultured Diazepam/pharmacology Embryo, Mammalian Ion Channels/physiology Membrane Potentials/drug effects Mice Mice, Inbred C57BL Neurons/drug effects,physiology Pentobarbital/pharmacology Spinal Cord/physiology gamma-Aminobutyric Acid/pharmacology
Chemicals
Ion Channels gamma-Aminobutyric Acid Pentobarbital Diazepam
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Study R E
Barker J L
References (22)
22 references, click to expand
  1. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction.
    J Physiol. 1973 Dec;235(3):655-91 PMID: 4543940
  2. PHARMACOLOGICAL STUDIES ON PRESYNAPTIC INHIBITION.
    J Physiol. 1963 Oct;168:500-30 PMID: 14067941
  3. Pentobarbital: action on frog motoneurons.
    Brain Res. 1975 Oct 10;96(1):119-23 PMID: 1174993
  4. Conductance fluctuations and ionic pores in membranes.
    Annu Rev Biophys Bioeng. 1977;6:345-81 PMID: 68708
  5. Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties.
    J Neurophysiol. 1977 Sep;40(5):1132-50 PMID: 333062
  6. Fluctuation analysis in neurobiology.
    Int Rev Neurobiol. 1977;20:169-208 PMID: 304052
  7. Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones.
    Nature. 1978 Feb 9;271(5645):563-4 PMID: 563985
  8. Life time and elementary conductance of the channels mediating the excitatory effects of acetylcholine in Aplysia neurones.
    J Physiol. 1978 May;278:177-206 PMID: 671284
  9. GABA-induced conductance fluctuations in cultured spinal neurones.
    Nature. 1978 Aug 10;274(5671):596-7 PMID: 672992
  10. Amino acid pharmacology of mammalian central neurones grown in tissue culture.
    J Physiol. 1978 Jul;280:331-54 PMID: 690884
  11. Pentobarbitone pharmacology of mammalian central neurones grown in tissue culture.
    J Physiol. 1978 Jul;280:355-72 PMID: 690885
  12. Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action.
    Brain Res. 1979 May 11;167(2):323-36 PMID: 445132
  13. Molecular mechanisms in the receptor action of benzodiazepines.
    Annu Rev Pharmacol Toxicol. 1979;19:531-45 PMID: 36830
  14. Pentobarbital: stereospecific actions of (+) and (-) isomers revealed on cultured mammalian neurons.
    Science. 1980 Jan 11;207(4427):195-7 PMID: 7350656
  15. Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells.
    J Physiol. 1979 Oct;295:139-70 PMID: 42780
  16. Voltage clamp study of fast excitatory synaptic currents in bullfrog sympathetic ganglion cells.
    J Gen Physiol. 1980 Jan;75(1):39-60 PMID: 6965707
  17. Phenobarbitone modulation of postsynaptic GABA receptor function on cultured mammalian neurons.
    Proc R Soc Lond B Biol Sci. 1979 Dec 31;206(1164):319-27 PMID: 43977
  18. Single-shot channel activation accounts for duration of inhibitory postsynaptic potentials in a central neuron.
    Science. 1980 May 9;208(4444):612-5 PMID: 6245449
  19. Inhibitory synaptic channels activated by gamma-aminobutyric acid (GABA) in crayfish muscle.
    Pflugers Arch. 1980 Sep;387(2):143-51 PMID: 7191978
  20. Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture.
    J Neurophysiol. 1981 Apr;45(4):621-31 PMID: 6262463
  21. Enhancement of GABA binding by pentobarbitone.
    Neurosci Lett. 1980 Jul;18(3):323-7 PMID: 6302591
  22. Pentobarbital modulates transmitter effects on mouse spinal neurones grown in tissue culture.
    Nature. 1975 Apr 24;254(5502):703-5 PMID: 1124130
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1981-11-00
Pages
7180-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC349220
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]