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Hippocampal GABA(A) channel conductance increased by diazepam

Eghbali, M ; Curmi, J P ; Birnir, Bryndis LU and Gage, P W (1997) In Nature 388(6637). p.71-75
Abstract
Benzodiazepines, which are widely used clinically for relief of anxiety and for sedation, are thought to enhance synaptic inhibition in the central nervous system by increasing the open probability of chloride channels activated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here we show that the benzodiazepine diazepam can also increase the conductance of GABAA channels activated by low concentrations of GABA (0.5 or 5 microM) in rat cultured hippocampal neurons. Before exposure to diazepam, chloride channels activated by GABA had conductances of 8 to 53pS. Diazepam caused a concentration-dependent and reversible increase in the conductance of these channels towards a maximum conductance of 70-80 pS and the effect was... (More)
Benzodiazepines, which are widely used clinically for relief of anxiety and for sedation, are thought to enhance synaptic inhibition in the central nervous system by increasing the open probability of chloride channels activated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here we show that the benzodiazepine diazepam can also increase the conductance of GABAA channels activated by low concentrations of GABA (0.5 or 5 microM) in rat cultured hippocampal neurons. Before exposure to diazepam, chloride channels activated by GABA had conductances of 8 to 53pS. Diazepam caused a concentration-dependent and reversible increase in the conductance of these channels towards a maximum conductance of 70-80 pS and the effect was as great as 7-fold in channels of lowest initial conductance. Increasing the conductance of GABAA channels tonically activated by low ambient concentrations of GABA in the extracellular environment may be an important way in which these drugs depress excitation in the central nervous system. That any drug has such a large effect on single channel conductance has not been reported previously and has implications for models of channel structure and conductance. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature
volume
388
issue
6637
pages
71 - 75
publisher
Nature Publishing Group
external identifiers
  • pmid:9214504
  • scopus:0030848203
  • pmid:9214504
ISSN
0028-0836
DOI
10.1038/40404
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: GABA Channels in Physiology and Pharmacology (013241570)
id
be30e370-9dae-4d8d-a31c-1e1a83f313bd (old id 1111679)
date added to LUP
2016-04-01 11:34:00
date last changed
2022-03-05 03:18:54
@article{be30e370-9dae-4d8d-a31c-1e1a83f313bd,
  abstract     = {{Benzodiazepines, which are widely used clinically for relief of anxiety and for sedation, are thought to enhance synaptic inhibition in the central nervous system by increasing the open probability of chloride channels activated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here we show that the benzodiazepine diazepam can also increase the conductance of GABAA channels activated by low concentrations of GABA (0.5 or 5 microM) in rat cultured hippocampal neurons. Before exposure to diazepam, chloride channels activated by GABA had conductances of 8 to 53pS. Diazepam caused a concentration-dependent and reversible increase in the conductance of these channels towards a maximum conductance of 70-80 pS and the effect was as great as 7-fold in channels of lowest initial conductance. Increasing the conductance of GABAA channels tonically activated by low ambient concentrations of GABA in the extracellular environment may be an important way in which these drugs depress excitation in the central nervous system. That any drug has such a large effect on single channel conductance has not been reported previously and has implications for models of channel structure and conductance.}},
  author       = {{Eghbali, M and Curmi, J P and Birnir, Bryndis and Gage, P W}},
  issn         = {{0028-0836}},
  language     = {{eng}},
  number       = {{6637}},
  pages        = {{71--75}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature}},
  title        = {{Hippocampal GABA(A) channel conductance increased by diazepam}},
  url          = {{http://dx.doi.org/10.1038/40404}},
  doi          = {{10.1038/40404}},
  volume       = {{388}},
  year         = {{1997}},
}