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Pentobarbital modulates gamma-aminobutyric acid-activated single-channel conductance in rat cultured hippocampal neurons

Eghbali, M; Gage, P W and Birnir, Bryndis LU (2000) In Molecular Pharmacology 58(3). p.463-469
Abstract
We examined the effect of a range of pentobarbital concentrations on 0.5 microM gamma-aminobutyric acid (GABA)-activated channels (10 +/- 1 pS) in inside-out or outside-out patches from rat cultured hippocampal neurons. The conductance increased from 12 +/- 4 to 62 +/- 9 pS as the pentobarbital concentration was raised from 10 to 500 microM and the data could be fitted by a Hill-type equation. At 100 microM pentobarbital plus 0.5 microM GABA, the conductance seemed to reach a plateau. The pentobarbital EC(50)(0.5 microM GABA) value was 22 +/- 4 microM and n was 1.9 +/- 0.5. In 1 mM pentobarbital plus 0.5 microM GABA, the single-channel conductance decreased to 34 +/- 8 pS. This apparent inhibition of channel conductance was relieved by 1... (More)
We examined the effect of a range of pentobarbital concentrations on 0.5 microM gamma-aminobutyric acid (GABA)-activated channels (10 +/- 1 pS) in inside-out or outside-out patches from rat cultured hippocampal neurons. The conductance increased from 12 +/- 4 to 62 +/- 9 pS as the pentobarbital concentration was raised from 10 to 500 microM and the data could be fitted by a Hill-type equation. At 100 microM pentobarbital plus 0.5 microM GABA, the conductance seemed to reach a plateau. The pentobarbital EC(50)(0.5 microM GABA) value was 22 +/- 4 microM and n was 1.9 +/- 0.5. In 1 mM pentobarbital plus 0.5 microM GABA, the single-channel conductance decreased to 34 +/- 8 pS. This apparent inhibition of channel conductance was relieved by 1 microM diazepam. The channel conductance was 64 +/- 6 pS in the presence of all three drugs. The channels were open more in the presence of both GABA and pentobarbital than in the presence of either drug alone. Pentobarbital alone (100 microM) activated channels with conductance (30 +/- 2 pS) and kinetic properties distinct from those activated by either GABA alone or GABA plus pentobarbital. Whether pentobarbital induces new conformations or promotes conformations observed in the presence of GABA alone cannot be determined from our study, but the results clearly show that it is the combination of drugs present that determines the single-channel conductance and the kinetic properties of the receptors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Pharmacology
volume
58
issue
3
pages
463 - 469
publisher
American Society for Pharmacology and Experimental Therapeutics
external identifiers
  • pmid:10953037
  • scopus:0033857637
ISSN
1521-0111
language
English
LU publication?
yes
id
c4691f57-da16-4e8e-9281-0c4ddfd250ab (old id 1117273)
alternative location
http://molpharm.aspetjournals.org/cgi/content/full/58/3/463
date added to LUP
2008-07-01 08:29:15
date last changed
2017-01-01 04:50:36
@article{c4691f57-da16-4e8e-9281-0c4ddfd250ab,
  abstract     = {We examined the effect of a range of pentobarbital concentrations on 0.5 microM gamma-aminobutyric acid (GABA)-activated channels (10 +/- 1 pS) in inside-out or outside-out patches from rat cultured hippocampal neurons. The conductance increased from 12 +/- 4 to 62 +/- 9 pS as the pentobarbital concentration was raised from 10 to 500 microM and the data could be fitted by a Hill-type equation. At 100 microM pentobarbital plus 0.5 microM GABA, the conductance seemed to reach a plateau. The pentobarbital EC(50)(0.5 microM GABA) value was 22 +/- 4 microM and n was 1.9 +/- 0.5. In 1 mM pentobarbital plus 0.5 microM GABA, the single-channel conductance decreased to 34 +/- 8 pS. This apparent inhibition of channel conductance was relieved by 1 microM diazepam. The channel conductance was 64 +/- 6 pS in the presence of all three drugs. The channels were open more in the presence of both GABA and pentobarbital than in the presence of either drug alone. Pentobarbital alone (100 microM) activated channels with conductance (30 +/- 2 pS) and kinetic properties distinct from those activated by either GABA alone or GABA plus pentobarbital. Whether pentobarbital induces new conformations or promotes conformations observed in the presence of GABA alone cannot be determined from our study, but the results clearly show that it is the combination of drugs present that determines the single-channel conductance and the kinetic properties of the receptors.},
  author       = {Eghbali, M and Gage, P W and Birnir, Bryndis},
  issn         = {1521-0111},
  language     = {eng},
  number       = {3},
  pages        = {463--469},
  publisher    = {American Society for Pharmacology and Experimental Therapeutics},
  series       = {Molecular Pharmacology},
  title        = {Pentobarbital modulates gamma-aminobutyric acid-activated single-channel conductance in rat cultured hippocampal neurons},
  volume       = {58},
  year         = {2000},
}