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Penicillin blocks human alpha(1)beta(1) and alpha(1)beta(1)gamma(2S) GABA(A) channels that open spontaneously.

Lindquist, Catarina LU ; Dalziel, Julie E; Cromer, Brett A and Birnir, Bryndis LU (2004) In European Journal of Pharmacology 496(1-3). p.23-32
Abstract
We used the open-channel blocker, penicillin (10 mM), as a tool to investigate if the human α1β1 or α1β1γ2S γ-aminobutyric acid type A (GABAA) receptor channels opened in the absence of GABA. Application of penicillin to cells expressing the receptors resulted in a transient inward whole-cell current, the off-current, upon penicillin removal. The amplitude of the off-current was dependent on the duration of the penicillin application, it reversed in polarity at depolarized potentials and exhibited “run-down” similar to the GABA-activated currents. Bicuculline (100 μM) blocked the off-current response. Pentobarbital (50 μM) enhanced the peak off-current amplitude by 2.8 and 3.4 in α1β1 and α1β1γ2S receptors, respectively. Diazepam (1 μM)... (More)
We used the open-channel blocker, penicillin (10 mM), as a tool to investigate if the human α1β1 or α1β1γ2S γ-aminobutyric acid type A (GABAA) receptor channels opened in the absence of GABA. Application of penicillin to cells expressing the receptors resulted in a transient inward whole-cell current, the off-current, upon penicillin removal. The amplitude of the off-current was dependent on the duration of the penicillin application, it reversed in polarity at depolarized potentials and exhibited “run-down” similar to the GABA-activated currents. Bicuculline (100 μM) blocked the off-current response. Pentobarbital (50 μM) enhanced the peak off-current amplitude by 2.8 and 3.4 in α1β1 and α1β1γ2S receptors, respectively. Diazepam (1 μM) only enhanced the off-current peak response in α1β1γ2S receptors (1.6) and induced the development of an inward current when applied alone. The results are consistent with that the α1β1 or α1β1γ2S GABAA receptors can open in the absence of GABA and raise the question of what role spontaneous channel openings have in the function of GABAA receptors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
γ-aminobutyric acid, Spontaneous activity, Channel block, Tonic current, Inhibition, Barbiturate, Benzodiazepine, GABAA receptor
in
European Journal of Pharmacology
volume
496
issue
1-3
pages
23 - 32
publisher
Elsevier
external identifiers
  • wos:000223307900003
  • pmid:15288571
  • scopus:3543053577
ISSN
1879-0712
DOI
10.1016/j.ejphar.2004.06.004
language
English
LU publication?
yes
id
317a6709-e832-4d55-b0c0-36cd7f143fa5 (old id 126925)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15288571&dopt=Abstract
date added to LUP
2007-07-17 08:00:52
date last changed
2017-12-10 03:40:23
@article{317a6709-e832-4d55-b0c0-36cd7f143fa5,
  abstract     = {We used the open-channel blocker, penicillin (10 mM), as a tool to investigate if the human α1β1 or α1β1γ2S γ-aminobutyric acid type A (GABAA) receptor channels opened in the absence of GABA. Application of penicillin to cells expressing the receptors resulted in a transient inward whole-cell current, the off-current, upon penicillin removal. The amplitude of the off-current was dependent on the duration of the penicillin application, it reversed in polarity at depolarized potentials and exhibited “run-down” similar to the GABA-activated currents. Bicuculline (100 μM) blocked the off-current response. Pentobarbital (50 μM) enhanced the peak off-current amplitude by 2.8 and 3.4 in α1β1 and α1β1γ2S receptors, respectively. Diazepam (1 μM) only enhanced the off-current peak response in α1β1γ2S receptors (1.6) and induced the development of an inward current when applied alone. The results are consistent with that the α1β1 or α1β1γ2S GABAA receptors can open in the absence of GABA and raise the question of what role spontaneous channel openings have in the function of GABAA receptors.},
  author       = {Lindquist, Catarina and Dalziel, Julie E and Cromer, Brett A and Birnir, Bryndis},
  issn         = {1879-0712},
  keyword      = {γ-aminobutyric acid,Spontaneous activity,Channel block,Tonic current,Inhibition,Barbiturate,Benzodiazepine,GABAA receptor},
  language     = {eng},
  number       = {1-3},
  pages        = {23--32},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Penicillin blocks human alpha(1)beta(1) and alpha(1)beta(1)gamma(2S) GABA(A) channels that open spontaneously.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2004.06.004},
  volume       = {496},
  year         = {2004},
}