Advanced

Conductance of recombinant GABA(A) channels is increased in cells co-expressing GABA(A) receptor-associated protein

Everitt, AB; Luu, T; Cromer, B; Tierney, ML; Birnir, Bryndis LU ; Olsen, RW and Gage, PW (2004) In Journal of Biological Chemistry 279(21). p.21701-21706
Abstract
High conductance gamma- aminobutyric acid type A ( GABA(A)) channels (> 40 picosiemens ( pS)) have been reported in some studies on GABA(A) channels in situ but not in others, whereas recombinant GABA(A) channels do not appear to display conductances above 40 pS. Furthermore, the conductance of some native GABA(A) channels can be increased by diazepam or pentobarbital, which are effects not reported for expressed GABA(A) channels. GABARAP, a protein associated with native GABA(A) channels, has been reported to cause clustering of GABA(A) receptors and changes in channel kinetics. We have recorded single channel currents activated by GABA in L929 cells expressing alpha(1), beta(1), and gamma(2S) subunits of human GABA(A) receptors.... (More)
High conductance gamma- aminobutyric acid type A ( GABA(A)) channels (> 40 picosiemens ( pS)) have been reported in some studies on GABA(A) channels in situ but not in others, whereas recombinant GABA(A) channels do not appear to display conductances above 40 pS. Furthermore, the conductance of some native GABA(A) channels can be increased by diazepam or pentobarbital, which are effects not reported for expressed GABA(A) channels. GABARAP, a protein associated with native GABA(A) channels, has been reported to cause clustering of GABA(A) receptors and changes in channel kinetics. We have recorded single channel currents activated by GABA in L929 cells expressing alpha(1), beta(1), and gamma(2S) subunits of human GABA(A) receptors. Channel conductance was never higher than 40 pS and was not significantly increased by diazepam or pentobarbital, although open probability was increased. In contrast, in cells expressing the same three subunits together with GABARAP, channel conductance could be significantly higher than 40 pS, and channel conductance was increased by diazepam and pentobarbital. GABARAP caused clustering of receptors in L929 cells, and we suggest that there may be interactions between subunits of clustered GABA(A) receptors that make them open co- operatively to give high conductance " channels." Recombinant channels may require the influence of GABARAP and perhaps other intracellular proteins to adopt a fuller repertoire of properties of native channels. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
21
pages
21701 - 21706
publisher
ASBMB
external identifiers
  • wos:000221417100004
  • scopus:2542463899
ISSN
1083-351X
DOI
10.1074/jbc.M312806200
language
English
LU publication?
yes
id
b7f1e6c7-f505-4877-a8e2-6d8de8c6694b (old id 277915)
date added to LUP
2007-10-22 15:13:13
date last changed
2017-05-28 03:28:34
@article{b7f1e6c7-f505-4877-a8e2-6d8de8c6694b,
  abstract     = {High conductance gamma- aminobutyric acid type A ( GABA(A)) channels (> 40 picosiemens ( pS)) have been reported in some studies on GABA(A) channels in situ but not in others, whereas recombinant GABA(A) channels do not appear to display conductances above 40 pS. Furthermore, the conductance of some native GABA(A) channels can be increased by diazepam or pentobarbital, which are effects not reported for expressed GABA(A) channels. GABARAP, a protein associated with native GABA(A) channels, has been reported to cause clustering of GABA(A) receptors and changes in channel kinetics. We have recorded single channel currents activated by GABA in L929 cells expressing alpha(1), beta(1), and gamma(2S) subunits of human GABA(A) receptors. Channel conductance was never higher than 40 pS and was not significantly increased by diazepam or pentobarbital, although open probability was increased. In contrast, in cells expressing the same three subunits together with GABARAP, channel conductance could be significantly higher than 40 pS, and channel conductance was increased by diazepam and pentobarbital. GABARAP caused clustering of receptors in L929 cells, and we suggest that there may be interactions between subunits of clustered GABA(A) receptors that make them open co- operatively to give high conductance " channels." Recombinant channels may require the influence of GABARAP and perhaps other intracellular proteins to adopt a fuller repertoire of properties of native channels.},
  author       = {Everitt, AB and Luu, T and Cromer, B and Tierney, ML and Birnir, Bryndis and Olsen, RW and Gage, PW},
  issn         = {1083-351X},
  language     = {eng},
  number       = {21},
  pages        = {21701--21706},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Conductance of recombinant GABA(A) channels is increased in cells co-expressing GABA(A) receptor-associated protein},
  url          = {http://dx.doi.org/10.1074/jbc.M312806200},
  volume       = {279},
  year         = {2004},
}