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- Birnir, Bryndis, et al.
(författare)
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Conductance of recombinant GABA(A) channels is increased in cells co-expressing GABA(A) receptor-associated protein
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 279:21, s. 21701-21706
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Eghbali, M, et al.
(författare)
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Effects of propofol on GABA(A) channel conductance in rat-cultured hippocampal neurons
- 2003
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 468:2, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- Channels were activated, in ripped-off patches from rat-cultured hippocampal neurons, by propofol alone, propofol plus 0.5 muM GABA (gamma-aminobutyric acid) or GABA alone. The propofol-activated currents were chloride-selective, showed outward-rectification and were enhanced by 1 muM diazepam. The maximum propofol-activated channel conductance increased with propofol concentration from less than 15 pS (10 muM) to about 60 pS (500 muM) but decreased to 40 pS in 1 mM propofol. Fitting the data from 10 to 500 muM propofol with a Hill-type equation gave a maximum conductance of 64 pS, an EC50 value of 32 muM and a Hill coefficient of 1.1. Addition of 0.5 muM GABA shifted the propofol EC50 value to 10 muM and increased the maximum channel conductance to about 100 pS. The Hill coefficient was 0.8. The maximum channel conductance did not increase further when 1 muM diazepam was added together with a saturating propofol concentration and GABA. The results are compared to effects other drugs have on GABA(A) channels conductance. (C) 2003 Elsevier Science B.V All rights reserved.
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