Gaba Increases Both the Conductance and Mean Open Time of Recombinant Gabaa Channels Co-expressed with Gabarap.
From: Division of Molecular Bioscience, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 0200, Australia.
The Journal of biological chemistry
- Publish Date: Nov 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 47
- Pages: 35699-708
- Medium: Print
- Language: English
- Citation (JAMA): Luu Tien, Gage Peter W, Tierney M Louise, et al. Gaba Increases Both the Conductance and Mean Open Time of Recombinant Gabaa Channels Co-expressed with Gabarap.. J. Biol. Chem. Nov 2006;281:35699-708
Abstract
The single channel properties of recombinant gamma-aminobutyric acid type A (GABA(A))alphabetagamma receptors co-expressed with the trafficking protein GABARAP were investigated using membrane patches in the outside-out patch clamp configuration from transiently transfected L929 cells. In control cells expressing alphabetagamma receptors alone, GABA activated single channels whose main conductance was 30 picosiemens (pS) with a subconductance state of 20 pS, and increasing the GABA concentration did not alter their conductance. In contrast, when GABA(A) receptors were co-expressed with GABARAP, the GABA-activated single channels displayed multiple, high conductances (> or =40 pS), and GABA (> or =10 microM) was able to increase their conductance, up to a maximum of 60 pS. The mean open time of GABA-activated channels in control cells expressing alphabetagamma receptors alone was 2.3 +/- 0.1 ms for the main 30-pS channel and shorter for the subconductance state (20 pS, 0.8 +/- 0.1 ms). Similar values were measured for the 30- and 20-pS channels active in patches from cells co-expressing GABARAP. However higher conductance channels (> or =40 pS) remained open longer, irrespective of whether GABA or GABA plus diazepam activated them. Plotting mean open times against mean conductances revealed a linear relationship between these two parameters. Since high GABA concentrations increase both the maximum single channel conductance and mean open time of GABA(A) channels co-expressed with GABARAP, trafficking processes must influence ion channel properties. This suggests that the organization of extrasynaptic GABA(A) receptors may provide a range of distinct inhibitory currents in the brain and, further, provide differential drug responses.
Mesh Headings (Keywords): Animals, Cell Line, Cytoskeletal Proteins, Diazepam, Dose-Response Relationship, Drug, Electrophysiology, Fibroblasts, GABA Modulators, Ion Channel Gating, Membrane Proteins, Mice, Models, Chemical, Patch-Clamp Techniques, Receptors, GABA-A, Recombinant Proteins, gamma-Aminobutyric Acid
Check for Full Text / PubMed Unique Identifier (PMID): 16954214
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.