A role for the 2′ residue in the second transmembrane helix of the GABAA receptor γ2S subunit in channel conductance and gating

Luu, T., Cromer, B., Gage, P. W. and Tierney, M. L. (2005) A role for the 2′ residue in the second transmembrane helix of the GABAA receptor γ2S subunit in channel conductance and gating. Journal of Membrane Biology, 205 1: 17-28. doi:10.1007/s00232-005-0759-2


Author Luu, T.
Cromer, B.
Gage, P. W.
Tierney, M. L.
Title A role for the 2′ residue in the second transmembrane helix of the GABAA receptor γ2S subunit in channel conductance and gating
Journal name Journal of Membrane Biology   Check publisher's open access policy
ISSN 0022-2631
1432-1424
Publication date 2005-05
Year available 2006
Sub-type Article (original research)
DOI 10.1007/s00232-005-0759-2
Volume 205
Issue 1
Start page 17
End page 28
Total pages 12
Place of publication New York, USA
Publisher Springer
Language eng
Subject 11 Medical and Health Sciences
1109 Neurosciences
Abstract GABAA receptors composed of a, b and c subunits display a significantly higher single-channel conductance than receptors comprised of only a and b subunits. The pore of GABAA receptors is lined by the second transmembrane region from each of its five subunits and includes conserved threonines at the 6¢, 10¢ and 13¢ positions. At the 2¢ position, however, a polar residue is present in the c subunit but not the a or b subunits. As residues at the 2¢, 6¢ and 10¢ positions are exposed in the open channel and as such polar channel-lining residues may interact with permeant ions by substituting for water interactions, we compared both the single-channel conductance and the kinetic properties of wild-type a1b1 and a1b1c2S receptors with two mutant receptors, abc(S2¢A) and abc(S2¢V). We found that the single-channel conductance of both mutant abc receptors was significantly decreased with respect to wild-type abc, with the presence of the larger valine side chain having the greatest effect. However, the conductance of the mutant abc receptors remained larger than wild-type ab channels. This reduction in the conductance of mutant abc receptors was observed at depolarized potentials only (ECl = )1.8 mV), which revealed an asymmetry in the ion conduction pathway mediated by the c2¢ residue. The substitutions at the c2¢ serine residue also altered the gating properties of the channel in addition to the effects on the conductance with the open probability of the mutant channels being decreased while the mean open time increased. The data presented in this study show that residues at the 2¢ position in M2 of the c subunit affects both single-channel conductance and receptor kinetics.
Keyword GABA
Single-channel
Conductance
Gating
Kinetics
Gamma subunit
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 23 Dec 2009, 16:00:38 EST by Macushla Boyle on behalf of Queensland Brain Institute