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Insights into the activation mechanism of ρ 1 GABA receptors obtained by coexpression of wild type and activation-impaired subunits

1996; Royal Society; Volume: 263; Issue: 1368 Linguagem: Inglês

10.1098/rspb.1996.0042

1471-2954

Jahanshah Αmin, David S. Weiss,

Neuroscience and Neuropharmacology Research

Restricted accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Amin Jahanshah and Weiss David S. 1996Insights into the activation mechanism of ρ1 GABA receptors obtained by coexpression of wild type and activation-impaired subunitsProc. R. Soc. Lond. B.263273–282http://doi.org/10.1098/rspb.1996.0042SectionRestricted accessArticleInsights into the activation mechanism of ρ1 GABA receptors obtained by coexpression of wild type and activation-impaired subunits Jahanshah Amin Google Scholar Find this author on PubMed Search for more papers by this author and David S. Weiss Google Scholar Find this author on PubMed Search for more papers by this author Jahanshah Amin Google Scholar Find this author on PubMed and David S. Weiss Google Scholar Find this author on PubMed Published:22 March 1996https://doi.org/10.1098/rspb.1996.0042AbstractTo gain insight into the activation mechanism of homomeric ligand-gated receptor—channels, we examined human homomeric ρ1 GABA receptors with fewer than the normal number of agonist binding sites. This was accomplished by coexpressing different ratios of wild type and activation-impaired ρ1 subunits. Dose—response relations from oocytes coexpressing wild type and mutant subunits were comprised of two components in terms of GABA sensitivity; one 'wild type'-like and the other 'mutant'-like. Applying the binomial hypothesis to subunit coassembly enabled us to correlate these two components of the GABA dose—response relations to the underlying chimaeric receptor subtypes. We demonstrate that the receptors activate near normal provided that they are comprised of at least three wild type subunits. Our data are consistent with five equivalent and independent GABA binding sites of which only three need bind GABA to open the pore. The two additional binding sites may increase the GABA sensitivity of the ρ1 receptor and, when bound by agonist, stabilize the open state.FootnotesThis text was harvested from a scanned image of the original document using optical character recognition (OCR) software. As such, it may contain errors. Please contact the Royal Society if you find an error you would like to see corrected. Mathematical notations produced through Infty OCR. 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Mowrey D, Cheng M, Liu L, Willenbring D, Lu X, Wymore T, Xu Y and Tang P (2013) Asymmetric Ligand Binding Facilitates Conformational Transitions in Pentameric Ligand-Gated Ion Channels, Journal of the American Chemical Society, 10.1021/ja307275v, 135:6, (2172-2180), Online publication date: 13-Feb-2013. Huang S, Lewis T, Lummis S, Thompson A, Chebib M, Johnston G and Duke R (2012) Mixed antagonistic effects of the ginkgolides at recombinant human ρ1 GABAC receptors, Neuropharmacology, 10.1016/j.neuropharm.2012.06.067, 63:6, (1127-1139), Online publication date: 1-Nov-2012. Gussin H, Khasawneh F, Xie A, Feng F, Memic A, Qian H, Le Breton G and Pepperberg D (2011) Subunit-specific polyclonal antibody targeting human ρ1 GABAC receptor, Experimental Eye Research, 10.1016/j.exer.2011.04.009, 93:1, (59-64), Online publication date: 1-Jul-2011. Williams D, Stokes C, Horenstein N and Papke R (2011) The effective opening of nicotinic acetylcholine receptors with single agonist binding sites, Journal of General Physiology, 10.1085/jgp.201010587, 137:4, (369-384), Online publication date: 1-Apr-2011. Xie A, Yan J, Yue L, Feng F, Mir F, Abdel-Halim H, Chebib M, Le Breton G, Standaert R, Qian H and Pepperberg D (2011) 2-Aminoethyl Methylphosphonate, a Potent and Rapidly Acting Antagonist of GABA A -ρ1 Receptors , Molecular Pharmacology, 10.1124/mol.111.071225, 80:6, (965-978), Online publication date: 1-Dec-2011. Miller P and Smart T (2010) Binding, activation and modulation of Cys-loop receptors, Trends in Pharmacological Sciences, 10.1016/j.tips.2009.12.005, 31:4, (161-174), Online publication date: 1-Apr-2010. Chang Y, Wu W, Zhang J and Huang Y (2009) Allosteric activation mechanism of the cys-loop receptors, Acta Pharmacologica Sinica, 10.1038/aps.2009.51, 30:6, (663-672), Online publication date: 1-Jun-2009. Zhang J, Xue F and Chang Y (2009) Agonist- and antagonist-induced conformational changes of loop F and their contributions to the ρ1 GABA receptor function, The Journal of Physiology, 10.1113/jphysiol.2008.160093, 587:1, (139-153), Online publication date: 1-Jan-2009. Khatri A, Sedelnikova A and Weiss D (2009) Structural Rearrangements in Loop F of the GABA Receptor Signal Ligand Binding, Not Channel Activation, Biophysical Journal, 10.1016/j.bpj.2008.09.011, 96:1, (45-55), Online publication date: 1-Jan-2009. Corradi J, Gumilar F and Bouzat C (2009) Single-Channel Kinetic Analysis for Activation and Desensitization of Homomeric 5-HT3A Receptors, Biophysical Journal, 10.1016/j.bpj.2009.06.018, 97:5, (1335-1345), Online publication date: 1-Sep-2009. Bracamontes J and Steinbach J (2008) Multiple Modes for Conferring Surface Expression of Homomeric β1 GABAA Receptors, Journal of Biological Chemistry, 10.1074/jbc.M801292200, 283:38, (26128-26136), Online publication date: 1-Sep-2008. Abdel-Halim H, Hanrahan J, Hibbs D, Johnston G and Chebib M (2008) A Molecular Basis for Agonist and Antagonist Actions at GABA C Receptors , Chemical Biology & Drug Design, 10.1111/j.1747-0285.2008.00642.x, 71:4, (306-327), Online publication date: 1-Apr-2008. Zhang J, Xue F and Chang Y (2008) Structural Determinants for Antagonist Pharmacology That Distinguish the ρ 1 GABA C Receptor from GABA A Receptors , Molecular Pharmacology, 10.1124/mol.108.048710, 74:4, (941-951), Online publication date: 1-Oct-2008. Hadley S and Amin J (2007) Rat α 6 β 2 δ GABA A receptors exhibit two distinct and separable agonist affinities , The Journal of Physiology, 10.1113/jphysiol.2007.132886, 581:3, (1001-1018), Online publication date: 15-Jun-2007. Pan Y, Ripps H and Qian H (2006) Random Assembly of GABA ρ1 and ρ2 Subunits in the Formation of Heteromeric GABA C Receptors, Cellular and Molecular Neurobiology, 10.1007/s10571-006-9001-8, 26:3, (289-305), Online publication date: 1-May-2006. Li W, Covey D, Alakoskela J, Kinnunen P and Steinbach J (2006) Enantiomers of Neuroactive Steroids Support a Specific Interaction with the GABA-C Receptor as the Mechanism of Steroid Action, Molecular Pharmacology, 10.1124/mol.106.022863, 69:6, (1779-1782), Online publication date: 1-Jun-2006. Yang J, Cheng Q, Takahashi A and Goubaeva F (2006) Kinetic Properties of GABA ρ1 Homomeric Receptors Expressed in HEK293 Cells, Biophysical Journal, 10.1529/biophysj.106.085431, 91:6, (2155-2162), Online publication date: 1-Sep-2006. Henchman R, Wang H, Sine S, Taylor P and Andrew McCammon J (2005) Ligand-Induced Conformational Change in the α7 Nicotinic Receptor Ligand Binding Domain, Biophysical Journal, 10.1529/biophysj.104.053934, 88:4, (2564-2576), Online publication date: 1-Apr-2005. 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Carland J, Moore A, Hanrahan J, Mewett K, Duke R, Johnston G and Chebib M (2004) Mutations of the 2′ proline in the M2 domain of the human GABAC ρ1 subunit alter agonist responses, Neuropharmacology, 10.1016/j.neuropharm.2003.11.027, 46:6, (770-781), Online publication date: 1-May-2004. Chang Y and Weiss D (2002) Site-specific fluorescence reveals distinct structural changes with GABA receptor activation and antagonism, Nature Neuroscience, 10.1038/nn926, 5:11, (1163-1168), Online publication date: 1-Nov-2002. Enz R GABAC Receptors: A Molecular View, Biological Chemistry, 10.1515/BC.2001.141, 382:8 Cestari I, Min K, Kulli J and Yang J (2001) Identification of an Amino Acid Defining the Distinct Properties of Murine β1 and β3 Subunit-Containing GABAA Receptors, Journal of Neurochemistry, 10.1046/j.1471-4159.2000.740827.x, 74:2, (827-838) Carlson B, Engblom A, Kristiansen U, Schousboe A and Olsen R (2000) A Single Glycine Residue at the Entrance to the First Membrane-Spanning Domain of the γ-Aminobutyric Acid Type A Receptor β 2 Subunit Affects Allosteric Sensitivity to GABA and Anesthetics , Molecular Pharmacology, 10.1124/mol.57.3.474, 57:3, (474-484), Online publication date: 1-Mar-2000. Chang Y, Covey D and Weiss D (2000) Correlation of the Apparent Affinities and Efficacies of γ-Aminobutyric Acid C Receptor Agonists , Molecular Pharmacology, 10.1124/mol.58.6.1375, 58:6, (1375-1380), Online publication date: 1-Dec-2000. Qian H, Dowling J and Ripps H (1999) A single amino acid in the second transmembrane domain of GABA ? subunits is a determinant of the response kinetics of GABAC receptors, Journal of Neurobiology, 10.1002/(SICI)1097-4695(199907)40:1 3.0.CO;2-4, 40:1, (67-76), Online publication date: 1-Jul-1999. Chang Y and Weiss D (1999) Channel opening locks agonist onto the GABAC receptor, Nature Neuroscience, 10.1038/6313, 2:3, (219-225), Online publication date: 1-Mar-1999. Chang Y and Weiss D (1998) Substitutions of the Highly Conserved M2 Leucine Create Spontaneously Opening ρ1 γ-Aminobutyric Acid Receptors, Molecular Pharmacology, 10.1124/mol.53.3.511, 53:3, (511-523), Online publication date: 1-Mar-1998. Enz R and Cutting G (1998) Molecular composition of GABAC receptors, Vision Research, 10.1016/S0042-6989(97)00277-0, 38:10, (1431-1441), Online publication date: 1-May-1998. Lukasiewicz P and Shields C (1998) Different Combinations of GABA A and GABA C Receptors Confer Distinct Temporal Properties to Retinal Synaptic Responses , Journal of Neurophysiology, 10.1152/jn.1998.79.6.3157, 79:6, (3157-3167), Online publication date: 1-Jun-1998. Koulen P, Brandst�tter J, Kr�ger S, Enz R, Bormann J and W�ssle H (1997) Immunocytochemical localization of the GABAC receptor ? subunits in the cat, goldfish, and chicken retina, The Journal of Comparative Neurology, 10.1002/(SICI)1096-9861(19970421)380:4 3.0.CO;2-3, 380:4, (520-532), Online publication date: 21-Apr-1997. This Issue22 March 1996Volume 263Issue 1368 Article InformationDOI:https://doi.org/10.1098/rspb.1996.0042PubMed:8920250Published by:Royal SocietyPrint ISSN:0962-8452Online ISSN:1471-2954History: Manuscript received03/11/1995Manuscript accepted07/12/1995Published online01/01/1997Published in print22/03/1996 License:Scanned images copyright © 2017, Royal Society Citations and impact Large datasets are available through Proceedings B's partnership with Dryad