Stoichiometry of a recombinant GABAA receptor.
paper
Cited
Public
Unavailable
- Authors
- Chang, Y; Wang, R; Barot, S; Weiss, D S
- Year
- 1996
- Journal
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- PMID
- 8757254
- DOI
- 10.1523/JNEUROSCI.16-17-05415.1996
- PMCID
- PMC6578878
GABA is the main inhibitory neurotransmitter in the mammalian brain. The postsynaptic GABAA receptor/pore complex is presumed to be a pentamer typically composed of a combination of alpha, beta, and gamma subunits, although the stoichiometry remains controversial. We probed the stoichiometry of the GABAA receptor by site-directed mutagenesis of a conserved leucine (to serine) in the putative second membrane-spanning domain of the rat alpha 1(alpha L263S), beta 2(alpha L259S), and gamma 2(alpha L274S) subunit isoforms. Coexpression of wild-type and mutant subunits of each class (e.g., alpha and alpha L263S), along with their wild-type counter-parts (e.g., beta and gamma), in Xenopus laevis oocytes resulted in mixed populations of receptors with distinct GABA sensitivities. This is consistent with the interpretation that the leucine mutation increased the GABA sensitivity in proportion to the number of incorporated mutant subunits. The apparent number of incorporated subunits for each class (alpha, beta, and gamma) could then be determined from the number of components comprising the compound GABA dose-response relationships. Using this approach, we conclude that the recombinant alpha 1 beta 2 gamma 2 GABAA receptor is a pentamer composed of two alpha subunits, two beta subunits, and one gamma subunit.
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| Title | Year | PMID |
|---|---|---|
| Altering the relative abundance of GABA A receptor subunits changes GABA- and ethanol-responses in Xenopus oocytes. | 2009 | 19382902 |
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| The GABAA receptor gamma2 subunit R43Q mutation linked to childhood absence epilepsy and febrile seizures causes retention of alpha1beta2gamma2S receptors in the endoplasmic reticulum. | Kang JQ et al. | β | 2004 | β |
| Chronic ethanol consumption enhances internalization of alpha1 subunit-containing GABAA receptors in cerebral cortex. | Kumar S et al. | β | 2003 | β |
| Effects of gamma2S subunit incorporation on GABAA receptor macroscopic kinetics. | Boileau AJ et al. | β | 2003 | β |
| GABA(A) alpha1 and alpha2 receptor subunit expression in rostral ventrolateral medulla in nonpregnant and pregnant rats. | Foley CM et al. | β | 2003 | β |
| GABA(Abeta2-3) immunoreactive cells in the developing chick retina. | Barros PH et al. | β | 2003 | β |
| GABA(A) receptor composition is determined by distinct assembly signals within alpha and beta subunits. | Bollan K et al. | β | 2003 | β |
| GABARAP: lessons for synaptogenesis. | Coyle JE et al. | β | 2003 | β |
| Identification of an amino acid sequence within GABA(A) receptor beta3 subunits that is important for receptor assembly. | Ehya N et al. | β | 2003 | β |
| Increased expression of GABA(A) receptor beta-subunits in the hippocampus of patients with temporal lobe epilepsy. | Pirker S et al. | β | 2003 | β |
| Individual properties of the two functional agonist sites in GABA(A) receptors. | Baumann SW et al. | β | 2003 | β |
| Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: the effects on agonist enhancement, direct activation, and inhibition. | Raines DE et al. | β | 2003 | β |
| On high- and low-affinity agonist sites in GABAA receptors. | Baur R et al. | β | 2003 | β |
| Pharmacology of GABA(A) receptors exhibiting different levels of spontaneous activity. | Mortensen M et al. | β | 2003 | β |
| Presynaptic membrane of inhibitory crayfish axon terminals is stained by antibodies raised against mammalian GABA(A) receptor subunits alpha3 and beta(2/3). | Feinstein N et al. | β | 2003 | β |
| Stoichiometry of recombinant heteromeric glycine receptors revealed by a pore-lining region point mutation. | Burzomato V et al. | β | 2003 | β |
| Assembly and cell surface expression of homomeric and heteromeric 5-HT3 receptors: the role of oligomerization and chaperone proteins. | Boyd GW et al. | β | 2002 | β |
| Coupled and uncoupled gating and desensitization effects by pore domain mutations in GABA(A) receptors. | Scheller M et al. | β | 2002 | β |
| Different residues in the GABA(A) receptor alpha 1T60-alpha 1K70 region mediate GABA and SR-95531 actions. | Holden JH et al. | β | 2002 | β |
| Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy. | Palma E et al. | β | 2002 | β |
| Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement. | Baumann SW et al. | β | 2002 | β |
| Functional consequences of the loss of high affinity agonist binding to gamma-aminobutyric acid type A receptors. Implications for receptor desensitization. | Newell JG et al. | β | 2002 | β |
| GABA(A) receptor beta 2 Tyr97 and Leu99 line the GABA-binding site. Insights into mechanisms of agonist and antagonist actions. | Boileau AJ et al. | β | 2002 | β |
| GABA(A) receptor heterogeneity in histaminergic neurons. | Sergeeva OA et al. | β | 2002 | β |
| GABAergic innervation organizes synaptic and extrasynaptic GABAA receptor clustering in cultured hippocampal neurons. | Christie SB et al. | β | 2002 | β |
| Glycine and GABA(A) receptor subunits on Renshaw cells: relationship with presynaptic neurotransmitters and postsynaptic gephyrin clusters. | Geiman EJ et al. | β | 2002 | β |
| Homologous sites of GABA(A) receptor alpha(1), beta(3) and gamma(2) subunits are important for assembly. | Sarto I et al. | β | 2002 | β |
| Molecular structure and physiological function of chloride channels. | Jentsch TJ et al. | β | 2002 | β |
| Overexpression of the GABA(A) receptor epsilon subunit results in insensitivity to anaesthetics. | Thompson SA et al. | β | 2002 | β |
| Pharmacological heterogeneity of gamma-aminobutyric acid receptors during development suggests distinct classes of rat cerebellar granule cells in situ. | Hevers W et al. | β | 2002 | β |
| Prolongation of hippocampal miniature inhibitory postsynaptic currents in mice lacking the GABA(A) receptor alpha1 subunit. | Goldstein PA et al. | β | 2002 | β |
| Role of the histidine residue at position 105 in the human alpha 5 containing GABA(A) receptor on the affinity and efficacy of benzodiazepine site ligands. | Kelly MD et al. | β | 2002 | β |
| Site-specific fluorescence reveals distinct structural changes with GABA receptor activation and antagonism. | Chang Y et al. | β | 2002 | β |
| Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding. | Coyle JE et al. | β | 2002 | β |
| Synaptic and extrasynaptic GABAA receptor and gephyrin clusters. | Christie SB et al. | β | 2002 | β |
| The relative amount of cRNA coding for gamma2 subunits affects stimulation by benzodiazepines in GABA(A) receptors expressed in Xenopus oocytes. | Boileau AJ et al. | β | 2002 | β |
| Tracazolate reveals a novel type of allosteric interaction with recombinant gamma-aminobutyric acid(A) receptors. | Thompson SA et al. | β | 2002 | β |
| Tryptophan scanning mutagenesis in TM4 of the GABA(A) receptor alpha1 subunit: implications for modulation by inhaled anesthetics and ion channel structure. | Jenkins A et al. | β | 2002 | β |
| Two different mechanisms of disinhibition produced by GABAA receptor mutations linked to epilepsy in humans. | Bianchi MT et al. | β | 2002 | β |
| [3H]Ro 15-1788 binding sites to brain membrane of the saltwater Mugil cephalus. | Betti L et al. | β | 2001 | β |
| alpha4beta3delta GABA(A) receptors characterized by fluorescence resonance energy transfer-derived measurements of membrane potential. | Adkins CE et al. | β | 2001 | β |
| Coadministered nitrous oxide enhances the effect of isoflurane on GABAergic transmission by an increase in open-channel block. | Hapfelmeier G et al. | β | 2001 | β |
| Confocal microscopic study of GABA(A) receptors in Xenopus oocytes after rat brain mRNA injection: modulation by tyrosine kinase activity. | Balduzzi R et al. | β | 2001 | β |
| Constructing inhibitory synapses. | Moss SJ et al. | β | 2001 | β |
| Detection and binding properties of GABA(A) receptor assembly intermediates. | Klausberger T et al. | β | 2001 | β |
| Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux. | Smith AJ et al. | β | 2001 | β |
| Effects of GABA(A) receptor partial agonists in primary cultures of cerebellar granule neurons and cerebral cortical neurons reflect different receptor subunit compositions. | Hansen SL et al. | β | 2001 | β |
| Evidence for distinct conformations of the two alpha 1 subunits in diazepam-bound GABA(A) receptors. | Williams DB et al. | β | 2001 | β |
| Evidence for the formation of functionally distinct alphabetagammaepsilon GABA(A) receptors. | Davies PA et al. | β | 2001 | β |
| Formation of functional alpha3beta4alpha5 human neuronal nicotinic receptors in Xenopus oocytes: a reporter mutation approach. | Groot-Kormelink PJ et al. | β | 2001 | β |
| Functional pharmacology of GABA(A) receptors containing the chicken brain gamma 4 subunit. | Forster IC et al. | β | 2001 | β |
| GABAA receptor subunit interactions important for benzodiazepine and zinc modulation: a patch-clamp and single cell RT-PCR study. | Alsbo CW et al. | β | 2001 | β |
| GABA signalling: therapeutic targets for epilepsy, Parkinson's disease and Huntington's disease. | Kleppner SR et al. | β | 2001 | β |
| High affinity central benzodiazepine receptor ligands. Part 2: quantitative structure-activity relationships and comparative molecular field analysis of pyrazolo[4,3-c]quinolin-3-ones. | Savini L et al. | β | 2001 | β |
| Modulation of GABA(A) receptors by benzodiazepines and barbiturates is autonomous of PKC activation. | Ghansah E et al. | β | 2001 | β |
| Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2. | Elster L et al. | β | 2001 | β |
| Mutation of the 9' leucine in the GABA(A) receptor gamma2L subunit produces an apparent decrease in desensitization by stabilizing open states without altering desensitized states. | Bianchi MT et al. | β | 2001 | β |
| Protein mobility and GABA-induced conformational changes in GABA(A) receptor pore-lining M2 segment. | Horenstein J et al. | β | 2001 | β |
| Structural determinants of fast desensitization and desensitization-deactivation coupling in GABAa receptors. | Bianchi MT et al. | β | 2001 | β |
| Subunit arrangement of gamma-aminobutyric acid type A receptors. | Baumann SW et al. | β | 2001 | β |
| Additivities of compounds that increase the numbers of high affinity [3H]muscimol binding sites by different amounts define more than 9 GABA(A) receptor complexes in rat forebrain: implications for schizophrenia and clozapine research. | Squires RF et al. | β | 2000 | β |
| A novel positive allosteric modulator of the GABA(A) receptor: the action of (+)-ROD188. | Thomet U et al. | β | 2000 | β |
| Arg-274 and Leu-277 of the gamma-aminobutyric acid type A receptor alpha 2 subunit define agonist efficacy and potency. | O'Shea SM et al. | β | 2000 | β |
| A single amino acid residue on the alpha(5) subunit (Ile215) is essential for ligand selectivity at alpha(5)beta(3)gamma(2) gamma-aminobutyric acid(A) receptors. | Strakhova MI et al. | β | 2000 | β |
| A single glycine residue at the entrance to the first membrane-spanning domain of the gamma-aminobutyric acid type A receptor beta(2) subunit affects allosteric sensitivity to GABA and anesthetics. | Carlson BX et al. | β | 2000 | β |
| Benzodiazepines induce a conformational change in the region of the gamma-aminobutyric acid type A receptor alpha(1)-subunit M3 membrane-spanning segment. | Williams DB et al. | β | 2000 | β |
| Developmental switch in the expression of GABA(A) receptor subunits alpha(1) and alpha(2) in the hypothalamus and limbic system of the rat. | Davis AM et al. | β | 2000 | β |
| Electrophysiological evidence for the coexistence of alpha1 and alpha6 subunits in a single functional GABA(A) receptor. | Sigel E et al. | β | 2000 | β |
| GABA(A) receptor assembly. Identification and structure of gamma(2) sequences forming the intersubunit contacts with alpha(1) and beta(3) subunits. | Klausberger T et al. | β | 2000 | β |
| Identification of an amino acid defining the distinct properties of murine beta1 and beta3 subunit-containing GABA(A) receptors. | Cestari IN et al. | β | 2000 | β |
| Influence of subunit configuration on the interaction of picrotoxin-site ligands with recombinant GABA(A) receptors. | Bell-Horner CL et al. | β | 2000 | β |
| Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABA(A) receptors. | Hapfelmeier G et al. | β | 2000 | β |
| Protracted postnatal development of inhibitory synaptic transmission in rat hippocampal area CA1 neurons. | Cohen AS et al. | β | 2000 | β |
| Role of bicarbonate ion in mediating decreased synaptic conductance in benzodiazepine tolerant hippocampal CA1 pyramidal neurons. | Zeng XJ et al. | β | 2000 | β |
| Role of the GABA(A)beta2, GABA(A)alpha6, GABA(A)alpha1 and GABA(A)gamma2 receptor subunit genes cluster in drug responses and the development of alcohol dependence. | Loh EW et al. | β | 2000 | β |
| Stable GABA(A) receptor intermediates in SF-9 cells expressing alpha1, beta2 and gamma2 subunits. | Elster L et al. | β | 2000 | β |
| Stoichiometry of human recombinant neuronal nicotinic receptors containing the b3 subunit expressed in Xenopus oocytes. | Boorman JP et al. | β | 2000 | β |
| The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. | Krasowski MD et al. | β | 2000 | β |
| Tryptophan scanning mutagenesis in TM2 of the GABA(A) receptor alpha subunit: effects on channel gating and regulation by ethanol. | Ueno S et al. | β | 2000 | β |
| Two conserved arginines in the extracellular N-terminal domain of the GABA(A) receptor alpha(5) subunit are crucial for receptor function. | Hartvig L et al. | β | 2000 | β |
| Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands. | Rinaldi D et al. | β | 2000 | β |
| Tyrosine 62 of the gamma-aminobutyric acid type A receptor beta 2 subunit is an important determinant of high affinity agonist binding. | Newell JG et al. | β | 2000 | β |
| Actions of fluorinated alkanols on GABA(A) receptors: relevance to theories of narcosis. | Ueno S et al. | β | 1999 | β |
| Agonist gating and isoflurane potentiation in the human gamma-aminobutyric acid type A receptor determined by the volume of a second transmembrane domain residue. | Koltchine VV et al. | β | 1999 | β |
| Allosteric activation mechanism of the alpha 1 beta 2 gamma 2 gamma-aminobutyric acid type A receptor revealed by mutation of the conserved M2 leucine. | Chang Y et al. | β | 1999 | β |
| An electrogenic ionic pump derived from an ionotropic receptor: assessment of a candidate. | Rapallino MV et al. | β | 1999 | β |
| An update on GABAA receptors. | Mehta AK et al. | β | 1999 | β |
| Biphasic modulation of GABA(A) receptor binding by steroids suggests functional correlates. | Srinivasan S et al. | β | 1999 | β |
| Channel opening locks agonist onto the GABAC receptor. | Chang Y et al. | β | 1999 | β |
| Dual mode of stimulation by the beta-carboline ZK 91085 of recombinant GABA(A) receptor currents: molecular determinants affecting its action. | Thomet U et al. | β | 1999 | β |
| GABA(A) receptors expressed in undifferentiated human teratocarcinoma NT2 cells differ from those expressed by differentiated NT2-N cells. | Neelands TR et al. | β | 1999 | β |
| Gamma-aminobutyric acid increases the water accessibility of M3 membrane-spanning segment residues in gamma-aminobutyric acid type A receptors. | Williams DB et al. | β | 1999 | β |
| General anaesthetic actions on ligand-gated ion channels. | Krasowski MD et al. | β | 1999 | β |
| Incorporation of the pi subunit into functional gamma-aminobutyric Acid(A) receptors. | Neelands TR et al. | β | 1999 | β |
| Modulation of synaptic GABAA receptor function by PKA and PKC in adult hippocampal neurons. | Poisbeau P et al. | β | 1999 | β |
| Molecular and functional diversity of the expanding GABA-A receptor gene family. | Whiting PJ et al. | β | 1999 | β |
| Mutation at the putative GABA(A) ion-channel gate reveals changes in allosteric modulation. | Thompson SA et al. | β | 1999 | β |
| Normal electrophysiological and behavioral responses to ethanol in mice lacking the long splice variant of the gamma2 subunit of the gamma-aminobutyrate type A receptor. | Homanics GE et al. | β | 1999 | β |
| Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus. | Sur C et al. | β | 1999 | β |
| Presynaptic ionotropic receptors and the control of transmitter release. | MacDermott AB et al. | β | 1999 | β |
| Receptor system response kinetics reveal functional subtypes of native murine and recombinant human GABAA receptors. | McClellan AM et al. | β | 1999 | β |
| Stoichiometry of a ligand-gated ion channel determined by fluorescence energy transfer. | Farrar SJ et al. | β | 1999 | β |
| Structure and subunit composition of GABA(A) receptors. | Sieghart W et al. | β | 1999 | β |
| Subunit mutations affect ethanol actions on GABA(A) receptors expressed in Xenopus oocytes. | Ueno S et al. | β | 1999 | β |
| Temporal and regional regulation of alpha1, beta2 and beta3, but not alpha2, alpha4, alpha5, alpha6, beta1 or gamma2 GABA(A) receptor subunit messenger RNAs following one-week oral flurazepam administration. | Tietz EI et al. | β | 1999 | β |
| The effects of a point mutation of the beta2 subunit of GABA(A) receptor on direct and modulatory actions of general anesthetics. | Fukami S et al. | β | 1999 | β |
| The GABA-A receptor gene family: new targets for therapeutic intervention. | Whiting PJ | β | 1999 | β |
| theta, a novel gamma-aminobutyric acid type A receptor subunit. | Bonnert TP et al. | β | 1999 | β |
| A GABAA receptor alpha1 subunit tagged with green fluorescent protein requires a beta subunit for functional surface expression. | Connor JX et al. | β | 1998 | β |
| Allosteric receptors after 30 years. | Changeux JP et al. | β | 1998 | β |
| Allosteric transitions of the acetylcholine receptor. | Edelstein SJ et al. | β | 1998 | β |
| Anomalous rectifying properties of 'diazepam-insensitive' GABA(A) receptors. | Granja R et al. | β | 1998 | β |
| A reporter mutation approach shows incorporation of the "orphan" subunit beta3 into a functional nicotinic receptor. | Groot-Kormelink PJ et al. | β | 1998 | β |
| Expression of alpha3, beta3 and gamma1 GABA(A) receptor subunit messenger RNAs in visual cortex and lateral geniculate nucleus of normal and monocularly deprived monkeys. | Huntsman MM et al. | β | 1998 | β |
| From GABAA receptor diversity emerges a unified vision of GABAergic inhibition. | Costa E | β | 1998 | β |
| GABA(A) receptor function in epileptic human dentate granule cells: comparison to epileptic and control rat. | Shumate MD et al. | β | 1998 | β |
| GABA-gated Cl- channels in the rat retina. | Feigenspan A et al. | β | 1998 | β |
| Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo. | Fritschy JM et al. | β | 1998 | β |
| Pharmacological and functional implications of developmentally-regulated changes in GABA(A) receptor subunit expression in the cerebellum. | Carlson BX et al. | β | 1998 | β |
| Photoaffinity labeling of the benzodiazepine binding site of alpha1beta3gamma2 gamma-aminobutyric acidA receptors with flunitrazepam identifies a subset of ligands that interact directly with His102 of the alpha subunit and predicts orientation of these within the benzodiazepine pharmacophore. | McKernan RM et al. | β | 1998 | β |
| Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane. | Krasowski MD et al. | β | 1998 | β |
| Substitutions of the highly conserved M2 leucine create spontaneously opening rho1 gamma-aminobutyric acid receptors. | Chang Y et al. | β | 1998 | β |
| Subunit composition and quantitative importance of hetero-oligomeric receptors: GABAA receptors containing alpha6 subunits. | Jechlinger M et al. | β | 1998 | β |
| The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes. | Hevers W et al. | β | 1998 | β |
| The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor. | McGurk KA et al. | β | 1998 | β |
| Zinc and zolpidem modulate mIPSCs in rat neocortical pyramidal neurons. | Defazio T et al. | β | 1998 | β |
| Activation and deactivation rates of recombinant GABA(A) receptor channels are dependent on alpha-subunit isoform. | Lavoie AM et al. | β | 1997 | β |
| Antiepileptic drug cellular mechanisms of action: where does lamotrigine fit in? | Coulter DA | β | 1997 | β |
| Assembly of GABAA receptors composed of alpha1 and beta2 subunits in both cultured neurons and fibroblasts. | Gorrie GH et al. | β | 1997 | β |
| avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. | Dent JA et al. | β | 1997 | β |
| Coexistence of two beta subunit isoforms in the same gamma-aminobutyric acid type A receptor. | Li M et al. | β | 1997 | β |
| Diazepam enhancement of GABA-gated currents in binary and ternary GABAA receptors: relationship to benzodiazepine binding site density. | Granja R et al. | β | 1997 | β |
| Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude. | Nusser Z et al. | β | 1997 | β |
| Expression of GABA(A) receptor subunit mRNAs by layer V pyramidal cells of the rat primary visual cortex. | Ruano D et al. | β | 1997 | β |
| Functional properties of recombinant GABA(A) receptors composed of single or multiple beta subunit subtypes. | Fisher JL et al. | β | 1997 | β |
| Key amino acids in the gamma subunit of the gamma-aminobutyric acidA receptor that determine ligand binding and modulation at the benzodiazepine site. | Wingrove PB et al. | β | 1997 | β |
| Myasthenic nicotinic receptor mutant interpreted in terms of the allosteric model. | Edelstein SJ et al. | β | 1997 | β |
| Neuronal nicotinic threonine-for-leucine 247 alpha7 mutant receptors show different gating kinetics when activated by acetylcholine or by the noncompetitive agonist 5-hydroxytryptamine. | Palma E et al. | β | 1997 | β |
| Stoichiometry and assembly of a recombinant GABAA receptor subtype. | Tretter V et al. | β | 1997 | β |
| Stoichiometry of recombinant N-methyl-D-aspartate receptor channels inferred from single-channel current patterns. | Premkumar LS et al. | β | 1997 | β |