ArticleMolecular pharmacology2014
γ-aminobutyric acid type A α4, β2, and δ subunits assemble to produce more than one functionally distinct receptor type.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Introducing a proline in the α1 M2-M3 linker relieves a molecular brake on channel activation in α1β2γ2 GABAA receptors.PloS one · 2026Article
- GABAiScience · 2025Article
- Structural insights into opposing actions of neurosteroids on GABANature communications · 2023Article
- The fate of interneurons, GABABrain pathology (Zurich, Switzerland) · 2023Review
- Differential assembly diversifies GABANature · 2022Article
- Structural determinants and regulation of spontaneous activity in GABANature communications · 2021Article
- Pharmacological and Biophysical Characteristics of Picrotoxin-Resistant, δSubunit-Containing GABAFrontiers in synaptic neuroscience · 2021Article
- Flumazenil-Insensitive Benzodiazepine Effects in Recombinant αβ and Neuronal GABABrain sciences · 2020Article
- A novel de novo variant of GABRA1 causes increased sensitivity for GABA in vitro.Scientific reports · 2020Article
- Steady-state activation of the high-affinity isoform of the α4β2δ GABAScientific reports · 2019Article
- Steady-state activation and modulation of the synaptic-type α1β2γ2L GABAPhysiological reports · 2019Article
- Multiple functional neurosteroid binding sites on GABAA receptors.PLoS biology · 2019Article
- Chemogenetic Isolation Reveals Synaptic Contribution of δ GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- GABA beyond the synapse: defining the subtype-specific pharmacodynamics of non-synaptic GABAThe Journal of physiology · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
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- General Anesthetic Binding Sites in Human α4β3δ γ-Aminobutyric Acid Type A Receptors (GABAARs).The Journal of biological chemistry · 2016Article
- Immunochemical Localization of GABANeurochemical research · 2016Article
- Comparison of γ-Aminobutyric Acid, Type A (GABAA), Receptor αβγ and αβδ Expression Using Flow Cytometry and Electrophysiology: EVIDENCE FOR ALTERNATIVE SUBUNIT STOICHIOMETRIES AND ARRANGEMENTS.The Journal of biological chemistry · 2016Article
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Authors and funding
7 authors at 1 institution.
Funding
Abstract
Native γ-aminobutyric acid (GABA)A receptors consisting of α4, β1-3, and δ subunits mediate responses to the low, tonic concentration of GABA present in the extracellular milieu. Previous studies on heterologously expressed α4βδ receptors have shown a large degree of variability in functional properties, including sensitivity to the transmitter. We studied properties of α4β2δ receptors employing free subunits and concatemeric constructs, expressed in Xenopus oocytes, HEK 293 cells, and cultured hippocampal neurons. The expression system had a strong effect on the properties of receptors containing free subunits. The midpoint of GABA activation curve was 10 nM for receptors in oocytes versus 2300 nM in HEK cells. Receptors activated by the steroid alfaxalone had an estimated maximal open probability of 0.6 in oocytes and 0.01 in HEK cells. Irrespective of the expression system, receptors resulting from combining the tandem construct β2-δ and a free α4 subunit exhibited large steroid responses. We propose that free α4, β2, and δ subunits assemble in different configurations with distinct properties in oocytes and HEK cells, and that subunit linkage can overcome the expression system-dependent preferential assembly of free subunits. Hippocampal neurons transfected with α4 and the picrotoxin-resistant δ(T269Y) subunit showed large responses to alfaxalone in the presence of picrotoxin, suggesting that α4βδ receptors may assemble in a similar configuration in neurons and oocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.