ArticleThe Journal of physiology2012
A neurosteroid potentiation site can be moved among GABAA receptor subunits.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- A bupropion modulatory site in the Gloeobacter violaceus ligand-gated ion channel.Biophysical journal · 2024Article
- Identification of a binding site for bupropion inbioRxiv : the preprint server for biology · 2023Article
- Pathogenic variants of human GABRA1 gene associated with epilepsy: A computational approach.Heliyon · 2023Article
- Structural insights into opposing actions of neurosteroids on GABANature communications · 2023Article
- Article
- Interfacial binding sites for cholesterol on GABABiophysical journal · 2021Article
- The molecular determinants of neurosteroid binding in the GABA(A) receptor.The Journal of steroid biochemistry and molecular biology · 2019Article
- Structural basis of neurosteroid anesthetic action on GABANature communications · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- Structural basis for GABANature structural & molecular biology · 2017Article
- Crystal structures of a GABANature structural & molecular biology · 2017Article
- A chimeric prokaryotic-eukaryotic pentameric ligand gated ion channel reveals interactions between the extracellular and transmembrane domains shape neurosteroid modulation.Neuropharmacology · 2017Article
- Structural Studies of GABAA Receptor Binding Sites: Which Experimental Structure Tells us What?Frontiers in molecular neuroscience · 2016Article
- Characterization of neurosteroid effects on hyperpolarizing current at α4β2δ GABAA receptors.Psychopharmacology · 2014Article
- Neurosteroid analogues. 18. Structure-activity studies of ent-steroid potentiators of γ-aminobutyric acid type A receptors and comparison of their activities with those of alphaxalone and allopregnanolone.Journal of medicinal chemistry · 2014Article
- Neurosteroids and GABAergic signaling in health and disease.Biomolecular concepts · 2013Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Endogenous neurosteroids are among the most potent and efficacious potentiators of activation of GABA(A) receptors. It has been proposed that a conserved glutamine residue in the first membrane-spanning region (TM1 region) of the α subunits is required for binding of potentiating neurosteroids. Mutations of this residue can reduce or remove the ability of steroids to potentiate function. However, it is not known whether potentiation requires that a steroid interact with the α subunit, or not. To examine this question we mutated the homologous residue in the β2 and γ2L subunits to glutamine, and found that these mutations could not confer potentiation by allopregnanolone (3α5αP) when expressed in receptors containing ineffective α1 subunits. However, potentiation is restored when the entire TM1 region from the α1 subunit is transferred to the β2 or γ2L subunit. Mutations in the TM1 region that affect potentiation when made in the α1 subunit have similar effects when made in transferred TM1 region. Further, the effects of 3α5αP on single-channel kinetics are similar for wild-type receptors and receptors with moved TM1 regions. These results support the idea that steroids bind in the transmembrane regions of the receptor. The observations are consistent with previous work indicating that neurosteroid potentiation is mediated by an action that affects the receptor as a whole, rather than an individual subunit or pair of subunits, and in addition demonstrate that the mechanism is independent of the nature of the subunit that interacts with steroid.
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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.