ArticleThe Journal of physiology2007
Single-channel study of the spasmodic mutation alpha1A52S in recombinant rat glycine receptors.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
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- Anxiety and Startle Phenotypes inFrontiers in molecular neuroscience · 2020Article
- Applying the Monod-Wyman-Changeux Allosteric Activation Model to Pseudo-Steady-State Responses from GABAMolecular pharmacology · 2019Review
- GABA Type A Receptor Activation in the Allosteric Coagonist Model Framework: Relationship between ECMolecular pharmacology · 2018Article
- The Startle Disease Mutation E103K Impairs Activation of Human Homomeric α1 Glycine Receptors by Disrupting an Intersubunit Salt Bridge across the Agonist Binding Site.The Journal of biological chemistry · 2017Article
- Single-Channel Recording of Ligand-Gated Ion Channels.Cold Spring Harbor protocols · 2016Article
- Murine startle mutant Nmf11 affects the structural stability of the glycine receptor and increases deactivation.The Journal of physiology · 2016Article
- Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses.Pharmacological research · 2015Review
- Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity.British journal of pharmacology · 2015Article
- Control of ethanol sensitivity of the glycine receptor α3 subunit by transmembrane 2, the intracellular splice cassette and C-terminal domains.The Journal of pharmacology and experimental therapeutics · 2015Article
- Don't flip out: AChRs are primed to catch and hold your attention.Biophysical journal · 2014Article
- Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations.Journal of neurophysiology · 2014Article
- The kinetic properties of the α3 rat glycine receptor make it suitable for mediating fast synaptic inhibition.The Journal of physiology · 2013Article
- Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Characterization of two mutations, M287L and Q266I, in the α1 glycine receptor subunit that modify sensitivity to alcohols.The Journal of pharmacology and experimental therapeutics · 2012Article
- The α1K276E startle disease mutation reveals multiple intermediate states in the gating of glycine receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Contributions of conserved residues at the gating interface of glycine receptors.The Journal of biological chemistry · 2011Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Inherited defects in glycine receptors lead to hyperekplexia, or startle disease. A mutant mouse, spasmodic, that has a startle phenotype, has a point mutation (A52S) in the glycine receptor alpha1 subunit. This mutation reduces the sensitivity of the receptor to glycine, but the mechanism by which this occurs is not known. We investigated the properties of A52S recombinant receptors by cell-attached patch-clamp recording of single-channel currents elicited by 30-10000 microM glycine. We used heteromeric receptors, which resemble those found at adult inhibitory synapses. Activation mechanisms were fitted directly to single channel data using the HJCFIT method, which includes an exact correction for missed events. In common with wild-type receptors, only mechanisms with three binding sites and extra shut states could describe the observations. The most physically plausible of these, the 'flip' mechanism, suggests that preopening isomerization to the flipped conformation that follows binding is less favoured in mutant than in wild-type receptors, and, especially, that the flipped conformation has a 100-fold lower affinity for glycine than in wild-type receptors. In contrast, the efficacy of the gating reaction was similar to that of wild-type heteromeric receptors. The reduction in affinity for the flipped conformation accounts for the reduction in apparent cooperativity seen in the mutant receptor (without having to postulate interaction between the binding sites) and it accounts for the increased EC50 for responses to glycine that is seen in mutant receptors. This mechanism also predicts accurately the faster decay of synaptic currents that is observed in spasmodic mice.
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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.