ArticleThe European journal of neuroscience2007
Desensitization and binding properties determine distinct alpha1beta2gamma2 and alpha3beta2gamma2 GABA(A) receptor-channel kinetic behavior.
Article in The European journal of neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
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- Inhibition, but not excitation, recovers from partial cone loss with greater spatiotemporal integration, synapse density, and frequency.Cell reports · 2022Article
- Stereological estimations and neurochemical characterization of neurons expressing GABAA and GABAB receptors in the rat pedunculopontine and laterodorsal tegmental nuclei.Brain structure & function · 2022Article
- Transient expression of a GABA receptor subunit during early development is critical for inhibitory synapse maturation and function.Current biology : CB · 2021Article
- Factors of sex and age dictate the regulation of GABAergic activity by corticotropin-releasing factor receptor 1 in the medial sub-nucleus of the central amygdala.Neuropharmacology · 2021Article
- Comparison of biophysical properties of α1β2 and α3β2 GABAA receptors in whole-cell patch-clamp electrophysiological recordings.PloS one · 2020Article
- Steady-State Activation and Modulation of the ConcatemericMolecular pharmacology · 2019Article
- GABAFrontiers in systems neuroscience · 2019Article
- Major Contribution of Somatostatin-Expressing Interneurons and Cannabinoid Receptors to Increased GABA Synaptic Activity in the Striatum of Huntington's Disease Mice.Frontiers in synaptic neuroscience · 2019Article
- Persistent Sodium Current Drives Excitability of Immature Renshaw Cells in Early Embryonic Spinal Networks.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Spatiotemporal Distribution of GABAFrontiers in neuroanatomy · 2018Article
- Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly Efficient CRISPR/Cas9-Mediated Gene Editing.Molecular therapy. Methods & clinical development · 2017Article
- Synaptic GABAA receptor clustering without the γ2 subunit.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome.The Journal of biological chemistry · 2013Article
- Shift from phasic to tonic GABAergic transmission following laser-lesions in the rat visual cortex.Pflugers Archiv : European journal of physiology · 2013Article
- Tonic inhibition in principal cells of the amygdala: a central role for α3 subunit-containing GABAA receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
GABA(A) receptor subtypes comprising the alpha1 and alpha3 subunits change with development and have a specific anatomical localization in the adult brain. These receptor subtypes have been previously demonstrated to greatly differ in deactivation kinetics but the underlying gating mechanisms have not been fully elucidated. Therefore, we expressed rat alpha1beta2gamma2 and alpha3beta2gamma2 receptors in human embryonic kidney 293 cells and recorded current responses to ultrafast GABA applications at macroscopic and single-channel levels. We found that the slow deactivation of alpha3beta2gamma2-mediated currents is associated with a relatively small rate and extent of apparent desensitization. In contrast, responses mediated by alpha1beta2gamma2 receptors had faster deactivation and stronger desensitization. Alpha3beta2gamma2 receptors had faster recovery in the paired-pulse agonist applications than alpha1beta2gamma2 channels. The onset of currents mediated by alpha3beta2gamma2 receptors was slower than that of alpha1beta2gamma2 for a wide range of GABA concentrations. Single-channel analysis did not reveal differences in the opening/closing kinetics of alpha1beta2gamma2 and alpha3beta2gamma2 channels but burst durations were longer in alpha3beta2gamma2 receptors. Simulation with a previously reported kinetic model was used to explore the differences in respective rate constants. Reproduction of major kinetic differences required a smaller desensitization rate as well as smaller binding and unbinding rates in alpha3beta2gamma2 compared with alpha1beta2gamma2 receptors. Our work describes the mechanisms underlying the kinetic differences between two major GABA(A) receptor subtypes and provides a framework to interpret data from native GABA receptors.
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