Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses

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208 Citations (Scopus)

Abstract

Neural inhibition in the brain is mainly mediated by ionotropic γ-aminobutyric acid type A (GABAA) receptors. Different subtypes of these receptors, distinguished by their subunit composition, are either concentrated at postsynaptic sites where they mediate phasic inhibition or found at perisynaptic and extrasynaptic locations where they prolong phasic inhibition and mediate tonic inhibition, respectively. Of special interest are mechanisms that modulate the stability and function of postsynaptic GABA A receptor subtypes and that are implicated in functional plasticity of inhibitory transmission in the brain. We will summarize recent progress on the classification of synaptic versus extrasynaptic receptors, the molecular composition of the postsynaptic cytoskeleton, the function of receptor-associated proteins in trafficking of GABAA receptors to and from synapses, and their role in post-translational signaling mechanisms that modulate the stability, density, and function of GABAA receptors in the postsynaptic membrane.

Original languageEnglish (US)
Pages (from-to)195-221
Number of pages27
JournalPharmacology and Therapeutics
Volume102
Issue number3
DOIs
StatePublished - Jun 1 2004

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GABA-A Receptors
Synapses
Neural Inhibition
Aminobutyrates
Brain
Protein Transport
Cytoskeleton
Membranes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

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title = "Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses",
abstract = "Neural inhibition in the brain is mainly mediated by ionotropic γ-aminobutyric acid type A (GABAA) receptors. Different subtypes of these receptors, distinguished by their subunit composition, are either concentrated at postsynaptic sites where they mediate phasic inhibition or found at perisynaptic and extrasynaptic locations where they prolong phasic inhibition and mediate tonic inhibition, respectively. Of special interest are mechanisms that modulate the stability and function of postsynaptic GABA A receptor subtypes and that are implicated in functional plasticity of inhibitory transmission in the brain. We will summarize recent progress on the classification of synaptic versus extrasynaptic receptors, the molecular composition of the postsynaptic cytoskeleton, the function of receptor-associated proteins in trafficking of GABAA receptors to and from synapses, and their role in post-translational signaling mechanisms that modulate the stability, density, and function of GABAA receptors in the postsynaptic membrane.",
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T1 - Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses

AU - Luscher, Bernhard

AU - Keller Capone, Cheryl A.

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N2 - Neural inhibition in the brain is mainly mediated by ionotropic γ-aminobutyric acid type A (GABAA) receptors. Different subtypes of these receptors, distinguished by their subunit composition, are either concentrated at postsynaptic sites where they mediate phasic inhibition or found at perisynaptic and extrasynaptic locations where they prolong phasic inhibition and mediate tonic inhibition, respectively. Of special interest are mechanisms that modulate the stability and function of postsynaptic GABA A receptor subtypes and that are implicated in functional plasticity of inhibitory transmission in the brain. We will summarize recent progress on the classification of synaptic versus extrasynaptic receptors, the molecular composition of the postsynaptic cytoskeleton, the function of receptor-associated proteins in trafficking of GABAA receptors to and from synapses, and their role in post-translational signaling mechanisms that modulate the stability, density, and function of GABAA receptors in the postsynaptic membrane.

AB - Neural inhibition in the brain is mainly mediated by ionotropic γ-aminobutyric acid type A (GABAA) receptors. Different subtypes of these receptors, distinguished by their subunit composition, are either concentrated at postsynaptic sites where they mediate phasic inhibition or found at perisynaptic and extrasynaptic locations where they prolong phasic inhibition and mediate tonic inhibition, respectively. Of special interest are mechanisms that modulate the stability and function of postsynaptic GABA A receptor subtypes and that are implicated in functional plasticity of inhibitory transmission in the brain. We will summarize recent progress on the classification of synaptic versus extrasynaptic receptors, the molecular composition of the postsynaptic cytoskeleton, the function of receptor-associated proteins in trafficking of GABAA receptors to and from synapses, and their role in post-translational signaling mechanisms that modulate the stability, density, and function of GABAA receptors in the postsynaptic membrane.

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