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Molecular Organization of the Postsynaptic Membrane at Inhibitory Synapses

  • I. Lorena Arancibia-Carcamo
  • Antoine Triller
  • Josef T. Kittler

Abstract

The majority of fast inhibitory neurotransmission in the mammalian central nervous system (CNS) is mediated by γ-aminobutyric acid type A receptors (GABAA receptors), whereas in the brain stem and spinal cord fast inhibition is primarily mediated by glycine receptors where they can be associated with GABAA receptors at mixed synapses. GABAA receptors and glycine receptors are pentameric hetero-oligomeric ligand gated ion channels, the activation of which leads to the opening of an integral chloride permeable channel (Fig. 1). When chloride is low intracellularly, as in most adult neurons, this results in a chloride influx into the cell, resulting in cell hyperpolarization, moving the membrane potential away from the spike threshold for action potential generation. GABAA receptors and glycine receptors play a key role in regulating neuronal excitability, therefore modulating their function has important implications for regulating cell and network activity in the nervous system. In addition GABAA receptors are drug targets for many clinically relevant compounds including benzodiazepines, barbiturates, ethanol, neurosteroids and some anesthetics. Alterations in GABAA receptor and glycine receptor function have been implicated in an increasing number of neurological and neuropsychiatric diseases including: anxiety, depression, schizophrenia, epilepsy, stroke, substance abuse, neuropathic pain and hyperekplexia/startle disease. Correct synaptic inhibition is dependent on the formation and maintenance of inhibitory postsynaptic domains where postsynaptic GABA and/or glycine receptors can be recruited and stabilized below release sites for their cognate neurotransmitter. The formation and maintenance of inhibitory synapses depends on the dynamic recruitment of cell adhesion molecules and scaffold proteins to sites opposing inhibitory presynaptic terminals. In addition, the correct function of inhibitory synapses is

Keywords

GABAA Receptor Receptor Subunit Postsynaptic Membrane Glycine Receptor Inhibitory Synapse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • I. Lorena Arancibia-Carcamo
    • 1
  • Antoine Triller
    • 2
  • Josef T. Kittler
    • 3
  1. 1.Department of PharmacologyUniversity College LondonLondonUK
  2. 2.Biologie Cellulaire de la Synapse N&PInserm UR497Paris
  3. 3.Department of PhysiologyUniversity College LondonLondonUK

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