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Handbook of Neurochemistry and Molecular Neurobiology pp 375–390Cite as

Inhibitory Glycine Receptors

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Abstract

The glycine receptor (GlyR) is a major inhibitory ligand-gated ion channel in the vertebrate central nervous system (CNS) that controls both motor and sensory pathways. This pentameric membrane protein is composed of α and β subunits that span the postsynaptic membrane and form a central anion-selective channel. Molecular cloning has identified four genes coding for α subunits and one gene coding for the β subunit whose differential expression generates distinct GlyR subtypes in the mammalian CNS. Alternative splicing and RNA editing extend the heterogeneity of GlyR subunits and significantly complicate GlyR pharmacology. Recent structural insights from the X-ray structures of homologous receptor proteins complemented by modeling studies have allowed to interprete available mutational and pharmacological data and provided important clues to ligand binding and ion permeation mechanisms. GlyR mutations cause neuromotor diseases, and specific GlyR subtypes have been implicated in the regulation of pain perception. Hence, the rational design of GlyR active compounds might produce drugs with subtype-selective properties and therapeutic potential. This review summarizes recent data on the molecular organisation, ligand binding sites, ion channel region, expression and functions of GlyRs as well as on human disorders associated with defects in GlyR function and glycine neurotransmission.

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Abbreviations

GABA:

γ-aminobutyric acid

NMDA:

N-methyl-d-aspartate

GABAA :

gamma-aminobutyric acid type-A

nAChR:

nicotinic acetylcholine receptor

ECD:

extracellular domain

AChBP:

acetylcholine-binding protein

SCAM:

substituted cysteine accessibility method

sIPSCs:

spontaneous inhibitory postsynaptic currents

PGE2 :

prostaglandin E2; 5HT; receptor, serotonin type 3 receptor

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Authors
  1. S. Dutertre
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  2. D. Kuzmin
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  3. B. Laube
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  4. H. Betz
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Group Director of Neuro-Developmental Disorder Research Group, RIKEN Brain Science Institute, 351-0198, 2-1 Hirosawa Wako-shi, Saitama, Japan

    Katsuhiko Mikoshiba

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Dutertre, S., Kuzmin, D., Laube, B., Betz, H. (2009). Inhibitory Glycine Receptors. In: Lajtha, A., Mikoshiba, K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30370-3_20

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