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Structure and Functions of Inhibitory and Excitatory Glycine Receptors
Author(s) -
BETZ HEINRICH,
KUHSE JOCHEN,
SCHMIEDEN VOLKER,
LAUBE BODO,
KIRSCH JOACHIM,
HARVEY ROBERT J.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb11343.x
Subject(s) - glycine receptor , strychnine , chloride channel , glycine , protein subunit , inhibitory postsynaptic potential , chemistry , cys loop receptors , gephyrin , microbiology and biotechnology , long term potentiation , receptor , ion channel , biophysics , biochemistry , neuroscience , biology , amino acid , gene , acetylcholine receptor , nicotinic acetylcholine receptor
The strychnine‐sensitive glycine receptor (GlyR) is a pentameric chloride channel protein that exists in several developmentally and regionally regulated isoforms in the CNS. These result from the differential expression of four genes encoding different variants (α1‐α4) of the ligand‐binding subunit of the GlyR. Their assembly with the structural b subunit is governed by “assembly cassettes” within the extracellular domains of these proteins and creates chloride channels of distinct conductance properties. GlyR gating is potentiated by Zn 2+ , a metal ion co‐released with different neurotransmitters. Site‐directed mutagenesis has unraveled major determinants of agonist binding and Zn 2+ potentiation. During development, glycine receptors mediate excitation that results in Ca 2+ influx and neurotransmitter release. Ca 2+ influx triggered by the activation of embryonic GlyRs is required for the synaptic localization of the GlyR and its anchoring protein gepyhrin. In the adult, mutations in GlyR subunit genes result in motor disorders. The spastic and spasmodic phenotypes in mouse as well as human hereditary startle disease will be discussed.