Journal
NEUROPHARMACOLOGY
Volume 56, Issue 1, Pages 303-309Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2008.07.034
Keywords
Chloride channel; Inhibitory synaptic transmission; Ligand-gated ion channel; Cys-loop receptor
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Funding
- National Health and Medical Research Council of Australia
- Australian Research Council
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The glycine receptor chloride channel (GlyR), a member of the pentameric Cys-loop ion channel receptor family, mediates inhibitory neurotransmission in the spinal cord, brainstem and retina. They are also found presynaptically, where they modulate neurotransmitter release. Functional GlyRs are formed from a total of five subunits (alpha 1 -alpha 4, beta). Although alpha subunits efficiently form homomeric GlyRs in recombinant expression systems, homomeric alpha 1, alpha 3 and alpha 4 GlyRs are weakly expressed in adult neurons. in contrast, alpha 2 homomeric GlyRs are abundantly expressed in embryonic neurons, although their numbers decline sharply by adulthood. Numerous lines of biochemical, biophysical, pharmacological and genetic evidence suggest the majority of glycinergic neurotransmission in adults is mediated by heteromeric alpha 1 beta GlyRs. Immunocytochemical co-localisation experiments suggest the presence of alpha 2 beta, alpha 3 beta and alpha 4 beta GlyRs at synapses in the adult mouse retina. Immunocytochemical and electrophysiological evidence also implicates alpha 3 beta GlyRs as important mediators of glycinergic inhibitory neurotransmission in nociceptive sensory neuronal circuits in peripheral laminae of the spinal cord dorsal horn. It is yet to be determined why multiple Glyl? synaptic subtypes are differentially distributed in these and possibly other locations. The development of pharmacological agents that can discriminate strongly between different beta subunit-containing GlyR isoforms will help to address this issue, and thereby provide important insights into a variety of central nervous system functions including retinal signal processing and spinal pain mechanisms. Finally, agents that selectively potentiate different GlyR isoforms may be useful as therapeutic lead compounds for peripheral inflammatory pain and movement disorders such as spasticity. (C) 2008 Elsevier Ltd. All rights reserved.
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