Lynch JW. Native glycine receptor subtypes and their physiological roles. Neuropharmacology 56: 303-309

Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia.
Neuropharmacology (Impact Factor: 5.11). 09/2008; 56(1):303-9. DOI: 10.1016/j.neuropharm.2008.07.034
Source: PubMed


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 (alpha1-alpha4, beta). Although alpha subunits efficiently form homomeric GlyRs in recombinant expression systems, homomeric alpha1, alpha3 and alpha4 GlyRs are weakly expressed in adult neurons. In contrast, alpha2 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 alpha1beta GlyRs. Immunocytochemical co-localisation experiments suggest the presence of alpha2beta, alpha3beta and alpha4beta GlyRs at synapses in the adult mouse retina. Immunocytochemical and electrophysiological evidence also implicates alpha3beta 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 GlyR 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.

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    • "Glycine receptors are heteropentameric ligand-gated chloride ion channels that facilitate fast inhibitory neurotransmission in the human central nervous system (Lynch, 2009). Glycinergic synapses have a well-established role in the regulation of locomotor behavior. "
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    ABSTRACT: The Spontaneously Hypertensive Rat (SHR) strain is a classical animal model for the study of essential hypertension. Recently, our group suggested that this strain could be a useful animal model for schizophrenia, which is a severe mental illness with involvement of glutamatergic system. The aim of this study is to investigate glutamatergic receptors (Gria1 and Grin1) and glycine transporter (Glyt1) gene expression in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of SHR animals. The effects in gene expression of a chronic treatment with antipsychotic drugs (risperidone, haloperidol and clozapine) were also analyzed. Animals were treated daily for 30 days, and euthanized for brain tissue collection. The expression pattern was evaluated by Real Time Reverse-Transcriptase (RT) PCR technique. In comparison to control rats, SHR animals present a lower expression of both NMDA (Grin1) and AMPA (Gria1) gene receptors in the NAcc. Antipsychotic treatments were not able to change gene expressions in any of the regions evaluated. These findings provide evidence for the role of glutamatergic changes in schizophrenia-like phenotype of the SHR strain. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    08/2015; 229(3):PSYD1500347. DOI:10.1016/j.psychres.2015.08.021
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    • "id we have focused on possible interaction sites for this compound inside different GlyR domains . In previous studies it has been shown that most of the residues that are responsible for GlyR modulation by ions , cannabinoids , alcohols , and anesthetics are located in the extracellular domain , in the TM2 and TM3 domains ( Mihic et al . , 1997 ; Lynch et al . , 1998 ; Maksay et al . , 2009 ; Yevenes and Zeilhofer , 2011b ) ."

    SpringerPlus 06/2015; 4(Suppl 1):L31. DOI:10.1186/2193-1801-4-S1-L31
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    • "It should be noted however , that these electrophysiological recordings were performed in paralyzed animals, therefore we cannot exclude the possibility that the activity of spinal sensory neurons (such as RBs) and interneurons could be different when the muscles are physically contracting. The embryonic mammalian α2 glycine receptor subunit imparts slow decay time constants on homomeric α2 and heteromeric α2β glycine receptors (for reviews see Legendre, 2001; Lynch, 2004, 2009). We observed that the glycinergic mPSCs of CoPAs exhibit similarly slow kinetics, suggesting that glycine receptors contain α2 or similar (α4a) subunits. "
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    ABSTRACT: In all but the simplest monosynaptic reflex arcs, sensory stimuli are encoded by sensory neurons that transmit a signal via sensory interneurons to downstream partners in order to elicit a response. In the embryonic zebrafish (Danio rerio), cutaneous Rohon-Beard (RB) sensory neurons fire in response to mechanical stimuli and excite downstream glutamatergic commissural primary ascending (CoPA) interneurons to produce a flexion response contralateral to the site of stimulus. In the absence of sensory stimuli, zebrafish spinal locomotor circuits are spontaneously active during development due to pacemaker activity resulting in repetitive coiling of the trunk. Self-generated movement must therefore be distinguishable from external stimuli in order to ensure the appropriate activation of touch reflexes. Here, we recorded from CoPAs during spontaneous and evoked fictive motor behaviors in order to examine how responses to self-movement are gated in sensory interneurons. During spontaneous coiling, CoPAs received glycinergic inputs coincident with contralateral flexions that shunted firing for the duration of the coiling event. Shunting inactivation of CoPAs was caused by a slowly deactivating chloride conductance that resulted in lowered membrane resistance and increased action potential threshold. During spontaneous burst swimming, which develops later, CoPAs received glycinergic inputs that arrived in phase with excitation to ipsilateral motoneurons and provided persistent shunting. During a touch stimulus, short latency glutamatergic inputs produced cationic currents through AMPA receptors that drove a single, large amplitude action potential in the CoPA before shunting inhibition began, providing a brief window for the activation of downstream neurons. We compared the properties of CoPAs to those of other spinal neurons and propose that glycinergic signaling onto CoPAs acts as a corollary discharge signal for reflex inhibition during movement.
    Frontiers in Neural Circuits 09/2014; 8:121. DOI:10.3389/fncir.2014.00121 · 3.60 Impact Factor
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