Glycine and glycine receptor signalling in non-neuronal cells.

Jimmy Van Den Eynden,Jean-Michel Rigo,Sofie Carmans,Paul Steels,Bert Brône,Robert J Harvey,Nikki Horwood,Sheen Saheb Ali,Niels Hellings

doi:10.3389/neuro.02.009.2009

Jimmy Van Den Eynden, Jean-Michel Rigo + Show 7 more

Open Access

https://doi.org/10.3389/neuro.02.009.2009

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Abstract

Glycine is an inhibitory neurotransmitter acting mainly in the caudal part of the central nervous system. Besides this neurotransmitter function, glycine has cytoprotective and modulatory effects in different non-neuronal cell types. Modulatory effects were mainly described in immune cells, endothelial cells and macroglial cells, where glycine modulates proliferation, differentiation, migration and cytokine production. Activation of glycine receptors (GlyRs) causes membrane potential changes that in turn modulate calcium flux and downstream effects in these cells. Cytoprotective effects were mainly described in renal cells, hepatocytes and endothelial cells, where glycine protects cells from ischemic cell death. In these cell types, glycine has been suggested to stabilize porous defects that develop in the plasma membranes of ischemic cells, leading to leakage of macromolecules and subsequent cell death. Although there is some evidence linking these effects to the activation of GlyRs, they seem to operate in an entirely different mode from classical neuronal subtypes.

Highlights

Glycine is one of the main components that mediate fast inhibitory neurotransmission in the central nervous system (CNS)
Since fluorimetric measurements showed that LPS depolarized Kupffer cells while glycine hyperpolarized them, it was suggested that glycine receptors (GlyRs)-dependent hyperpolarization leads to an inhibition of functional voltage-gated calcium channels (VGCCs), which were found in Kupffer cells (Hijioka et al, 1992)
Numerous in vitro and in vivo studies provide evidence for a cytoprotective role of glycine against kidney ischemia. This effect seems to be mediated by GlyRs with unusual properties: (i) there is little evidence that GlyR α subunits are expressed in kidney cell types, (ii) glycine effects can be mimicked by both GlyR agonists and antagonists and (iii) these effects do not depend upon the chloride gradient

Summary

INTRODUCTION

Glycine is one of the main components that mediate fast inhibitory neurotransmission in the central nervous system (CNS). Our group found molecular evidence for GlyR expression in different oligodendroglial cell lines (MO3.13, OLN-93, HOG), the receptors appear to show a cytoplasmic location, which might explain why we could not detect any GlyR-mediated ionic currents (Sahebali et al, 2007). Glycine-induced depolarization was substantial (up to +30 mV) despite the low amplitude of the currents (around 10 pA), and could be explained by the high membrane resistance of microglial cells (Newell and Schlichter, 2005) These data suggest that functional GlyRs are not present on microglial cells, our group recently provided molecular evidence for α and β GlyR subunit and gephyrin expression in these cells Future research on brain or spinal cord slices and GlyR trafficking will be necessary to examine this hypothesis

CONCLUSION

Findings