Figure 1.

Glycine signalling in macroglial cells. In macroglial cells, NKCC activity leads to intracellular chloride accumulation. Upon ligand binding, GlyR activation causes chloride efflux leading to cellular depolarization (which is further enhanced by electrogenic GlyT activity). This depolarization then activates VGCC. The resulting calcium influx increases the intracellular calcium concentration inducing several downstream effects (e.g. cell proliferation, migration and differentiation). Endocytosis of GlyRs might inactivate these receptors, explaining discrepancies between molecular and functional findings. Although cell culture conditions appear to have an influence on GlyR functionality and possibly endocytosis, the molecular mechanisms regulating of GlyR endocytosis are unknown.