Glycine receptors (GlyRs) mediate ionotropic inhibitory neurotransmission in the CNS where they play an essential role in inhibition of motor neurons in the spinal cord and brainstem1. The glycine receptor is composed of three ligand-binding subunits of 48 kDa (α) and two homologous polypeptides of 58 kDa (β) that span the postsynaptic membrane in a pentameric arrangement to form a Cl--selective channel2. So far, at least three different α-subunit variants of the GlyR have been identified: α1, α2 and α33. Homo-oligomeric α2 receptors have a low strychnine-binding affinity and are considered to represent a neonatal form of GlyR, which is replaced during development by receptors containing the α1 subunit. Adult GlyRs are predominantly composed of α1 and β subunits, the α3 subunit being expressed at low levels in only a few brain regions4.
GlyRα1 subunits are widely expressed and contribute to many processes in the CNS, including inflammatory pain perception, modulation of auditory and visual pathways, and neurotransmission in the cerebellar cortex5.
Mutations in glycine receptor α1 subunits cause human hereditary hyperekplexia, a disorder characterized by an exaggerated startle response, which is a consequence of the role of GlyRs in motor reflex circuits of the spinal cord6.
