Glycine receptor

The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brain stem.

The receptor can be activated by a range of simple amino acids including glycine, β-alanine and taurine, and can be selectively blocked by the high-affinity competitive antagonist strychnine. Caffeine has recently been found to also be a competitive antagonist.

Arrangement of subunits
Strychnine-sensitive glycine receptors are members of a family of Ligand-gated ion channels. Receptors of this family are arranged as five subunits surrounding a central pore, with each subunit composed of four α helical transmembrane segments.

There are presently four known isoforms of the α-subunit (α1-4) of GlyR that are essential to bind ligands and a single β-subunit.

The adult form of the GlyR is the heteromeric α1β receptor, which is believed to have a stoichiometry (proportion) of three α1 subunits and two β subunits or four α1 subunits and one β subunit. The α-subunits are also able to form functional homo-pentameric receptors in heterologous expression systems in African clawed frog's oocytes or mammalian cell lines, and the α1 homomeric receptor is essential for studies of channel pharmacokinetics and pharmacodynamics.

Glycine receptors in diseases
Disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions results in the rare neurological disorder, hyperekplexia. The disorder is characterized by an exaggerated response to unexpected stimuli which is followed by a temporary but complete muscular rigidity often resulting in an unprotected fall. Chronic injuries as a result of the falls are symptomatic of the disorder. A mutation in GLRA1 is responsible for some cases of stiff person syndrome.

Research
Quantum dots have been used to track the diffusion of glycine receptors into the synapse of neurons.

Formation of the mature GlyR complex at the post-synaptic membrane was found to be reliant on presence of a protein called gephyrin, via knockout studies in mice.

Agonists

 * Alanine
 * Cycloserine
 * Dimethylglycine
 * Glycine
 * Hypotaurine
 * Methylglycine (Sarcosine)
 * Milacemide
 * Serine
 * Taurine
 * Trimethylglycine (Betaine)

Antagonists

 * Bicuculline
 * Brucine
 * Caffeine
 * Picrotoxin
 * Strychnine
 * Tutin