GlyRs

Glycine receptors (GlyRs) are pentameric ligand-gated chloride channels that mediate fast inhibitory neurotransmission in the central nervous system. They belong to the Cys-loop receptor superfamily, which also includes nicotinic acetylcholine receptors and GABA_A receptors. Activation occurs when glycine binds to high-affinity sites on the extracellular domain of α subunits, causing the channel to open and chloride ions to enter the neuron, leading to hyperpolarization and inhibition of action potential generation.

GlyRs are typically assembled as heteromeric pentamers composed of α and β subunits. In humans, the α subunits are encoded by GLRA1–GLRA4 genes, and the β subunit by GLRB. In the mature CNS, glycine receptors commonly contain α1 subunits with a β subunit, and the β subunit plays a key role in synaptic localization by binding to the scaffolding protein gephyrin at inhibitory postsynaptic densities.

Distribution and function extend across the spinal cord and brainstem, with expression in other regions and in certain retinal circuits. GlyRs contribute to the precise regulation of motor control, reflexes, and sensory processing by shaping inhibitory signaling in neural networks.

Pharmacology and clinical relevance include blockade by the plant alkaloid strychnine, which produces severe convulsions by removing inhibitory control of motor circuits. Receptor function can be modulated by zinc and other ions, and receptor kinetics vary with subunit composition.

Mutations in GLRA1 or GLRB can cause hyperekplexia (startle disease), a disorder characterized by exaggerated startle responses and stiffness in infancy. Treatments often aim to enhance inhibitory signaling, such as with benzodiazepines that augment GABAergic inhibition.