The Inhibitory Glycine Receptor

The physiological function of the central nervous system (CNS) depends on a balance of excitatory and inhibitory neuronal impulses. Although GABA serves as a major inhibitory neurotransmitter in cortex and cerebellum, glycine is the principal inhibitory transmitter in the lower parts of the CNS, where it is involved in the segmental regulation of spinal motoneurons by small inter-neurons, including the Renshaw cells.' Thus, glycine is present at high levels in the anterior horn of the grey matter,* and immunodetection has permitted a detailed analysis of its cellular and subcellular distribution. These studies show that glycine is enriched in terminals of spinal cord interneurons, whereas cholinergic motoneurons are immunonegative. In addition, the presence of glycine has been demonstrated in brain stem nuclei, including auditory and vestibular center^.^.^ Upon its release by the presynaptic terminal, glycine binds to postsynaptic receptors located on the neuronal surface. Binding of glycine to its receptor induces the opening of an intrinsic anion channel, resulting in chloride currents and a postsynaptic hyperp~larization.~ Receptor binding of glycine is competitively antagonized by the plant alkaloid strychnine. Consistent with the physiology of glycinergic synapses, sublethal strychnine poisoning causes motor disturbances, for example, hyperreflexia and increases in muscle tonus. Further symptoms of strychnine intoxication include impairment of sensory, visual, and acoustic perception. Higher doses of strychnine lead to convulsions and death.6