Glycine as a Neurotransmitter


Glycine serves as a major inhibitory neurotransmitter in the adult vertebrate central nervous system and is implicated in the control of many motor and sensory pathways. In addition, this amino acid functions as an excitatory transmitter during embryonic development and is an essential coagonist at glutamatergic synapses containing the N‐methyl‐d‐aspartate (NMDA) subtype of glutamate receptors.

Keywords: amino acid transmitter; glycine transport; glycine receptor; strychnine antagonism; inherited motor disorder

Figure 1.

Inhibitory and excitatory actions of glycine depend on the direction of glycine receptor (GlyR)‐mediated Cl flux. (a) In adult neurons, opening of GlyR channels causes Cl influx into the cytoplasm of the depolarized cell, due to a low concentration of intracellular Cl. This results in charge neutralization of intracellular Na+ ions, and thus inhibition of neuronal firing. (b) Owing to the high activity of a specific chloride exchange system, embryonic neurons contain a high concentration of intracellular Cl. Opening of the GlyR channel therefore leads to Cl efflux, and thereby an increase of intracellular positive charge, i.e. neuronal excitation.

Figure 2.

Chemical structures of natural inhibitory amino acids and strychnine. Left, the glycine receptor agonists glycine, ã‐alanine and taurine as well as γ‐aminobutyric acid (GABA) are shown. Note different distances between positively and negatively charged head groups. Right, structure of strychnine. The aromatic ring positions indicated by arrows can be substituted without losing toxicity; this has been exploited for affinity purification and the synthesis of fluorescent derivatives.


Further Reading

Aprison MH (1990) The discovery of the neurotransmitter role of glycine. In: Ottersen OP and Storm‐Mathiesen J (eds) Glycine Neurotransmission, pp. 1–23. New York: Wiley.

Becker CM (1992) Convulsant acting at the inhibitory glycine receptor. In: Herken H and Hucho F (eds) Handbook of Experimental Pharmacology, vol. 102, pp. 539–575. Berlin: Springer.

Boehm S, Harvey RJ, v. Holst A, Rohrer H and Betz H (1997) Glycine receptors in cultured chick sympathetic neurons are excitatory and trigger neurotransmitter release. Journal of Physiology 504: 683–694.

Bormann J, Hamill OP and Sakmann B (1987) Mechanism of anion permeation through channels gated by glycine and γ‐aminobutyric acid in mouse cultured spinal neurones. Journal of Physiology 385: 243–286.

Harvey RJ and Betz H (2000) Structure, diversity, pharmacology and pathology of glycine receptor chloride channels. In: Endo M, Kurachi Y and Mishina M (eds) Handbook of Experimental Pharmacology, vol. 47, pp. 479–498. Berlin: Springer.

Maycox PR, Hell JW and Jahn R (1990) Amino acid neurotransmission: spotlight on synaptic vesicles. Trends in Neurosciences 13: 83–87.

Rajendra S and Schofield PR (1995) Molecular mechanisms of inherited startle syndromes. Trends in Neurosciences 18: 80–82.

Schloss P, Püschel AW and Betz H (1994) Neurotransmitter transporters: new members of known families. Current Opinion in Cell Biology 6: 595–599.

Shiang R, Ryan SG, Zhu YZ et al. (1993) Mutations in the α1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nature Genetics 5: 351–360.

Wang J, Reichling D, Kyrozis A and MacDermott AB (1994) Developmental loss of GABA‐ and glycine‐induced depolarization and Ca2+ transients in embryonic rat dorsal horn neurons in culture. European Journal of Neuroscience 6: 1275–1280.

Young AB and Snyder SH (1973) Strychnine binding associated with glycine receptors of the central nervous system. Proceedings of the National Academy of Sciences of the USA 70: 2832–2836.

Zarbin MA, Wamsley JK and Kuhar MJ (1981) Glycine receptor: light microscopic autoradiographic localization with [3H]strychnine. Journal of Neuroscience 1: 532–547.

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Betz, Heinrich, and Harvey, Robert J(Apr 2001) Glycine as a Neurotransmitter. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000140]