Influence of NMDA Receptor Antagonists on Glycine Receptor Isoform Expression in Spinal Cord Cultures

  • C.-M. Becker
  • W. Hoch
  • M. Schramm
  • I. Wolters
  • H. Betz
Conference paper


The physiology of the amino acid transmitter glycine is well characterized in spinal cord, where it is involved in both mutual and feedback inhibition by recurrent axon collaterals of spinal motoneurons. Glycinergic inhibition is mediated by small interneurons within the spinal gray matter, including the Renshaw cells (Aprison and Daly 1978). Upon its release by the inhibitory neuron, glycine binds to postsynaptic receptors where it causes an intrinsic chloride channel to open. The resulting chloride influx produces a postsynaptic hyperpolarization and drastically decreases neuronal firing (Bormann et al. 1987). Glycinergic inhibition is also found in spinal nociceptive, brain stem auditory, and other CNS systems as well as in the retina (reviewed by Becker 1992). The convulsant alkaloid strychnine competitively antagonizes receptor binding of glycine, and, conversely, glycinedisplaceable [3H]strychnine binding has been established as a pharmacological probe of inhibitory glycine receptors. Heterogeneity is a widespread phenomenon of neurotransmitter receptors in the mammalian CNS (Betz 1990). Different isoforms have also been identified of the inhibitory glycine receptor (reviewed by Betz and Becker 1988; Langosch et al. 1990; Becker 1992). In contrast, high-affinity binding sites for [3H]glycine are distinct from inhibitory glycine receptors and are thought to reflect a regulatory domain of the N-methyl-D-aspartate (NMDA) receptor (Betz and Becker 1988; Monaghan et al. 1989; Moriyoshi et al. 1991).


NMDA Receptor NMDA Receptor Antagonist Glycine Receptor Spinal Cord Neuron Mouse Spinal Cord 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aprison MH, Daly EC (1978) Biochemical aspects of transmission at inhibitory synapses: the role of glycine. Adv Neurochem 3: 203–294Google Scholar
  2. Becker C-M (1992) Selective neurotoxicity: convulsants acting at the inhibitory glycine receptor. In: Herken H, Hucho F (eds), Handbook of experimental pharmacology, vol 102. Springer, Berlin Heidelberg New York pp 539–575Google Scholar
  3. Becker C-M, Hermans-Borgmeyer I, Schmitt B, Betz H (1986) The glycine receptor deficiency of the mutant mouse spastic: evidence for normal glycine receptor structure and localization. J Neurosci 6: 1358–1364PubMedGoogle Scholar
  4. Becker C-M, Hoch W, Beta H (1988) Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J 7: 3717–3726PubMedGoogle Scholar
  5. Becker C-M, Schmieden V, Tarroni P, Strasser U, Betz H (1992) Isoform–selective deficit of glycine receptors in the mouse mutant spastic. Neuron 8: 283–289PubMedCrossRefGoogle Scholar
  6. Betz H (1990) Ligand–gated ion channels in the brain: the amino acid receptor family. Neuron 5: 383–392PubMedCrossRefGoogle Scholar
  7. Betz H, Becker C-M (1988) The mammalian glycine receptor: biology and structure of a neuronal chloride channel protein. Neurochem Int 13: 137–146PubMedCrossRefGoogle Scholar
  8. Bormann J, Hamill OP, Sakmann B (1987) Mechanism of anion permeation through channels gated by glycine and y-–aminobutyric acid in mouse cultured spinal cord neurons. J Physiol (Lond) 385: 243–286Google Scholar
  9. Choi D (1990) The role of glutamate in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13: 171–182PubMedCrossRefGoogle Scholar
  10. Fonnum F (1975) A rapid radiochemical method for the determination of choline acetyl transferase. J Neurochem 24: 407–409PubMedCrossRefGoogle Scholar
  11. Geyer SW, Gudden W, Betz H, Gnahn H, Weindl A (1987) Colocalization of choline acetyltransferase and postsynaptic glycine receptors in motoneurons of rat spinal cord demonstrated by immunocytochemistry. Neurosci Lett 82: 11–15PubMedCrossRefGoogle Scholar
  12. Grenningloh G, Rienitz A, Schmitt B, Methfessel C, Zensen M, Beyreuther K, Gundelfinger ED, Betz H (1987) The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature 328: 215–220PubMedCrossRefGoogle Scholar
  13. Grenningloh G, Pribilla I, Prior P, Multhaup G, Beyreuther K, Taleb O, Betz H (1990) Cloning and expression of the 58 kd beta subunit of the inhibitory glycine receptor. Neuron 4: 963–970PubMedCrossRefGoogle Scholar
  14. Hamill OP, Bormann J, Sakmann B (1983) Activation of multiple-conductance state chloride channels in spinal neurones by glycine and GAB A. Nature 305: 805–808PubMedCrossRefGoogle Scholar
  15. Hoch H, Betz H, Becker C-M (1989) Primary cultures of mouse spinal cord express the neonatal isoform of the inhibitory glycine receptor. Neuron 3: 339–348PubMedCrossRefGoogle Scholar
  16. Hoch W, Betz H, Schramm M, Wolters I, Becker C-M (1992) Modulation by NMDA-receptor antagonists of glycine receptor isoform expression in cultured spinal cord neurons. Eur J Neurosci 4: 389–395PubMedCrossRefGoogle Scholar
  17. Kuhse J, Schmieden V, Betz H (1990a) A single amino acid exchange alters the pharmacology of neonatal rat glycine receptor subunit. Neuron 5: 867–873PubMedCrossRefGoogle Scholar
  18. Kuhse J, Schmieden V, Betz H (1990b) Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor. J Biol Chem 265: 22317 - 22320PubMedGoogle Scholar
  19. Kuhse J, Kuryatov A, Maulet Y, Malosio M-L, Schmieden V, Betz H (1991) Alternative splicing generates two isoforms of the al subunit of the inhibitory glycine receptor. FEBS Lett 283: 73–77PubMedCrossRefGoogle Scholar
  20. Langosch D, Becker C-M, Betz H (1990) The inhibitory glycine receptor: a ligand–gated chloride channel of the central nervous system. Eur J Biochem 194: 1–8PubMedCrossRefGoogle Scholar
  21. Malosio M–L, Marqueze–Pouey B, Kuhse J, Betz H (1991) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J 10: 2401–2409Google Scholar
  22. Monaghan DT, Bridges RJ, Cotman CW (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol 29: 365–402PubMedCrossRefGoogle Scholar
  23. Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354: 31–37PubMedCrossRefGoogle Scholar
  24. Naas E, Zilles K, Gnahn H, Betz H, Becker C-M, Schroder H (1991) Glycine receptor immunoreactivity in cerebral cortex of man and rat. Brain Res 561: 139–146PubMedCrossRefGoogle Scholar
  25. Pfeiffer F, Graham D, Betz H (1982) Purification by affinity chromatography of the glycine receptor of rat spinal cord. J Biol Chem 257: 9389–9393PubMedGoogle Scholar
  26. Pfeiffer F, Simler R, Grenningloh G, Betz H (1984) Monoclonal antibodies and peptide mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord. Proc Natl Acad Sci USA 81: 7224–7227PubMedCrossRefGoogle Scholar
  27. Prior P, Schmitt B, Grenningloh G, Pribilla I, Multhaup G, Beyreuther K, Maulet Y, Werner P, Langosch D, Kirsch J, Betz H (1992) Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein. Neuron 8: 1161–1170PubMedCrossRefGoogle Scholar
  28. Ransom B, Bullock PN, Nelson PG (1977) Mouse spinal cord in cell culture. III. Neuronal chemosensitivity and its relationship to synaptic activity. J Neurophysiol 40: 1163–1177Google Scholar
  29. Schmieden V, Grenningloh G, Schofield PR, Betz H (1989) Functional expression in Xenopus oocytes of the strychnine binding 48 kd subunit of the glycine receptor. EMBO J 8: 695–700PubMedGoogle Scholar
  30. Schramm M, Eimerl S, Costa E (1990) Serum and depolarizing agents cause acute neurotoxicity in cultured cerebellar granule cells: role of glutamate receptor responsive to N-methyl-Daspartate. Proc Natl Acad Sci USA 87: 1193–1197PubMedCrossRefGoogle Scholar
  31. Schroder S, Hoch W, Becker C-M, Grenningloh G, Betz H (1991) Mapping of antigenic epitopes on the al subunit of the inhibitory glycine receptor. Biochemistry 30: 42–47PubMedCrossRefGoogle Scholar
  32. Sontheimer H, Becker C-M, Pritchett DP, Schofield PR, Grenningloh G, Kettenmann H, Betz H, Seeburg PH (1989) Functional chloride channels by mammalian cell expression of rat glycine receptor subunit. Neuron 2: 1491–1497PubMedCrossRefGoogle Scholar
  33. Telcoma ES, Monyer H, Goldberg MP, Choi DW (1989) Traumatic neuronal injury is attenuated by NMDA antagonists in vivo. Neuron 2: 1541–1545CrossRefGoogle Scholar
  34. Triller A, Cluzeaud F, Pfeiffer F, Betz H, Korn H (1985) Distribution of glycine receptors at central synapses: an immunoelectron microscopy study. J Cell Biol 101: 683–688PubMedCrossRefGoogle Scholar
  35. Wiedenmann B, Franke WW (1985) Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell 41: 1017–1028PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • C.-M. Becker
    • 1
    • 2
  • W. Hoch
    • 1
    • 5
  • M. Schramm
    • 3
  • I. Wolters
    • 2
    • 4
  • H. Betz
    • 4
  1. 1.Neurologische UniversitätsklinikUniversität HeidelbergHeidelbergGermany
  2. 2.Zentrum für Molekulare BiologieUniversität HeidelbergHeidelbergGermany
  3. 3.Department of Biological ChemistryHebrew University of JerusalemJerusalemIsrael
  4. 4.Max-Planck-Institut für HirnforschungFrankfurtGermany
  5. 5.Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Beckman CenterStanford UniversityStanfordUSA

Personalised recommendations