Excitatory Amino Acids: Membrane Physiology

  • Mark L. Mayer
  • Gary L. Westbrook


The excitatory action of acidic amino acids on neuronal membranes was first revealed in electrophysiological studies on cortical neurons (Hayashi, 1954) and, subsequently, on spinal neurons (Curtis et al., 1960). Amino acids such as l-glutamate and l-aspartate excite neurons in virtually every area of the vertebrate nervous system with the exception of those in sensory and autonomic ganglia. A large number of other acidic amino acids, including the sulphur-containing analogs cysteic and homocysteic acids, are also potent excitatory substances, and since the optical isomers of aspartate, glutamate and homocysteate show relatively little difference in potency it is easy, in retrospect, to appreciate the disappointment this lack of specificity must have generated. This ubiquitous excitatory action of acidic amino acids initially led Curtis and Watkins (1960) to suggest that these substances were unlikely to act as synaptic transmitters.


NMDA Receptor Excitatory Amino Acid Acidic Amino Acid Voltage Sensitivity Excitatory Amino Acid Receptor 
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  1. Ault, B., Evans, R. H., Francis, A. S., Oakes, D. J., and Watkins, J. C., 1980, Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations, J. Physiol. (Lond.) 307: 413–428.Google Scholar
  2. Brown, T. H., and Johnston, D., 1983, Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurones, J. Neurophysiol. 50: 487–507.PubMedGoogle Scholar
  3. Buhrle, Ch. Ph., and Sonnhof, U., 1983, The ionic mechanism of the excitatory action of glu- tamate upon the membrane of motoneurones of the frog, Pflügers Arch. 396: 154–162.PubMedCrossRefGoogle Scholar
  4. Collingridge, G. L., Kehl, S. J., and McLennan, H., 1983, Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus, J. Physiol. (Lond.). 334: 33–46.Google Scholar
  5. Coombs, J. S., Eccles, J. C., and Fatt, P., 1955, Excitatory synaptic action on motoneurones, J. Physiol. (Lond.) 130: 374–395.Google Scholar
  6. Crunelli, V., Forda, S., and Kelly, J. S., 1983, Blockade of amino acid-induced depolarizations and inhibition of excitatory post-synaptic potentials in rat dentate gyrus, J. Physiol. (Lond.) 341: 627–640.Google Scholar
  7. Crunelli, V., and Mayer, M. L., 1984, Mgt dependence of membrane resistance increases evoked by NMDA in hippocampal neurones, Brain Res. 311: 392–396.PubMedCrossRefGoogle Scholar
  8. Curtis, D. R., Phillis, J. W., and Watkins, J. C., 1960, The chemical excitation of spinal neurones by certain acidic amino acids, J. Physiol. (Lond.) 150: 656–682.Google Scholar
  9. Curtis, D. R., and Watkins, J. C.. 1960, The excitation and depression of spinal neurones by structurally related amino acids, J. Neurochem. 6: 117–141.PubMedCrossRefGoogle Scholar
  10. Dingledine, R., 1983, N-Methyl aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells, J. Physiol. (Lond.) 343: 385–405.Google Scholar
  11. Engberg, I., Flatman, J. A., and Lambert, J. D. C., 1978, The action of N-methyl-n-aspartic and kainic acids on motoneurones with emphasis on conductance changes, Br. J. Pharmacol. 64: 384–385 P.Google Scholar
  12. Enberg, I., Flatman, J. A., and Lambert, J. D. C., 1979, The actions of excitatory amino acids on motoneurons in the feline spinal cord, J. Physiol (Lond.) 288: 227–261.Google Scholar
  13. Engberg, I., and Marshall, K. C., 1979, Reversal potential for la excitatory post-synaptic potentials in spinal motoneurones of cats, Neuroscience 4: 1383–1591.CrossRefGoogle Scholar
  14. Finkel, A. S., and Redman, S. J., 1983, The synaptic current evoked in cat spinal motoneurones by impulses in single group la axons, J. Physiol. (Lond.) 342: 615–632.Google Scholar
  15. Flatman, J. A., Schwindt, P. C., Crill, W. E., and Stafstrom, C. E., 1983, Multiple actions of N-methyl-n-aspartate on cat neocortical neurones in vitro, Brain Res. 266: 166–173.CrossRefGoogle Scholar
  16. Gorman, A. L. F., Hermann, A., and Thomas, M. V., 1981, Intracellular calcium and the control of neuronal pacemaker activity, Fed. Proc. 40: 2233–2239.PubMedGoogle Scholar
  17. Hablitz, J. J., and Langmoen, I. A., 1982, Excitation of hippocampal pyramidal cells by glutamate in the guinea pig and rat, J. Physiol. (Lond.) 325: 317–331.Google Scholar
  18. Hayashi T., 1954, Effects of sodium glutamate on the nervous system, Keio J. Med. 3: 183–192.CrossRefGoogle Scholar
  19. Hodgkin, A. L. and Huxley, A. F., 1952, A quantitative description of membrane current and its application to conduction and excitation in nerve, J. Physiol. (Loud.) 117: 500–544.Google Scholar
  20. MacDonald, J. F., 1984, Substitution of extracellular sodium ions blocks the voltage-dependent decrease of input conductance evoked by L-aspartate, Can. J. Physiol. Pharmacol. 62: 109–115.CrossRefGoogle Scholar
  21. MacDonald, J. F., and Wojtowicz, J. M., 1982, The effects of glutamate and its analogues upon the membrane conductance of central murine neruones in culture, Can. J. Physiol. Pharmacol. 60: 282–296.CrossRefGoogle Scholar
  22. MacDonald, J. F., Porietis, A. V., and Wojtowicz, J. M., 1982, L-Aspartic acid induces a region of negative slope conductance in the current voltage relationship of cultured spinal cord neurones, Brain Res. 237: 248–253.PubMedCrossRefGoogle Scholar
  23. Macdonald, R. L., Pun, R. Y. K., Neale, E. A., and Nelson, P. G., 1983, Synaptic interactions between mammalian central neurons in cell culture. I. Reversal potentials for excitatory postsynaptic potentials, J. Neurophysiol. 49: 1428–1441.PubMedGoogle Scholar
  24. Magleby, K. L., and Stevens C. F., 1972, The effect of voltage on the time course of end-plate currents, J. Physiol. (Loud.) 223: 151–171.Google Scholar
  25. Mayer, M. L., and Westbrook, G. L., 1984, Mixed-agonist action of excitatory amino acids on mouse spinal cord neurones under voltage clamp, J. Physiol. (Lond.), 354: 29–53.Google Scholar
  26. Mayer, M. L, and Westbrook, G. L., 1985, The action of N-methyl-o-aspartic acid on mouse spinal neurones in culture, J. Physiol. (Loud.) 361: 65–90.Google Scholar
  27. Mayer, M. L., Westbrook, G. L., and Guthrie, P. B., 1984, Voltage-dependent block by Mg l’ of NMDA responses in spinal cord neurones, Nature, 309: 261–263.PubMedCrossRefGoogle Scholar
  28. Neale, E. A., Nelson, P. G., Macdonald, R. L., Christian, C. N., and Bowers, L. M., 1983, Synaptic interactions between mammalian central neurons in cell culture. III. Morphophysiological correlates of quantal synaptic transmission, J. Neurophysiol. 49: 1459–1468.PubMedGoogle Scholar
  29. Nelson, P. G., Marshall, K. C., Pun, R. Y. K., Christian, C. N., Sheriff, W. H., Jr., Macdonald, R. L., and Neale, E. A., 1983a, Synaptic interactions between mammalian central neurons in cell culture. II. Quantal analysis of Epsps, J. Neurophysiol. 49: 1442–1458.PubMedGoogle Scholar
  30. Nelson, P. G., Pun, R. Y. K., and Westbrook, G. L., 1983b, Monosynaptic excitatory postsynaptic potentials and responses to putative amino acid neurotransmitters in spinal cord cultures: A voltage clamp study, Soc. Neurosci. Abst. 9: 1144.Google Scholar
  31. Nowak, L. M. and Ascher, P., 1984, N-methyl-o-aspartic, kainic and quisqualic acids evoked currents in mammalian central neurones, Soc. Neurosci. Abst. 10: 23.Google Scholar
  32. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A., and Prochiantz, A. 1984, Magnesium gates glutamate-activated channels in mouse central neurones, Nature 307: 462–465.PubMedCrossRefGoogle Scholar
  33. Olverman, H. J., Jones, W. S., and Watkins, J. C., 1984, L-Glutamate has higher affinity than other amino acids for [3H]-D-AP5 binding sites in rat brain membranes, Nature 307: 460–462.PubMedCrossRefGoogle Scholar
  34. Redman, S. J., 1979, Junctional mechanisms at group la synapses, Prog. Neurobiol. 12: 33–83.Google Scholar
  35. Sawada, S., Takada, S., and Yamamoto, C., 1983. Selective activation of synapses near the tip of drug-ejecting microelectrode, and effects of antagonists of excitatory amino acids in the hippocampus, Brain Res. 267: 156–160.PubMedCrossRefGoogle Scholar
  36. Watkins, J. C., 1981, Pharmacology of excitatory amino acid receptors in: Glutamate: Transmitter in the Central Nervous System (P. J. Roberts, J. Storm-Mathisen, and G. A. R. Johnston, eds.) Wiley, New York, pp. 1–29.Google Scholar
  37. Westbrook, G. L., and Mayer, M. L., 1984, Glutamate currents in mammalian spinal neurones: Resolution of a paradox, Brain Res. 301: 375–379.PubMedCrossRefGoogle Scholar
  38. Woodhull, A. M., 1973, Ionic blockage of sodium channels in nerve, J. Gen. Physiol. 61:687–708.PubMedCrossRefGoogle Scholar
  39. Zieglgänsberger, W., and Puil, E. A., 1972, Tetrodotoxin interference of CNS excitation by glutamic acid, Nature New Biol. 234: 205–205.Google Scholar

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© Plenum Press, New York 1985

Authors and Affiliations

  • Mark L. Mayer
  • Gary L. Westbrook

There are no affiliations available

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