Advertisement

Blockade of Excitatory Amino Acid Transmitters and Epilepsy

  • J. F. MacDonald
  • Z. Miljkovic
  • J. H. Schneiderman

Abstract

The excitatory amino acids, and in particular L-glutamic acid (L-GlU), have long been considered possible transmitters in the mammalian CNS (Nistri and Constanti, 1979; Puil, 1981; Fagg and Foster, 1983). However, only recently have advances in the availability of the appropriate pharmacological tools, such as specific antagonists, stimulated a renewed interest in identification of these synapses (Jahr and Jessell, 1985; Jahr and Yoshioka, 1986; Nelson et al., 1986; Thomson, 1986). Initially, the remarkable ubiquity of neuronal responsiveness to L-G1U, together with its role in intermediate metabolism, brought into question a transmitter role for this substance (Curtis et al., 1960). In retrospect, it now seems that this characteristic may simply be a reflection of the ubiquity of excitatory amino acid transmission.

Keywords

NMDA Receptor Excitatory Amino Acid Spinal Cord Neurone NMDA Channel Anticonvulsant Property 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Albuquerque, E. X., Aguayo, L. G., Warnick, J. E., Ickowicz, R. K., and Blaustein, M. P., 1983, Interactions of phencyclidine with ion channels of nerve and muscle behavioural implications, Fed. Proc. 42:2584–2589.PubMedGoogle Scholar
  2. Alger, B. E., 1984, Hippocampus: Electrophysiological studies of epileptiform activity in vitro, in: Brain Slices (R.Dingledine, ed.), Plenum Press, New York, pp. 155–193.Google Scholar
  3. Anis, N. A., Berry, S. C., Burton, N. R., and Lodge, D., 1983, The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate, Br. J. Pharmacol. 79:565–575.PubMedGoogle Scholar
  4. Armstrong-James, M., Caan, A. W., and Fox, K., 1985, Threshold effects of N-methyl-D-aspartate (NMDA) and 2-amino-5-phosphonovaleric acid (2APV) on the spontaneous activity of neocortical single neurones in the urethane anaesthetised rat, Exp. Brain Res. 60:209–213.PubMedCrossRefGoogle Scholar
  5. Aronstam, R. S., Narayanan, L., and Wenger, D. A., 1982, Ketamine inhibition of ligand binding to cholinergic receptors and ion channels, Eur. J. Pharmacol. 78:367–370.PubMedCrossRefGoogle Scholar
  6. Bartschat, D. K., and Blaustein, M. P., 1986, Phencyclidine in low doses selectively blocks a presynaptic voltage-regulated potassium channel in rat brain, Proc. Natl. Acad. Sci. USA 83:189–192.PubMedCrossRefGoogle Scholar
  7. Callaghan, D. A., and Schwark, W. S., 1980, Pharmacological modifications of amygdaloid-kindled seizures, Neuropharmacology 19:1131–1136.PubMedCrossRefGoogle Scholar
  8. Celesia, G. G., and Chen, R. C., 1974, Effects of ketamine on EEG activity in cats and monkeys, Electroencephalogr. Clin. Neurophysiol. 37:345–353.CrossRefGoogle Scholar
  9. Chen, G., Ensor, C. R., and Bohner, B., 1966, The neuropharmacology of 2-(0-chlorophenyl)-2-methyl-amino-cyclohexanone hydrochloride, J. Pharmacol. Exp. Ther. 152:332–339.PubMedGoogle Scholar
  10. Colquhoun, D., and Hawkes, A. G., 1983, The principles of the stochastic interpretation of ion-channel mechanisms, in: Single Channel Recording (B. Sakmann and E. Neher, eds.), Plenum Press, New York, pp. 135–175.Google Scholar
  11. Connors, B. W., 1984, Initiation of synchronized neuronal bursting in neocortex, Nature 23:685–687.CrossRefGoogle Scholar
  12. Corssen, G., Little, S. C., and Tavakoli, M., 1974, Ketamine and epilepsy, Anesth. Analg. (Cleveland) 53:319–335.Google Scholar
  13. Courtney, K. R., 1975, Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA 968, J. Pharmacol. 195:225–236.Google Scholar
  14. Croucher, M. J., Collins, J. F., and Meldrum, B. S., 1982, Anticonvulsant action of excitatory amino acid antagonists, Science 216:889–901.CrossRefGoogle Scholar
  15. Curtis, D. R., Phillis, J. W., and Watkins, J. C., 1960, The chemical excitation of spinal neurones by certain acidic amino acids, J. Physiol. (London) 158:296–323.Google Scholar
  16. Davis, R. W., and Tolstoshev, G. C., 1976, Ketamine: Use in severe fibrile convulsions, Med. J. Aust. 63:465–466.Google Scholar
  17. Dingledine, R., 1983, N-Methyl aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells, J. Physiol. (London) 343:385–405.Google Scholar
  18. Duchen, M. R., Burton, N. R., and Biscoe, T. J., 1985, An intracellular study of the interactions of N-methyl-DL- aspartate with ketamine in the mouse hippocampal slice, Brain Res. 342:149–153.PubMedCrossRefGoogle Scholar
  19. Fagg, G. E., and Foster, A. C., 1983, Amino acid neurotransmitters and their pathways in the mammalian central nervous system, Neuroscience 9:701–719.PubMedCrossRefGoogle Scholar
  20. Flatman, J. A., Schwindt, P. C., Crill, W. E., and Stafstrom, C. E., 1983, Multiple actions of N-methyl-D- aspartate on cat neocortical neurons in vitro, Brain Res. 266:169–173.PubMedCrossRefGoogle Scholar
  21. Foster, A. C., and Fagg, G. E., 1984, Acidic amino acid binding sites in mammalian neuronal membranes: Their characteristics and relationship to synaptic receptors, Brain Res. 7:103–164.CrossRefGoogle Scholar
  22. Gage, P. W., and Robertson, B., 1985, Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus, Br. J. Pharmacol. 85:675–681.PubMedGoogle Scholar
  23. Gurney, A. M., and Rang, H. P., 1984, The channel-blocking action of methonium compounds on rat submandibular ganglion cells. Br. J. Pharmacol. 82:623–642.PubMedGoogle Scholar
  24. Hablitz, J. J., and Langmoen, I. A., 1986, N-methyl-D-aspartate receptor antagonists reduce synaptic excitation in the hippocampus, J. Neurosci. 6:102–106.PubMedGoogle Scholar
  25. Harrison, N. L., and Simmonds, M. A., 1985, Quantitative studies on some antagonists of N-methyl-D-aspartate in slices of rat cerebral cortex, Br. J. Pharmacol. 84:318–391.Google Scholar
  26. Hayashi, T., 1954, Effects of sodium glutamate on the nervous system, Keio J. Med. 3:183–192.Google Scholar
  27. Hayes, B. A., and Balster, R. L., 1985, Anticonvulsant properties of phencyclidine-like drugs in mice, Eur. J. Pharmacol. 117:121–125.PubMedCrossRefGoogle Scholar
  28. Herron, C. E., Lester, R. A. J., Coan, E. J., and Collingridge, G. L., 1985, Intracellular demonstration of an N- methyl-D-aspartate receptor mediated component of synaptic transmission in the rat hippocampus, Neurosci. Lett. 60:19–23.PubMedCrossRefGoogle Scholar
  29. Hille, B., 1984, Ionic Channels of Excitable Membranes, 1st ed., Sinauer Associates, Stanford.Google Scholar
  30. Honey, C. R., Miljkovic, Z., and MacDonald, J. F., 1985, Ketamine and phencyclidine cause a voltage-dependent block of responses to L-aspartic acid, Neurosci. Lett. 61:135–139.PubMedCrossRefGoogle Scholar
  31. Jahr, C. E., and Jessell, T. M., 1985, Synaptic transmission between dorsal root ganglion and dorsal horn neurons in culture: Antagonism of monosynaptic excitatory postsynaptic potentials and glutamate excitation by kynurenate, J. Neurosci. 5:2281–2289.PubMedGoogle Scholar
  32. Jahr, C. E., and Yoshioka, K., 1986, Ia afferent excitation of motoneurones in the in vitro new-born rat spinal cord is selectively antagonized by kynurenate, J. Physiol. (London) 370:515–530.Google Scholar
  33. Johnston, D., and Brown, T. H., 1984, Biophysics and microphysiology of synaptic transmission in hippocampus, in: Brain Slices (R. Dingledine, ed.), Plenum Press, New York, pp. 51–86.Google Scholar
  34. Johnston, G. A. R., 1972, Convulsions induced in 10-day-old rats by intraperitoneal injections of monosodium glutamate and related excitant amino acids, Biochem. Pharmacol. 22:137–140.CrossRefGoogle Scholar
  35. Lacey, M. G., and Henderson, G., 1986, Actions of phencyclidine on rat locus coeruleus neurons in vitro, Neuroscience 17:485–494.PubMedCrossRefGoogle Scholar
  36. Little, H. J., and Atkinson, H. D., 1984, Ketamine potentiates the responses of the rat superior cervical ganglion to GABA, Eur. J. Pharmacol. 98:53–59.PubMedCrossRefGoogle Scholar
  37. MacDermott, A. B., Mayer, M. L., Westbrook, G. L., Smith, S. J., and Barker, J. L., 1986, NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones, Nature 321:519–522.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. MacDonald, J. F., 1985, Measurements of transmitter action: The problem of voltage dependence, Can. J. Physiol. Pharmacol. 63:825–830.PubMedCrossRefGoogle Scholar
  40. MacDonald, J. F., Miljkovic, Z., and Pennefather, P., 1987, Use-dependent block of excitatory amino acid currents in cultured hippocampal neurons by ketamine, J. Neurophysiol. 58:251–266.PubMedGoogle Scholar
  41. MacDonald, J. F., and Schneiderman, J. H., 1984, L-Aspartic acid potentiates “slow” inward current in cultured spinal cord neurones, Brain Res. 296:350–355.PubMedCrossRefGoogle Scholar
  42. MacDonald, J. F., and Wojtowicz, J. M., 1982, The effects of L-glutamate and its analogues upon the membrane conductance of central murine neurones in culture, Can. J. Physiol. Pharmacol. 60:282–296.PubMedCrossRefGoogle Scholar
  43. 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 neurons, Brain Res. 237:248–253.PubMedCrossRefGoogle Scholar
  44. MacDonald, J. F., Schneiderman, J. H., and Miljkovic, Z., 1986. Excitatory amino acids and regenerative activity in cultured neurones, in: Excitatory Amino Acids and Epilepsy (R. Schwarcz and Y. Ben Ari, eds.), Plenum Press, New York, pp. 425–438.Google Scholar
  45. Maleque, M. A., Warnick, J. E., and Albuquerque, E. X., 1981, The mechanism and site of action of ketamine on skeletal muscle, J. Pharmacol. Exp. Ther. 219:638–645.PubMedGoogle Scholar
  46. Martin, D., and Lodge, D., 1985, Ketamine acts as a noncompetitive N-methyl-D-aspartate antagonist on frog spinal cord in vitro, Neuropharmacology 24:999–1003.PubMedCrossRefGoogle Scholar
  47. Mayer, M. L., and Westbrook, G. L., 1985, The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture, J. Physiol. (London) 361:65–90.Google Scholar
  48. Mayer, M. L., Westbrook, G. L., and Guthrie, P. B., 1984, Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones, Nature 309:261–263.PubMedCrossRefGoogle Scholar
  49. Meldrum, B. S., Croucher, M. J., Badman, G., and Collins, J. F., 1983, Antiepileptic actions of excitatory amino acid antagonists in the photosensitive baboon, Papio papio, Neurosci. Lett. 39:101–104.PubMedCrossRefGoogle Scholar
  50. Morris, M., Friedlich, J., and MacDonald, J. F., 1986, Intracellular calcium in mammalian brain cells: Fluorescence measurements with Quin2, Exp. Brain Res. 65:520–526.Google Scholar
  51. Mudge, G. H., 1985, Agents affecting volume and composition of body fluids, in: The Pharmacological Basis of Therapeutics, 7th ed. (A. G. Gilman, L. S. Goodman, T. W. Rail, and F. Murad, eds.), Macmillan Co., New York, pp. 846–878.Google Scholar
  52. Neher, E., and Steinbach, J. H., 1978, Local anaesthetics transiently block currents through single acetylcholine- receptor channels, J. Physiol. (London) 277:153–176.Google Scholar
  53. Nelson, P. G., Pun, R. Y. K., and Westbrook, G. L., 1986, Synaptic excitation in cultures of mouse spinal cord neurones: Receptor pharmacology and behavior of synaptic currents, J. Physiol. (London) 372:169–190.Google Scholar
  54. Nistri, A., and Constanti, A., 1979, Pharmacological characterization of different types of GAB A and glutamate receptors in vertebrates and invertebrates, Prog. Neurobiol. 13:117–235.PubMedCrossRefGoogle Scholar
  55. Nowak, L., Bregestovski, P., Ascher, P., Herbert, A., and Prochiantz, A., 1984, Magnesium gates glutamate- activated channels in mouse central neurones, Nature 307:462–465.PubMedCrossRefGoogle Scholar
  56. Puil, E., 1981, S-glutamate: Its interactions with spinal neurons, Brain Res. Rev. 3:229–322.Google Scholar
  57. Riveros, N., and Orrego, F., 1986, N-Methylaspartate-activated calcium channels in rat brain cortex slices: Effect of calcium channel blockers and of inhibitory and depressant substances, Neuroscience 17:541–546.PubMedCrossRefGoogle Scholar
  58. Rucci, F. S., and Caroli, G., 1974, Ketamine and eclampsia, Br. J. Anaesthesiol. 46:546.CrossRefGoogle Scholar
  59. Ryan, G. P., Hackman, J. C., and Davidoff, R. A., 1984, Spinal seizures and excitatory amino acid-mediated synaptic transmission, Neurosci. Lett. 44:161–166.PubMedCrossRefGoogle Scholar
  60. Schneiderman, J. H., 1986, Low concentrations of penicillin rhythmic, synchronous synaptic potentials in hippocampal slice, Brain Res. 398:231–241.PubMedCrossRefGoogle Scholar
  61. Schneiderman, J. H., and Evans, J. C., 1986, Effects of anticonvulsants on penicillin-induced bursts in guinea pig hippocampal slices, Epilepsia 27:347–353.PubMedCrossRefGoogle Scholar
  62. Strichartz, G. R., 1973, The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine, J. Gen. Physiol. 62:37–57.PubMedCrossRefGoogle Scholar
  63. Thomson, A. M., 1986, A magnesium-sensitive post-synaptic potential in rat cerebral cortex resembles neuronal responses to N-methylapartate, J. Physiol. (London) 370:531–549.Google Scholar
  64. Weitz, M. D., Merlob, P., Amir, J., and Reisner, S. H., 1981, A possible role for aspartic acid in neonatal seizures, Arch. Neurol. 38:258–259.PubMedGoogle Scholar
  65. White, P. F., Way, W. L., and Trevor, A. J., 1982, Ketamine: Its pharmacology and therapeutic uses, Anesthesiology 56:119–136.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • J. F. MacDonald
    • 1
  • Z. Miljkovic
    • 1
  • J. H. Schneiderman
    • 2
  1. 1.Playfair Neuroscience UnitUniversity of Toronto, The Toronto HospitalTorontoCanada
  2. 2.Wellesley HospitalTorontoCanada

Personalised recommendations