Modulation of Ionic Currents by Metabotropic Glutamate Receptors in the CNS

  • Urs Gerber
  • Beat H. Gähwiler
Chapter
Part of the The Receptors book series (REC)

Abstract

Stimulation of neuronal metabotropic glutamate receptors (mGluRs) activates G-proteins initiating a multitude of intracellular processes. Electrophysiological observations indicate that ion channels are among the substrates for the intracellular messengers dispatched by activated mGluRs, thus modulating the electrical behavior of neurons owing to their coupling to numerous membrane ionic conductances. In some of the first experiments to demonstrate metabotropic effects of glutamate, electrophysiological techniques were employed using transfected oocytes to assay for changes in second-messenger levels in response to glutamate (Sugiyama et al., 1987, 1989). It has only recently been shown that activation of mGluRs can also modify the firing properties of neurons (Stratton et al., 1989, 1990; Baskys et al., 1990; Charpak et al., 1990; Desai and Conn, 1991).

Keywords

Calcium Current Potassium Current Mossy Fiber Metabotropic Glutamate Receptor Cerebellar Granule Cell 
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References

  1. Akaike, N., Shirasaki, T., and Harata, N. (1991) Metabotropic glutamate receptors activates the potassium conductance in freshly dissociated hippocampal CA1 neurons. Soc. Neurosci. 17, 255.Google Scholar
  2. Aniksztejn, L., Otani, S., and Ben-ari, Y. (1992) Quisqualate metabotropic receptors modulate NMDA currents and facilitate induction of long-term potentiation through protein kinase C. Eur. J. Neurosci. 4, 500–505.PubMedCrossRefGoogle Scholar
  3. Anwyl, R. (1992) Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Rev. Neurosci. 3, 217–231.PubMedGoogle Scholar
  4. Baraban, J. M., Snyder, S. H., and Alger, B. E. (1985) Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons, Electrophysiological effects of phorbol esters. Proc. Natl. Acad. Sci. USA 82, 2538–2542.PubMedCrossRefGoogle Scholar
  5. Bashir, Z. I., Bortolotto, Z. A., Davies, C. H., Berretta, N., Irving, A. J., Seal, A. J., Henley, J. M., Jane, D. E., Watkins, J. C., and Collingridge, G. L. (1993) Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature 363, 347–350.PubMedCrossRefGoogle Scholar
  6. Baskys, A. (1992) Metabotropic receptors and “slow” excitatory actions of glutamate agonists in the hippocampus. TINS 15, 92–96.PubMedGoogle Scholar
  7. Baskys, A., Bernstein, N. K., Barolet, A. W., and Carlen, P. L. (1990) NMDA and quisqualate reduce a Ca-dependent K’ current by a protein kinase-mediated mechanism. Neurosci. Lett. 112, 76–81.PubMedCrossRefGoogle Scholar
  8. Bleakman, D., Rusin, K. I., Chard, P. S., Glaum, S. R., and Miller, R. J. (1992) Metabotropic glutamate receptors potentiate ionotropic glutamate responses in the rat dorsal horn. Mol. Pharmacol. 42, 192–196.PubMedGoogle Scholar
  9. Bockaert, J. (1991) G proteins and G-protein-coupled receptors: structure, function and interactions. Curr. Opinion Neurobiol. 1, 32–42.CrossRefGoogle Scholar
  10. Bossu, J. L., Fagni, L., Nooney, J., and Feltz, A. (1992) Increased Ca channel activity due to metabotropic glutamate receptor stimulation in isolated rat cerebellar granule cells. J. Physiol. 459, 250 P.Google Scholar
  11. Bossu, J. L., Nooney, J. M., Chavis, P., Fagni, L., Bockaert, J., and Feltz, A. (1993) Facilitatory effect on L-type Ca channels of glutamate metabotropic receptors in rodent cerebellar granule cells. J. Neurochem. 61, S197B.Google Scholar
  12. Brown, D. A. and Adams, P. R. (1980) Muscarinic suppression of a novel voltage-sensitive K’-current in a vertebrate neuron. Nature 283, 673–676.PubMedCrossRefGoogle Scholar
  13. Caeser, M., Brown, D. A., Gähwiler, B. H., and Knöpfel, T. (1993) Characterization of a calcium-dependent current generating a slow after depolarization of CA3 pyramidal cells in rat hippocampal slice cultures. Eur. J. Neurosci. 5, 560–569.PubMedCrossRefGoogle Scholar
  14. Cerne, R. and Randic, M. (1992) Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid. Neurosci. Lett. 144, 180–184.PubMedCrossRefGoogle Scholar
  15. Charpak, S. and Gähwiler, B. H. (1991) Glutamate mediates a slow synaptic response in hippocampal slice cultures. Proc. R. Soc. Lond. (Biol.) 243, 221–226.CrossRefGoogle Scholar
  16. Charpak, S., Gähwiler, B. H., Do, K. Q., and Knöpfel, T. (1990) Potassium conductances in hippocampal neurons blocked by excitatory amino acid transmitters. Nature 347, 765–767.PubMedCrossRefGoogle Scholar
  17. Chavis, P., Fagni, L., and Bockaert, J. (1993) Metabotropic glutamate receptors inhibit L-type calcium channels in cultured cerebellar granule cells. J. Neurochem. 61, SI5C.Google Scholar
  18. Colino, A. and Halliwell, J. V. (1993) Carbachol potentiates Q current and activates a calcium-dependent non-specific conductance in rat hippocampus in vitro. Eur. J. Neurosci. 5, 1198–1209.PubMedCrossRefGoogle Scholar
  19. Collins, G. G. S. (1993) Actions of agonists of metabotropic glutamate receptors on synaptic transmission and transmitter release in the olfactory cortex. Br. J. Pharmacol. 108, 422–430.PubMedCrossRefGoogle Scholar
  20. Conn, P. J. and Desai, M. A. (1991) Pharmacology and physiology of metabotropic glutamate receptors in mammalian central nervous system. Drug Dey. Res. 24, 207–229.CrossRefGoogle Scholar
  21. Constanti, A. and Libri, V. (1992) Trans-ACPD induces a slow post-stimulus inward tail current (IADP) in guinea-pig olfactory cortex neurones. Eur. J. Pharmacol. 214, 105–106.CrossRefGoogle Scholar
  22. Crépel, F., Daniel, H., Hemart, N., and Jaillard, D. (1991) Effects of ACPD and AP3 on parallel-fibre-mediated EPSPs of Purkinje cells in cerebellar slices in vitro. Exp. Brain Res. 86, 402–406.PubMedCrossRefGoogle Scholar
  23. Desai, M. A. and Conn, P. J. (1990) Selective activation of phosphoinositide hydrolysis by a rigid analogue of glutamate. Neurosci. Lett. 109, 157–162.PubMedCrossRefGoogle Scholar
  24. Desai, M. A., Smith, T. S., and Conn, P. J. (1991) Excitatory effects of ACPD receptor activation in the hippocampus are mediated by direct effects on pyramidal cells and blockade of synaptic inhibition. J. Neurophysiol. 66, 40–52.PubMedGoogle Scholar
  25. Desai, M. A. and Conn, P. J. (1992) Multiple metabotropic glutamate receptors regulate hippocampal function. Synapse 12, 206–213.PubMedCrossRefGoogle Scholar
  26. East, S. J. and Garthwaite, J. (1992) Actions of a metabotropic glutamate receptor agonist in immature and adult cerebellum. Eur. J. Pharmacol. 219, 395–400.PubMedCrossRefGoogle Scholar
  27. Eaton, S. A., Jane, D. E., Jones, P. L., St., J., Porter, R. H. P., Pook, P. C. K., Sunter, D. C., Udvarhelyi, P. M., Roberts, P. J., Salt, T. E., and Watkins, J. C. (1993) Competitive antagonism at metabotropic glutamate receptors by S-4-carboxyphenylglycine and RS-a-methyl-4-carboxyphenylglycine. Eur. J. Pharmacol. 244, 195–197.PubMedCrossRefGoogle Scholar
  28. Fagni, L., Bossu, J. L., and Bockaert, J. (1991) Activation of a large-conductance Cat+-dependent K’ channel by stimulation of glutamate phosphoinositide-coupled receptors in cultured cerebellar granule cells. Eur. J. Neurosci. 3, 778–789.PubMedCrossRefGoogle Scholar
  29. Fagni, L., Chavis, P., Bossu, J. L., Nooney, J. M., Feltz, A., and Bockaert, J. (1993) Control of ionic channels by metabotropic glutamate receptors. J. Neurochem. 61, S198A.Google Scholar
  30. Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R., and Bourne, H. R. (1992) Hormonal stimulation of adenylyl cyclase through Gi-protein 3y subunits. Nature 356, 159–161.PubMedCrossRefGoogle Scholar
  31. Gerber, U., Lüthi, A., and Gähwiler, B. H. (1993) Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells. Proc. R. Soc. Lond. (Biol.) 254, 169–172.CrossRefGoogle Scholar
  32. Gerber, U., Sim, J. A., and Gähwiler, B. H. (1992) Reduction of potassium conductances mediated by metabotropic glutamate receptors in rat CA3 pyramidal cells does not require protein kinase C or protein kinase A. Eur. J. Neurosci. 4, 792–797.PubMedCrossRefGoogle Scholar
  33. Gilman, A. G. (1987) G proteins, transducers of receptor-generated signals. Annu. Rev. Biochem. 56, 615–649.PubMedCrossRefGoogle Scholar
  34. Glaum, S. R. and Miller, R. J. (1992) Metabotropic glutamate receptors mediate excitatory transmission in the nucleus of the solitary tract. J. Neurosci. 12, 2251–2258.PubMedGoogle Scholar
  35. Glaum, S. R., Slater, N. T., Rossi, D. J., and Miller, R. J. (1992) Role of metabotropic glutamate ACPD) receptors at the parallel fiber-Purkinje cell synapse. J. Neurophysiol. 68, 1453–1461.PubMedGoogle Scholar
  36. Greene, C., Schwindt, P., and Crill, W. (1992) Metabotropic receptor mediated after depolarization in neocortical neurons. Eur. J. Pharmacol. 226, 279–280.PubMedCrossRefGoogle Scholar
  37. Guérineau, N. C., Gähwiler, B. H., and Gerber, U. (1994) G-proteins mediate reduction of resting K+ current by metabotropic glutamate and muscarinic receptors in rat CA3 cells. J. Physiol. 474, 27–33.PubMedGoogle Scholar
  38. Halliwell, J. V. and Adams, P. R. (1982) Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 250, 71–92.PubMedCrossRefGoogle Scholar
  39. Harvey, J. and Collingridge, G. L. (1993) Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R-ACPD in rat hippocampal slices. Br. J. Pharmacol. 109, 1085–1090.PubMedCrossRefGoogle Scholar
  40. Hu, G.-Y. and Storm, J. F. (1992) Excitatory amino acids acting on metabotropic glutamate receptors broaden the action potential in hippocampal neurons. Brain Res. 568, 339–344.CrossRefGoogle Scholar
  41. Inoue, T., Miyakawa, H., Ito, K., Mikoshiba, K., and Kato, H. (1992) A hyperpolarizing response induced by glutamate in mouse cerebellar Purkinje cells. Neurosci. Res. 15, 265–271.PubMedCrossRefGoogle Scholar
  42. Irving, A. J., Schofield, J. G., Watkins, J. C., Sunter, D. C., and Collingridge, G. L. (1990)1 S,3R-ACPD stimulates and L-AP3 blocks Cat+ mobilization in rat cerebellar neurons. Eur. J. Pharmacol. 186, 363–365.Google Scholar
  43. Ito, M. and Karachot, L. (1990) Messengers mediating long-term desensitization in cerebellar Purkinje cells. NeuroReport 1, 129–132.Google Scholar
  44. Jan, L. Y. and Jan, Y. N. (1992) Tracing the roots of ion channels. Cell 69, 715–718.PubMedCrossRefGoogle Scholar
  45. Kaczmarek, L. K. and Levitan, I. B. (1987) Neuromodulation: The Biochemical Control of Neuronal Excitability (Oxford University Press, Oxford, UK).Google Scholar
  46. Katada, T. and Ui, M. (1982) Direct modification of the membrane adenylyl cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc. Natl. Acad. Sci. USA 79, 3129–3133.PubMedCrossRefGoogle Scholar
  47. Kinney, G. A. and Slater, N. T. (1992) Potentiation of mossy fiber-evoked EPSPs in turtle cerebellar Purkinje cells by the metabotropic glutamate receptor agonist 1S,3R-ACPD. J. Neurophysiol. 67, 1006–1008.PubMedGoogle Scholar
  48. Kubo, Y., Reuveny, E., Slesinger, P. A., Jan, Y. N., and Jan, L. Y. (1993) Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel. Nature 364, 802–806.PubMedCrossRefGoogle Scholar
  49. Lancaster, B., and Adams, P. R. (1986) Calcium-dependent current generating the after hyperpolarization of hippocampal neurons. J. Neurophysiol. 55, 1268–1282.PubMedGoogle Scholar
  50. Lancaster, B., Nicoll, R. A., and Perkel, D. J. (1991) Calcium activates two types of potassium channels in rat hippocampal neurons in culture. J. Neurosci. 11, 23–30.PubMedGoogle Scholar
  51. Lester, R. A. J. and Jahr, C. E. (1990) Quisqualate receptor-mediated depression of calcium currents in hippocampal neurons. Neuron 4, 741–749.PubMedCrossRefGoogle Scholar
  52. Lüthi, A., Gähwiler, B. H., and Gerber, U. (1993) Interaction between ionotropic and metabotropic glutamate receptors in the hippocampus. Experientia 49, A74.Google Scholar
  53. Madison, D. V. and Nicoll, R. A. (1986) Cyclic adenosine 3’,5’-monophosphate mediates -receptor actions of noradrenaline in rat hippocampal pyramidal cells. J. Physiol. (Lond.) 372, 245–259.Google Scholar
  54. Malenka, R. C., Madison, D. V., Andrade, R., and Nicoll, R. A. (1986) Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons. J. Neurosci. 6, 475–480.PubMedGoogle Scholar
  55. Manzoni, O., Fagni, L., Pin, J.-P., Rassendren, F., Poulat, F., Sladeczek, F., and Bockaert, J. (1990) (trans)-1-amino-cyclopentyl-1,3-dicarboxylate stimulates quisqualate phosphoinositide-coupled receptors but not ionotropic glutamate receptors in striatal neurons and Xenopus oocytes. Mol. Pharmacol. 38, 1–6.Google Scholar
  56. Masu, M., Tanable, Y., Tsuchida, K., Shigemoto, R., and Nakanishi, S. (1991) Sequence and expression of a metabotropic glutamate receptor. Nature 349, 760–765.PubMedCrossRefGoogle Scholar
  57. McCormick, D. A. (1991) Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus. J. Neurosci. 12, 278–289.Google Scholar
  58. McCormick, D. A. and von Krosigk, M. (1992) Corticothalamic activation modulates thalamic firing through glutamate “metabotropic” receptors. Proc. Natl. Acad. Sci. USA 89, 2774–2778.PubMedCrossRefGoogle Scholar
  59. Miles, R. and Poncer, J.-C. (1993) Metabotropic glutamate receptors mediate a posttetanic excitation of guinea-pig hippocampal inhibitory neurones. J. Physiol. Lond. 463, 461–473.PubMedGoogle Scholar
  60. Miller, R. J. (1991) Metabotropic excitatory amino acid receptors reveal their true colors. TiPS 146, 365–367.Google Scholar
  61. Müller, W., Petrozzino, J. J., Griffith, L. C., Dahno, W., and Connor, J. A. (1992) Specific involvement of Ca2+-calmodulin kinase II in cholinergic modulation of neuronal responsiveness. J. Neurophysiol. 68, 2264–2269.PubMedGoogle Scholar
  62. Nakanishi, S. (1992) Molecular diversity of glutamate receptors and implications for brain function. Science 258, 597–603.PubMedCrossRefGoogle Scholar
  63. Palmer, E., Monaghan, D. T., and Cotman, C. W. (1989) Trans-ACPD, a selective agonist of the phosphoinositide-coupled excitatory amino acid receptor. Eur. J. Pharmacol. 166, 585–587.PubMedCrossRefGoogle Scholar
  64. Rüegg, U. T. and Burgess, G. M. (1989) Staurosporine, K-252 and UCN-01, potent but nonspecific inhibitors of protein kinases. TiPS 10, 218–220.PubMedGoogle Scholar
  65. Sahara, Y. and Westbrook G. L. (1993) Modulation of calcium currents by a metabotropic glutamate receptor involves fast and slow kinetic components in cultured hippocampal neurons. J. Neurosci. 13, 3041–3050.PubMedGoogle Scholar
  66. Sayer, R. J., Schwindt, P.C., and Crill, W. E. (1992) Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons. J. Neurophysiol 68, 833–842.PubMedGoogle Scholar
  67. Schoepp, D., Bockaert, J., and Sladeczek, F. (1990) Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors. TiPS 11, 508–515.PubMedGoogle Scholar
  68. Schoepp, D. D. and Conn, P. J. (1993) Metabotropic glutamate receptors in brain function and pathology. TiPS 14, 13–20.PubMedGoogle Scholar
  69. Schwartz, E. A. (1993) L-glutamate conditionally modulates the K. current of Müller glial cells. Neuron 10, 1141–1149.PubMedCrossRefGoogle Scholar
  70. Staub, C., Vranesic, I., and Knöpfel, T. (1992) Responses to metabotropic glutamate receptor activation in cerebellar Purkinje cells: induction of an inward current. Eur. J. Neurosci. 4, 832–839.PubMedCrossRefGoogle Scholar
  71. Sternweis, P. C. and Smrcka, A. V. (1992) Regulation of phospholipase C by G proteins. TIBS 17, 502–506.PubMedGoogle Scholar
  72. Stratton, K. R., Worley, P. F., and Baraban, J. M. (1989) Excitation of hippocampal neurons by stimulation of glutamate Qp receptors. Eur. J. Pharmacol. 173, 235–237.PubMedCrossRefGoogle Scholar
  73. Stratton, K. R., Worley, P. F., and Baraban, J. M. (1990) Pharmacological characterization of phosphoinositide-linked glutamate receptor excitation of hippocampal neurons. Eur. J. Pharmacol. 186, 357–361.PubMedCrossRefGoogle Scholar
  74. Sugiyama, H., Ito, I., and Hirono, C. (1987) A new type of glutamate receptor linked to inositol phospholipid metabolism. Nature 325, 531–533.PubMedCrossRefGoogle Scholar
  75. Sugiyama, H., Ito, I., and Watanabe, M. (1989) Glutamate receptor subtypes may be classified into two major categories, A study on Xenopus oocytes injected with rat brain mRNA. Neuron 3, 129–132.PubMedCrossRefGoogle Scholar
  76. Swartz, K. J. and Bean, B. P. (1992) Inhibition of calcium channels in rat CA3 pyramidal neurons by a metabotropic glutamate receptor. J. Neurosci. 12, 4358–4371.PubMedGoogle Scholar
  77. Takagi, H., Takimizu, H., Yoshioka, T., Suzuki, N., and Kudo, Y. (1992) Delayed appearance of a G-protein coupled signal transduction system in cerebellar Purkinje cell dendrites. Neurosci. Res. 15, 206–212.PubMedCrossRefGoogle Scholar
  78. Tang, W.-J. and Gilman, A. G. (1991) Type-specific regulation of adenylyl cyclase by G-protein ßy subunits. Science 254, 1500–1503.PubMedCrossRefGoogle Scholar
  79. Trombley, P. Q. and Westbrook, G. L. (1992) L-AP4 inhibits calcium currents and synaptic transmission via a G-protein-coupled glutamate receptor. J. Neurosci. 12, 2043–2050.PubMedGoogle Scholar
  80. Trussell, L. O. and Jackson, M. B. (1987) Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons. J. Neurosci. 7, 3306–3316.PubMedGoogle Scholar
  81. Vranesic, I., Batchelor, A., Gähwiler, B. H., Garthwaite, J., Staub, C., and Knöpfel, T. (1991) Trans-ACPD-induced Ca2+ signals in cerebellar Purkinje cells. NeuroReport 2, 759–762.Google Scholar
  82. Vranesic, I., Staub, C., and Knöpfel, T. (1993) Activation of metabotropic glutamate receptors induces an outward current which is potentiated by methylxanthines in rat cerebellar Purkinje cells. Neurosci. Res. 16, 209–215.PubMedCrossRefGoogle Scholar
  83. Wang, Z. and McCormick, D. A. (1993) Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R-ACPD. J. Neurosci. 13, 2199–2216.PubMedGoogle Scholar
  84. Yatani, A., Codina, J., Imoto, Y., Reeves, J. P., Birnbaumer, L., and Brown, A. M. (1987) A G-protein directly regulates mammalian cardiac calcium channels. Science 238, 1288–1292.PubMedCrossRefGoogle Scholar
  85. Yool, A. J., Krieger, R. M., and Gruol, D. L. (1992) Multiple ionic mechanisms are activated by the potent agonist quisqualate in cultured cerebellar Purkinje neurons. Brain Res. 573, 83–94.PubMedCrossRefGoogle Scholar
  86. Zegarra-Moran, O., and Moran, O. (1993) Modulation of voltage-dependent calcium channels by glutamate in rat cerebellar granule cells. Exp. Brain Res. 95, 65–69.PubMedCrossRefGoogle Scholar
  87. Zheng, F. and Gallagher, J. P. (1991) Trans-ACPD (trans-D,L-1-amino-1,3cyclopentanedicarboxylic acid) elicited oscillation of membrane potentials in rat dorsolateral septal nucleus neurons recorded intracellularly in vitro. Neurosci. Lett. 125, 147–150.Google Scholar
  88. Zheng, F. and Gallagher, J. P. (1992a) Metabotropic glutamate receptor agonists potentiate a slow after hyperpolarization in CNS neurons. NeuroReport 3, 622–624.Google Scholar
  89. Zheng, F. and Gallagher, J. P. (1992b) Burst firing of rat septal neurons by 1S,3R-ACPD requires influx of extracellular calcium. Eur. J. Pharmacol. 211, 281–282.PubMedCrossRefGoogle Scholar
  90. Zorumski, C. F. and Thio, L. L. (1992) Properties of vertebrate glutamate receptors: calcium mobilization and desensitization. Prog. Neurobiol. 39, 295–336.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Urs Gerber
  • Beat H. Gähwiler

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