Molluscan ligand-gated ion-channel receptors

Part of the EXS book series (EXS, volume 63)


In this chapter we introduce the reader to the structures of the different types of ligand-gated ion-channel receptor, and the numerous receptor subtypes that have recently been revealed to exist, in both invertebrate and vertebrate species, by the application of molecular biological methods. We then review some of the data in support of the existence, in molluscs, of such receptor/channel complexes for γ-aminobutyric acid, glutamate and acetylcholine. Finally, recent results from our laboratory on the cloning and expression of complementary DNAs, from the pond-snail Lymnaea stagnalis, that encode GABAA and glutamate receptor subunits will be described.


5HT3 Receptor Receptor Subunit Nicotinic Acetylcholine Receptor Glycine Receptor Chloride Current 
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  1. Azanza, M. J. and Walker, R. J. (1975) GABA-receptor interactions; models in Helix aspersa neurons. Comp. Biochem. Physiol. 50C, 155–161.Google Scholar
  2. Barnard, E. A., Darlison, M. G. and Seeburg, P. (1987) Molecular biology of the GABAA receptor: the receptor/channel superfamily. Trends Neurosci. 10, 502–509.CrossRefGoogle Scholar
  3. Bateson, A. N., Lasham, A. and Darlison, M. G. (1991a) γ-Aminobutyric acidA receptor heterogeneity is increased by alternative splicing of a novel β-subunit gene transcript. J. Neurochem. 56, 1437–1440.CrossRefGoogle Scholar
  4. Bateson, A. N., Harvey, R. J., Wisden, W., Glencorse, T. A., Hicks, A. A., Hunt, S. P., Barnard, E. A. and Darlison, M. G. (1991b) The chicken GABAA receptor αl subunit: cDNA sequence and localization of the corresponding mRNA. Molec. Brain Res. 9, 333–339.CrossRefGoogle Scholar
  5. Bettler, B., Boulter, J., Hermans-Borgmeyer, I., O’Shea-Greenfield, A., Deneris, E. S., Moll, C., Borgmeyer, U., Hollmann, M. and Heinemann, S. (1990) Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron 5, 583–595.CrossRefGoogle Scholar
  6. Blair, L. A. C, Levitan, E. S., Marshall, J., Dionne, V. E. and Barnard, E. A. (1988) Single subunits of the GABAA receptor form ion channels with properties of the native receptor. Science 242, 577–579.CrossRefGoogle Scholar
  7. Bolshakov, V. Y., Gapon, S. A. and Magazanik, L. G. (1991) Different types of glutamate receptors in isolated and identified neurones of the mollusc Planorbarius corneus. J. Physiol. 439, 15–35.Google Scholar
  8. Boulter, J., Hollmann, M., O’Shea-Greenfield, A., Hartley, M., Deneris, E., Maron, C. and Heinemann, S. (1990) Molecular cloning and functional expression of glutamate receptor subunit genes. Science 249, 1033–1037.CrossRefGoogle Scholar
  9. Cooper, E., Couturier, S. and Ballivet, M. (1991) Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptor. Nature 350, 235–238.CrossRefGoogle Scholar
  10. Couturier, S., Bertrand, D., Matter, J.-M., Hernandez, M.-C., Bertrand, S., Millar, N., Valera, S., Barkas, T. and Ballivet, M. (1990) A neuronal nicotinic acetylcholine receptor subunit (α7) is developmentally regulated and forms a homo-oligomeric channel blocked by α-BTX. Neuron 5, 847–856.CrossRefGoogle Scholar
  11. Egebjerg, J., Bettler, B., Hermans-Borgmeyer, I. and Heinemann, S. (1991) Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature 351, 745–748.CrossRefGoogle Scholar
  12. ffrench-Constant, R. H., Mortlock, D. P., Shaffer, C. D., MacIntyre, R. J. and Roush, R. T. (1991) Molecular cloning and transformation of cyclodiene resistance in Drosophila: an invertebrate γ-aminobutyric acid subtype A receptor locus. Proc. Natl Acad. Sci. USA 88, 7209–7213.CrossRefGoogle Scholar
  13. Frohman, M. A. and Martin, G. R. (1989) Rapid amplification of cDNA ends using nested primers. Technique 1, 165–170.Google Scholar
  14. Frohman, M. A., Dush, M. K. and Martin, G. R. (1988) Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc. Natl Acad. Sci. USA 85, 8998–9002.CrossRefGoogle Scholar
  15. Ger, B. A. and Zeimal, E. V. (1977) Pharmacological study of two kinds of cholinoreceptors on the membrane of identified completely isolated neurones of Planorbarius corneus. Brain Res. 121, 131–149.CrossRefGoogle Scholar
  16. Grenningloh, G., Rienitz, A., Schmitt, B., Methfessel, C., Zensen, M., Beyreuther, K., Gundelfinger, E. D. and Betz, H. (1987) The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature 328, 215–220.CrossRefGoogle Scholar
  17. Grenningloh, G., Pribilla, I., Prior, P., Multhaup, G., Beyreuther, K., Taleb, O. and Betz, H. (1990a) Cloning and expression of the 58 kd β subunit of the inhibitory glycine receptor. Neuron 4, 963–970.CrossRefGoogle Scholar
  18. Grenningloh, G., Schmieden, V., Schofield, P. R., Seeburg, P. H., Siddique, T., Mohandas, T. K., Becker, C.-M. and Betz, H. (1990b) Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EM BO J. 9, 771–776.Google Scholar
  19. Harvey, R. J., Vreugdenhil, E., Zaman, S. H., Bhandal, N. S., Usherwood, P. N. R., Barnard, E. A. and Darlison, M. G. (1991) Sequence of a functional invertebrate GABAA receptor subunit which can form a chimeric receptor with a vertebrate α subunit. EM BO J. 10, 3239–3245.Google Scholar
  20. Hermans-Borgmeyer, I., Zopf, D., Ryseck, R.-P., Hovemann, B., Betz, H. and Gundelfinger, E. D. (1986) Primary structure of a developmentally regulated nicotinic acetylcholine receptor protein from Drosophila. EM BO J. 5, 1503–1508.Google Scholar
  21. Hollmann, M., O’Shea-Greenfield, A., Rogers, S. W. and Heinemann, S. (1989) Cloning by functional expression of a member of the glutamate receptor family. Nature 342, 643–648.CrossRefGoogle Scholar
  22. Hutton, M. L., Harvey, R. J., Barnard, E. A. and Darlison, M. G. (1991) Cloning of a cDNA that encodes an invertebrate glutamate receptor subunit. FEBS Lett. 292, 111–114.CrossRefGoogle Scholar
  23. Ikemoto, Y. and Akaike, N. (1988) The glutamate-induced chloride current in Aplysia neurones lacks pharmacological properties seen for excitatory responses to glutamate. Eur. J. Pharmac. 150, 313–318.CrossRefGoogle Scholar
  24. Jonas, P., Baumann, A., Merz, B. and Gundelfinger, E. D. (1990) Structure and developmental expression of the Dα2 gene encoding a novel nicotinic acetylcholine receptor protein of Drosophila melanogaster. FEBS Lett. 269, 264–268.CrossRefGoogle Scholar
  25. Katchman, A. N. and Zeimal, E. V. (1982) Ionic mechanisms of the rapid (nicotinic) phase of acetylcholine response in identified Planobarius corneus neurones. Brain Res. 241, 95–103.Google Scholar
  26. Kehoe, J. (1972a) Ionic mechanisms of a two-component cholinergic inhibition in Aplysia neurones. J. Physiol. 225, 85–114.Google Scholar
  27. Kehoe, J. (1972b) Three acetylcholine receptors in Aplysia neurones. J. Physiol. 225, 115–146.Google Scholar
  28. Kehoe, J., Sealock, R. and Bon, C. (1976) Effects of α-toxins from Bungarus multicinctus and Bungarus caeruleus on cholinergic responses in Aplysia neurones. Brain Res. 107, 527–540.CrossRefGoogle Scholar
  29. Keinänen, K., Wisden, W., Sommer, B., Werner, P., Herb, A., Verdoorn, T. A., Sakmann, B. and Seeburg, P. H. (1990) A family of AMPA-selective glutamate receptors. Science 249, 556–560.CrossRefGoogle Scholar
  30. King, W. M. and Carpenter, D. O. (1987) Distinct GABA and glutamate receptors may share a common channel in Aplysia neurons. Neurosci. Lett. 82, 343–348.CrossRefGoogle Scholar
  31. King, W. M. and Carpenter, D. O. (1989) Voltage-clamp characterization of CI conductance gated by GABA and L-glutamate in single neurons of Aplysia. J. Neurophysiol. 61, 892–899.Google Scholar
  32. Kuhse, J., Schmieden, V. and Betz, H. (1990) Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor. J. Biol. Chem. 265, 22317–22320.Google Scholar
  33. Kuhse, J., Kuryatov, A., Maulet, Y., Malosio, M. L., Schmieden, V. and Betz, H. (1991) Alternative splicing generates two isoforms of the α2 subunit of the inhibitory glycine receptor. FEBS Lett. 283, 73–77.CrossRefGoogle Scholar
  34. Lüddens, H., Pritchett, D. B., Köhler, M., Killisch, I., Keinänen, K., Monyer, H., Sprengel, R. and Seeburg, P. H. (1990) Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Nature 346, 648–651.CrossRefGoogle Scholar
  35. Malosio, M.-L., Marqueze-Pouey, B., Kuhse, J. and Betz, H. (1991a) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EM BO J. 10, 2401–2409.Google Scholar
  36. Malosio, M.-L., Grenningloh, G., Kuhse, J., Schmieden, V., Schmitt, B., Prior, P. and Betz, H. (1991b) Alternative splicing generates two variants of the α1 subunit of the inhibitory glycine receptor. J. Biol. Chem. 266, 2048–2053.Google Scholar
  37. Maricq, A. V., Peterson, A. S., Brake, A. J., Myers, R. M. and Julius, D. (1991) Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 254, 432–437.CrossRefGoogle Scholar
  38. Marshall, J., Buckingham, S. D., Shingai, R., Lunt, G. G., Goosey, M. W., Darlison, M. G., Sattelle, D. B. and Barnard, E. A. (1990) Sequence and functional expression of a single α subunit of an insect nicotinic acetylcholine receptor. EM BO J. 9, 4391–4398.Google Scholar
  39. Mishina, M., Takai, T., Imoto, K., Noda, M., Takahashi, T., Numa, S., Methfessel, C. and Sakmann, B. (1986) Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature 321, 406–411.CrossRefGoogle Scholar
  40. Moriyoshi, K., Masu, M., Ishii, T., Shigemoto, R., Mizuno, N. and Nakanishi, S. (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354, 31–37.CrossRefGoogle Scholar
  41. Morris, B. J., Hicks, A. A., Wisden, W., Darlison, M. G., Hunt, S. P. and Barnard, E. A. (1990) Distinct regional expression of nicotinic acetylcholine receptor genes in chick brain. Molec. Brain Res. 7, 305–315.CrossRefGoogle Scholar
  42. Noda, M., Takahashi, H., Tanabe, T., Toyosato, M., Furutani, Y., Hirose, T., Asai, M., Inayama, S., Miyata, T. and Numa, S. (1982) Primary structure of α-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature 299, 793–797.CrossRefGoogle Scholar
  43. Olsen, R. W. and Tobin, A. J. (1990) Molecular biology of GABAA receptors. FASEB J. 4, 1469–1480.Google Scholar
  44. Oyama, Y., Ikemoto, Y., Kits, K. S. and Akaike, N. (1990) GABA affects the glutamate receptor-chloride channel complex in mechanically isolated and internally perfused Aplysia neurons. Eur. J. Pharmac. 185, 43–52.CrossRefGoogle Scholar
  45. Piggott, S. M., Kerkut, G. A. and Walker, R. J. (1977) The actions of Picrotoxin, strychnine, bicuculline and other convulsants and antagonists on the responses to acetylcholine glutamic acid and gamma-aminobutyric acid on Helix neurones. Comp. Biochem. Physiol. 57C, 107–116.Google Scholar
  46. Popot, J.-L. and Changeux, J.-P. (1984) Nicotinic receptor of acetylcholine: structure of an oligomeric integral membrane protein. Physiol. Rev. 64, 1162–1239.Google Scholar
  47. Pritchett, D. B., Lüddens, H. and Seeburg, P. H. (1989) Type I and type II GABAA-benzodiazepine receptors produced in transfected cells. Science 245, 1389–1392.CrossRefGoogle Scholar
  48. Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B. and Erlich, H. A. (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239, 487–491.CrossRefGoogle Scholar
  49. Sawruk, E., Schloss, P., Betz, H. and Schmitt, B. (1990a) Heterogeneity of Drosophila nicotinic acetylcholine receptors: SAD, a novel developmentally regulated α-subunit. EM BO J. 9, 2671–2677.Google Scholar
  50. Sawruk, E., Udri, C., Betz, H. and Schmitt, B. (1990b) SBD, a novel structural subunit of the Drosophila nicotinic acetylcholine receptor, shares its genomic localization with two α-subunits. FEBS Lett. 273, 177–181.CrossRefGoogle Scholar
  51. Schoepfer, R., Conroy, W. G., Whiting, P., Gore, M. and Lindstrom, J. (1990) Brain α-bungarotoxin binding protein cDNAs and MAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily. Neuron 5, 35–48.CrossRefGoogle Scholar
  52. Schofield, P. R., Darlison, M. G., Fujita, N., Burt, D. R., Stephenson, F. A., Rodriguez, H., Rhee, L. M., Ramachandran, J., Reale, V., Glencorse, T. A., Seeburg, P. H. and Barnard, E. A. (1987) Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family. Nature 328, 221–227.CrossRefGoogle Scholar
  53. Schuster, C. M., Ultsch, A., Schloss, P., Cox, J. A., Schmitt, B. and Betz, H. (1991) Molecular cloning of an invertebrate glutamate receptor subunit expressed in Drosophila muscle. Science 254, 112–114.CrossRefGoogle Scholar
  54. Sigel, E., Baur, R., Malherbe, P. and Möhler, H. (1989) The rat β1-subunit of the GABAA receptor forms a picrotoxin-sensitive anion channel open in the absence of GABA. FEBS Lett. 257, 377–379.CrossRefGoogle Scholar
  55. Sigel, E., Baur, R., Trübe, G., Möhler, H. and Malherbe, P. (1990) The effect of subunit composition of rat brain GABAA receptors on channel function. Neuron 5, 703–711.CrossRefGoogle Scholar
  56. Sommer, B., Keinänen, K., Verdoorn, T. A., Wisden, W., Burnashev, N., Herb, A., Köhler, M., Takagi, T., Sakmann, B. and Seeburg, P. H. (1990) Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science 249, 1580–1585.CrossRefGoogle Scholar
  57. Vehovszky, A., Bokisch, A. J., Krogsgaard-Larsen, P. and Walker, R. J. (1989) Pharmacological profile of gamma-aminobutyric acid (GABA) receptors of identified central neurones from Helix aspersa. Comp. Biochem. Physiol. 92C, 391–399.CrossRefGoogle Scholar
  58. Verdoorn, T. A., Burnashev, N., Monyer, H., Seeburg, P. H. and Sakmann, B. (1991) Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252, 1715–1718.CrossRefGoogle Scholar
  59. Werner, P., Voigt, M., Keinanen, K., Wisden, W. and Seeburg, P. H. (1991) Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature 351, 742–744.CrossRefGoogle Scholar
  60. Whiting, P., McKernan, R. M. and Iversen, L. L. (1990) Another mechanism for creating diversity in γ-aminobutyrate type A receptors: RNA splicing directs expression of two forms of γ2 subunit, one of which contains a protein kinase C phosphorylation site. Proc. Natl Acad. Scl. USA 87, 9966–9970.CrossRefGoogle Scholar
  61. Wilson-Shaw, D., Robinson, M., Gambarana, C., Siegel, R. E. and Sikela, J. M. (1991) A novel γ subunit of the GABAA receptor identified using the polymerase chain reaction. FEBS Lett. 284, 211–215.CrossRefGoogle Scholar
  62. Wisden, W., Morris, B. J., Darlison, M. G., Hunt, S. P. and Barnard, E. A. (1988) Distinct GABAA receptor α subunit mRNAs show differential patterns of expression in bovine brain. Neuron 1, 937–947.CrossRefGoogle Scholar
  63. Yarowsky, P. J. and Carpenter, D. O. (1976) Aspartate: distinct receptors on Aplysia neurons. Science 192, 807–809.CrossRefGoogle Scholar
  64. Yarowsky, P. J. and Carpenter, D. O. (1978a) Receptors for gamma-aminobutyric acid (GABA) on Aplysia neurons. Brain Res. 144, 75–94.CrossRefGoogle Scholar
  65. Yarowsky, P. J. and Carpenter, D. O. (1978b) A comparison of similar ionic responses to γ-aminobutyric acid and acetylcholine. J. Neurophysiol. 41, 531–541.Google Scholar
  66. Yongsiri, A., Funase, K., Takeuchi, H., Shimamoto, K. and Ohfune, Y. (1988) Classification of GABA receptors in snail neurones. Eur. J. Pharmac. 155, 239–245.CrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 1993

Authors and Affiliations

  1. 1.Institut für Zellbiochemie und klinische Neurobiologie, Universitäts-Krankenhaus EppendorfUniversität HamburgHamburg 20Germany
  2. 2.MRC Molecular Neurobiology UnitMRC CentreCambridgeEngland

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