Common Structural Principles of Ion Channel Proteins

  • Alfred Maelicke
Conference paper
Part of the NATO ASI Series book series (volume 32)


Hydropathy profiles of the available sequences of ion channel proteins (Fig. 1) suggest that ligand-gated and voltage-gated channels each form a structural family. Ligand-gated channel proteins consist of several subunits a combination of which must be inserted into the membrane to provide ligand-gated conductance (Mishina et al., 1984). In contrast, functional voltage-gated sodium channels are already obtained when only the large subunit is expressed (Noda et al., 1986).


Acetylcholine Receptor Nicotinic Acetylcholine Receptor Gaba Receptor Glycine Receptor Putative Transmembrane Domain 
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. Barkas T, Mauron A, Roth B, Alliod C, Tzartos SJ, Ballivet M (1987) Mapping the main immunogenic region and toxin-binding site of the nicotinic acetylcholine receptor. Science 235: 77–80PubMedCrossRefGoogle Scholar
  2. Barnard EA, Darlison MG, Seeburg P (1987) Molecular biology of the GABAa receptor: the receptor/channel superfamily. Trends Neurosci 10: 502–509CrossRefGoogle Scholar
  3. Baumann A, Krah-Jentgens I, Müller R, Muller-Holtkamp F, Seidel R, Kecskemethy N, Casal J, Ferrus A, Pongs O (1987) Molecular organization of the maternal effect region of the Shaker complex of Drosophila: charakterization of an IA channel transcript with homology to vertebrate Na+ channel. EMBO J 6: 3419–3429PubMedGoogle Scholar
  4. Betz H (1987) Biology and structure of the mammalian glycine receptor. Trends Neurosci 10: 113–117CrossRefGoogle Scholar
  5. Bormann J, Hamill OP, Sakmann B (1987) Mechanism of anion permeation through channels gated by glycine and -y-amino- butyric acid in mouse cultured spinal neurones. J Physiol 385: 243–286PubMedGoogle Scholar
  6. Deisenhofer J, Michel H, Huber R (1985) The structural basis of photosynthetic light reactions in bacteria. Trends Biol Sci 10: 243–248CrossRefGoogle Scholar
  7. Finer-Moore J, Stroud RM (1984) Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor. Proc Natl Acad Sci USA 81: 155–159PubMedCrossRefGoogle Scholar
  8. Giraudat J, Dennis M, Heidmann T, Chang J-Y, Changeux J-P (1986) Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: Serine-262 of the δ subunit is labeled by [3H]chlorpromazine. Proc Natl Acad Sci USA 83: 2719–2723PubMedCrossRefGoogle Scholar
  9. Grenningloh A, Rienitz A, Schmitt B, Methfessel C, Zensen M, Beyreuther K, Gundelfinger ED, Betz H (1987) The strych- nine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature 328: 215–220PubMedCrossRefGoogle Scholar
  10. Hamill OP, Bormann J, Sakmann B (1983) Activation of multiple- conductance state chloride channels in spinal neurones by glycine and GABA. Nature 305: 805–808PubMedCrossRefGoogle Scholar
  11. Imoto K, Methfessel C, Sakmann B, Mishina M, Mori Y, Konno T, Fukuda K, Kurasaki M, Bujo H, Fujita Y, Numa S. (1986) Location of a δ-subunit region determining ion transport through the acetylcholine receptor channel. Nature 324: 670–674PubMedCrossRefGoogle Scholar
  12. Karlin A, Kao PN, DiPaola M (1986) Molecular pharmacology of the nicotinic acetylcholine receptor. Trends Pharmacol Sci 7: 304–308CrossRefGoogle Scholar
  13. Kosower EM (1987) A structural and dynamic model for the nicotinic acetylcholine receptor. Eur J Biochem 168: 431–449PubMedCrossRefGoogle Scholar
  14. Kubo, T., Fukuda, K., Mikami, A., Maeda, A., Takahashi, H., Mishina, M., Haga, T., Haga, K., Ichiyama, A., Kangawa, K., Kojima, M., Matsuo, H., Hirose, T. & Numa, S. (1986) Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature 323: 411–416PubMedCrossRefGoogle Scholar
  15. Kyte J, Doolittle RJ (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157: 105–132PubMedCrossRefGoogle Scholar
  16. Langosch D, Grenningloh G, Schmieden V, Prior P, Malosio M-L, Schmitt B, Betz H (1989) The postsynaptic glycine receptor — a member of the neurotransmitter-gated channel protein family. This volume, pp. 125–130Google Scholar
  17. Lefkowitz RJ, Benovic JL, Kobilka B, Caron MG (1986) β-Adrenergic receptors and rhodopsin: shedding new light on an old subject. Trends Pharmacol Sci 7: 444–448CrossRefGoogle Scholar
  18. Lindstrom J (1986) Probing nicotinic acetylcholine receptors with monoclonal antibodies. Trends Neuro Sci 9: 401–407CrossRefGoogle Scholar
  19. Maelicke A (1988) In: Whittaker VP (ed) Structure and Function of the Nicotinic Acetylcholine Receptor. Springer, Berlin Heidelberg New York, pp 267–313Google Scholar
  20. Maelicke A, Plümer-Wilk R, Fels G, Spencer SR, Engelhard M, Veltel D, Conti-Tronconi BM (1989) Epitope mapping employing antibodies raised against short synthetic peptides: A study of the nicotinic acetylcholine receptor. Biochemistry 28: 1396–1405PubMedCrossRefGoogle Scholar
  21. Mishina M, Kurosaki T, Tobimatsu T, Morimoto Y, Noda M, Yamamoto T, Terao M, Lindstrom J, Takahashi T, Kuno M, Numa S (1984) Expression of functional acetylcholine receptor from cloned cDNAs. Nature 307: 604–608PubMedCrossRefGoogle Scholar
  22. Mishina M, Takai T, Imoto K, Noda M, Takahashi T, Numa S, Methfessel C, Sakmann B (1986) Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature 321: 406–411PubMedCrossRefGoogle Scholar
  23. Nathans J, Thomas D, Hogness DS (1986) Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science 232: 193–202PubMedCrossRefGoogle Scholar
  24. Noda M, Ikeda T, Suzuki H, Takeshima H, Takahashi T, Kuno M, Numa S, (1986) Expression of functional sodium channels from cloned cDNA. Nature 322: 826–828PubMedCrossRefGoogle Scholar
  25. Noda M, Shimizu S, Tanabe T, Takai T, Kayano T, Ikeda T, Takahashi H, Nakayama H, Kanaoka Y, Minamino N, Kangawa K, Matsuo H, Raftery MA, Hirose T, Inayama S, Hayashida H, Miyata T, Numa S (1984) Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312: 121–127PubMedCrossRefGoogle Scholar
  26. Noda M, Takahashi H, Tanabe T, Toyosato M, Furutani Y, Hirose T, Asai M, Inayama S, Miyata T, Numa S (1982) Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature 299: 793–797PubMedCrossRefGoogle Scholar
  27. Oberthiir W, Muhn P, Baumann H, Lottspeich F, Wittmann-Liebold B, Hucho F (1986) The reaction site of a non-competitive antagonist in the w-subunit of the nicotinic acetylcholine receptor. EMBO J 5:(8)1815–1819Google Scholar
  28. Ratnam M, Le Nguyen DL, Sargent PB, Lindstrom J (1986a) Transmembrane topology of nicotinic acetylcholine receptor: Immunochemical tests contradict theoretical predictions based on hydrophobicity profiles. Biochemistry 25: 2633–2643PubMedCrossRefGoogle Scholar
  29. Sanchez JA, Dani JA, Siemen D, Hille B (1986) Slow permeation of organic cations in acetylcholine receptor channels. J Gen Physiol 87: 985–1001PubMedCrossRefGoogle Scholar
  30. Schumacher M, Camp S, Manlet Y, Newton M, MacPhee-Quigley K, Taylor SS, Friedmann T, Taylor P (1986) Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence. Nature 319: 407–409PubMedCrossRefGoogle Scholar
  31. Smart L, Meyers H-W, Hilgenfeld R, Saenger W, Maelicke A (1984) A structural model for the ligand-binding sites at the nicotinic acetylcholine receptor. FEBS Letters 178: 64–68CrossRefGoogle Scholar
  32. Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S (1987) Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 328: 313–318PubMedCrossRefGoogle Scholar
  33. Young EF, Ralston E, Blake J, Ramachandran J, Hall ZW, Stroud RM (1985) Topological mapping of acetylcholine receptor: evidence for a model with five transmembrane segments and a cytoplasmic COOH-terminal peptide. Proc Natl Acad Sci USA 82: 626–630PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Alfred Maelicke
    • 1
  1. 1.Max-Planck-Institut für ErnährungsphysiologieDortmund 1Germany

Personalised recommendations