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The Structure of the Ca2+ Channel: Photoaffinity Labeling and Tissue Distribution

  • Conference paper
The Calcium Channel: Structure, Function and Implications

Part of the book series: Bayer AG Centenary Symposium ((BAYER))

Abstract

Photoaffinity labeling is an important, extremely valuable tool for the characterization of pharmacological receptors. Radioactive photoaffinity probes allow, even in crude preparations with very low receptor densities, identification of the polypeptide(s) which bind the ligand. In general, the photoaffinity protection profile (obtained by adding unlabeled compounds interacting competitively or allosterically with the receptor) should reflect the reversible binding interaction profile. In Ca2+ channel research, three arylazide photo affinity probes are useful, namely ( - )- or (±)[3H]azidopine (1,4-dihydropyridines), [N-methyl-3H]LU49888 (a phenylalkylamine), and an azido derivative of [125I]ω-conotoxin GVIA (CgTx). The first two ligands are well characterized by reversible binding experiments and interact in a stereoselective manner and with high affinity with L-type Ca2+ channels [1-5]. The 125I-iodinated CgTx photoaffinity probe presumably incorporates into the N-type channel components, exclusively found in neuronal tissues [6]. L-type Ca2+ channels have distinct drug-receptor domains for different classes of drugs (e.g., the 1,4-dihydropyridines, phenylalkylamines, and benzothiazepines) linked to each other (and to high- and low-affinity divalent cation binding sites) by reciprocal allosteric coupling mechanisms [7]. Recently, the benzothiazinones [8] and diphenylbutylpiperidines [9, 10] have been suggested to act at yet another site.

Research of H. G. was supported by the Deutsche Forschungsgemeinschaft, Dr. Legerlotz Foundation, and Jubiläumsfonds der Nationalbank. H.G. and H.S. are funded by a Schwerpunktprogramm of the Austrian Fonds zur Förderung der Wissenschaftlichen Forschung.

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Author information

Authors and Affiliations

  1. Institut für Biochemische Pharmakologie, Universität Innsbruck, A-6020, Innsbruck, Austria

    H. Glossmann, J. Striessnig, G. Zernig & H. G. Knaus

  2. Institut für Biophysik, Universität Linz, A-4020, Linz, Austria

    L. Hymel & H. Schindler

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  1. H. Glossmann
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  2. J. Striessnig
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  3. L. Hymel
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  4. G. Zernig
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  5. H. G. Knaus
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  6. H. Schindler
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Editor information

Editors and Affiliations

  1. Department of Physiology, University of Pennsylvania, Philadelphia, PA, 19104-6085, USA

    Martin Morad (Professor of Physiology and Medicine) (Professor of Physiology and Medicine)

  2. Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, 3084, Victoria, Australia

    Winifred G. Nayler (Principal Research Investigator) (Principal Research Investigator)

  3. Bayer AG, Institute of Pharmacology, Aprather Weg 18a, D-5600, Wuppertal 1, Germany

    Stanislav Kazda (Associate Professor of Pharmacology and Toxicology) & Matthias Schramm (Associate Professor of Physiology) (Associate Professor of Pharmacology and Toxicology) &  (Associate Professor of Physiology)

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Glossmann, H., Striessnig, J., Hymel, L., Zernig, G., Knaus, H.G., Schindler, H. (1988). The Structure of the Ca2+ Channel: Photoaffinity Labeling and Tissue Distribution. In: Morad, M., Nayler, W.G., Kazda, S., Schramm, M. (eds) The Calcium Channel: Structure, Function and Implications. Bayer AG Centenary Symposium. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73914-9_15

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  • DOI: https://doi.org/10.1007/978-3-642-73914-9_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-50061-2

  • Online ISBN: 978-3-642-73914-9

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