Molecular Properties of Voltage-Sensitive Sodium Channels

  • William A. Catterall
Part of the New Horizons in Therapeutics book series (NHTH)


Electrical excitability is one of the most important and characteristic properties of neurons. Most vertebrate cells, including neurons, maintain large ionic gradients across their surface membranes such that the intracellular fluid contains a high concentration of potassium ions and low concentrations of sodium ions and calcium ions relative to the extracellular fluid. These large ion gradients are maintained by the action of energy-dependent ion pumps specific for Na+ and K+, or for Ca2+. In addition, essentially all vertebrate cells maintain an internally negative membrane potential of the order of -60 mV, since their surface membranes are specifically permeable to K+, and this allows K+ to leak out of cells faster than Na+ and Ca2+ can leak in. Nerve cells are electrically excitable because of the presence, in their surface membranes, of voltage-sensitive ion channels that are selective for Na+, K+, or Ca2+. One class of Na+ channels and many classes of Ca2+ and K+ channels have been described in neurons. The channels open and close as a function of membrane voltage, allowing rapid movement of the appropriate ions down their concentration gradient so that ionic current passes into or out of the cell, depolarizing or hyperpolarizing the membrane.


Sodium Channel Scorpion Toxin Electrical Excitability Phosphatidylcholine Vesicle Sodium Channel Protein 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agnew, W. S., Moore, A. C., Levinson, S. R., and Raftery, M. A., 1980, Identification of a large molecular weight peptide associated with a tetrodotoxin binding protein from the electroplax of Electrophorus electricus, Biochem. Biophys. Res. Commun. 92:860–866.CrossRefGoogle Scholar
  2. Barchi, R. L., 1983, Protein components of the purified sodium channel from rat skeletal muscle sarcolemma, J. Neurochem. 40:1377–1385.PubMedCrossRefGoogle Scholar
  3. Barchi, R. L., and Murphy, L. E., 1981, Estimate of the molecular weight of the sarcolemmal sodium channel using H2O-D2O centrifugation, J. Neurochem. 36:2097–2100.PubMedCrossRefGoogle Scholar
  4. Barhanin, J., Schmid, A., Lombet, A., Wheeler, K. P., and Lazdunski, M., 1983, Molecular size of different neurotoxin receptors on the voltage-sensitive Na+ channel, J. Biol. Chem. 258:700–702.PubMedGoogle Scholar
  5. Beneski, D. A., and Catterall, W. A., 1980, Covalent labeling of protein components of the sodium channel with a photoactivable derivative of scorpion toxin, Proc. Natl. Acad. Sci. U.S.A. 77:639–643.PubMedCrossRefGoogle Scholar
  6. Benzer, T. I., and Raftery, M. A., 1973, Solubilization and partial characterization of the tetrodotoxin binding component from nerve axons, Biochem. Biophys. Res. Commun. 51:939–944.PubMedCrossRefGoogle Scholar
  7. Casadei, J. M., Gordon, R. D., Lampson, L. A., Schotland, D. L., and Barchi, R. L., 1984, Monoclonal antibodies against the voltage-sensitive Na+ channel from mammalian skeletal muscle, Proc. Natl. Acad. Sci. U.S.A. 81:6227–6231.PubMedCrossRefGoogle Scholar
  8. Catterall, W. A., 1980, Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes, Annu. Rev. Pharmacol. Toxicol. 20:15–43.PubMedCrossRefGoogle Scholar
  9. Catterall, W. A., 1984, The molecular basis of neuronal excitability. Science 223:653–661.PubMedCrossRefGoogle Scholar
  10. Catterall, W. A., Morrow, C. S., and Hartshorne, R. P., 1979, Neurotoxin binding to receptor sites associated with voltage-sensitive sodium channels in intact, lysed, and detergent-solubilized brain membranes, J. Biol. Chem. 254:11379–11387.PubMedGoogle Scholar
  11. Cohen, S. A., and Barchi, R. L., 1981, Glycoprotein characteristics of the sodium channel saxitoxin-binding component from mammalian sarcolemma, Biochem. Biophys. Acta 645:253–261.PubMedCrossRefGoogle Scholar
  12. Conti, F., Hille, B., Neumcke, B., Nonner, W., and Stampfli, R., 1976, Conductance of the sodium channel in myelinated nerve fibres with modified sodium inactivation, J. Physiol. (Lond.) 262:729–742.Google Scholar
  13. Costa, M. R. C., and Catterall, W. A., 1984, Cyclic AMP-dependent phosphorylation of the a subunit of the sodium channel in synaptic nerve ending particles, J. Biol. Chem. 259:8210–8218.PubMedGoogle Scholar
  14. Darbon, H., Jover, E., Couraud, P., and Rochat, H., 1983, Photoaffmity labeling of a- and β-scorpion toxin receptors associated with rat brain sodium channel, Biochem. Biophys. Res. Commun. 115:415–422.PubMedCrossRefGoogle Scholar
  15. Feller, D., Talvenheimo, J. A., and Catterall, W. A., 1985, The sodium channel from rat brain: Reconstitution of voltage-dependent scorpion toxin binding in vesicles of defined lipid composition, J. Biol. Chem. 260:11542–11547.PubMedGoogle Scholar
  16. Hartshorae, R. P., and Catterall, W. A., 1981, Purification of the saxitoxin receptor of the sodium channel from rat brain, Proc. Natl. Acad. Sci. U.S.A. 78:4620–4624.CrossRefGoogle Scholar
  17. Hartshome, R. P., and Catterall, W. A., 1984, The sodium channel from rat brain. Purification and subunit composition, J. Biol. Chem. 259:1667–1675.Google Scholar
  18. Hartshome, R. P., Coppersmith, J., and Catterall, W. A., 1980, Size characteristics of the solubihzed saxitoxin receptor of the voltage sensitive sodium channel from rat brain, J. Biol. Chem. 255:10572–10515.Google Scholar
  19. Hartshome, R. P., Messner, D. J., Coppersmith, J. C., and Catterall, W. A., 1982, The saxitoxin receptor of the sodium channel from rat brain. Evidence for two nonidentical ß subunits, J. Biol. Chem. 257:13888–13891.Google Scholar
  20. Hartshome, R. P., Keller, B. U., Talvenheimo, J. A., Catterall, W. A. and Montal, M., 1985, Functional reconstitution of the purified brain sodium channel in planar lipid bilayers, Proc. Natl. Acad. Sci. U.S.A. 82:240–244.CrossRefGoogle Scholar
  21. Henderson, R., and Wang, J. H., 1972, Solubilization of a specific tetrodotoxin-binding component from garfish olfactory nerve membrane. Biochemistry 11:4565–4569.PubMedCrossRefGoogle Scholar
  22. Hille, B., 1972, The permeability of the sodium channel to metal cations in myelinated nerve, J. Gen. Physiol. 59:637–658.PubMedCrossRefGoogle Scholar
  23. Hodgkin, A. L., and Huxley, A. F., 1952, A quantitive description of membrane current and its application to conduction and excitation in nerve, J. Physiol. (Lond.) 117:500–544.Google Scholar
  24. Jover, E., Covraud, F., and Rochat, H., 1980, Two types of scorpion neurotoxins characterized by their binding to two separate receptor sites on rat brain synaptosomes, Bioehem. Biophys. Res. Comm. 95:1607–1614.CrossRefGoogle Scholar
  25. Levinson, S. R., and Ellory, J. C., 1973, Molecular size of the tetrodotoxin binding site estimated by irradiation inactivation, Nature (New Biol.) 245:122–123.CrossRefGoogle Scholar
  26. Lombet, A., and Lazdunski, M., 1984, Characterization, solubilization, affinity labeling and purification of the cardiac Na+ channel using Tityus toxin, Eur. J. Bioehem. 141:651–660.CrossRefGoogle Scholar
  27. Lombet, A., Norman, R. I., and Lazdunski, M., 1983, Affinity labeling of the tetrodotoxin-binding component of the Na+ channel, Bioehem. Biophys. Res. Commun. 114:126–130.CrossRefGoogle Scholar
  28. Messner, D. J., and Catterall, W. A., 1985, The sodium channel from rat brain. Separation and characterization of subunits, J. Biol. Chem. 260:10597–10604.PubMedGoogle Scholar
  29. Nöda, M., Shimizu, S., Tanabe, T., Takai, T., Kayano, T., Ikeda, T., Takahashi, H., Nakayama, H., Kanaoka, Y., Minamino, N., Kangawa, K., Mutsuo, H., Raftery, M. A., Hirose, T., Inayama, S., Hayashida, H., Miyata, T., and Numa, S., 1984, Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence, Nature 312:121–127.PubMedCrossRefGoogle Scholar
  30. Ritchie, J. M., and Rogart, R. B., 1977, The binding of saxitoxin and tetrodotoxin to excitable tissue. Rev. Physiol. Bioehem. Pharmacol. 79:1–51.CrossRefGoogle Scholar
  31. Sigworth, P. J., and Neher, E., 1980, Single Na+ channel currents observed in cuhured rat muscle cells, Nature 287:447–449.PubMedCrossRefGoogle Scholar
  32. Talvenheimo, J. A., Tamkun, M. M., and Catterall, W. A., 1982, Reconstitution of neurotoxin-stimulated sodium transport by the voltage-sensitive sodium channel purified from rat brain, J. Biol. Chem. 257:11868–11871.PubMedGoogle Scholar
  33. Tamkun, M. M., Talvenheimo, J. A., and Catterall, W. A., 1984, The sodium channel from rat brain. Reconstitution of neurotoxin-activated ion flux and scorpion toxins binding from purified components, J. Biol. Chem. 259:1676–1688.PubMedGoogle Scholar
  34. Weigele, J. B., and Barchi, R. L., 1982, Functional reconstitution of the purified sodium channel protein from rat sarcolemma, Proc. Natl. Acad. Sci. U.S.A. 79:3651–3655.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • William A. Catterall
    • 1
  1. 1.Department of PharmacologyUniversity of WashingtonSeattleUSA

Personalised recommendations