Metabolic Regulation of Ion Channels

  • Irwin B. Levitan
Part of the Series of the Centro de Estudios Científicos de Santiago book series (SCEC)


During the last 30 years a great deal of progress has been made in our understanding of how neurotransmitters can regulate the activity of excitable cells. Much of our knowledge has come from studies on the vertebrate neuromuscular junction, in part because the preparation is easily accessible for experimental manipulation, but perhaps more importantly because a series of brilliant investigators have made it the focus of their highly imaginative studies. The resulting body of work has given us a detailed molecular picture of the nicotinic acetylcholine receptor/channel as a single macromolecular complex that can both bind acetylcholine and mediate the transport of ions across the plasma membrane. The opening of the channel (and transport of ions) is rapid in onset after the binding of acetylcholine to the receptor and is rapidly reversible when the receptor is no longer occupied by the agonist. Figure 1A summarizes schematically this way of thinking of rapidly reversible changes in the activity of an ion channel as being dependent on the continued occupation of a closely associated receptor by an agonist.


Behavioral Sensitization Protein Kinase Inhibitor Dependent Protein Kinase Excitable Cell Rectify Potassium Channel 
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  1. Adams, W. B., and Levitan, I. B., 1982, Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance in Aplysia neuron R15, Proc. Natl. Acad. Sci. U.S.A. 79:3877–3880.PubMedCrossRefGoogle Scholar
  2. Alkon, D. L., Acosta-Urquidi, J., Olds, J., Kuzma, G., and Neary, J. T., 1983, Protein kinase injection reduces voltage-dependent potassium currents, Science 219:303–306.PubMedCrossRefGoogle Scholar
  3. Brunelli, M., Castellucci, V., and Kandel, E., 1976, Synaptic facilitation and behavioral sensitization in Aplysia: Possible role of serotonin and cyclic AMP, Science 194:1178–1181.PubMedCrossRefGoogle Scholar
  4. Camardo, J., Shuster, M., Siegelbaum, S., Eppler, C., and Kandel, E., 1983, Purified catalytic subunit of cyclic AMP-dependent protein kinase closes the serotonin-sensitive potassium channel of Aplysia sensory neurons in cell-free membrane patches, Soc. Neurosci. Abstr. 9:22.Google Scholar
  5. Castellucci, V. F., Kandel, E. R., Schwartz, J. H., Wilson, F. D., Nairn, A. C., and Greengard, P., 1980, Intracellular injection of the catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia, Proc. Natl. Acad. Sci. U.S.A. 77:7492–7496.CrossRefGoogle Scholar
  6. Castellucci, V. F., Nairn, A., Greengard, P., Schwartz, J. H., and Kandel, E. R., 1982, Inhibitor of adenosine 3’:5’-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia, J. Neurosci. 2:1673–1681.Google Scholar
  7. Cohen, P., 1982, The role of protein phosphorylation in neural and hormonal control of cellular activity, Nature 296:613–620.PubMedCrossRefGoogle Scholar
  8. Coronado, R., and Latorre, R., 1983, Phospholipid bilayers made from monolayers on patch-clamp pipettes, Biophys. J. 43:231–236.PubMedCrossRefGoogle Scholar
  9. Demaille, J., Peters, K., and Fischer, E., 1977, Isolation and properties of the rabbit skeletal muscle protein inhibitor of adenosine 3′,5′-monophosphate dependent protein kinases, Biochemistry 16:3080–3086.PubMedCrossRefGoogle Scholar
  10. DePeyer, J. E., Cachelin, A. B., Levitan, I. B., and Reuter, H., 1982, Ca2+-Activated K + conductance in internally perfused snail neurons is enhanced by protein phosphorylation, Proc. Natl. Acad. Sci. U.S.A. 79:4207–4211.CrossRefGoogle Scholar
  11. Deterre, P., Paupardin-Tritsch, D., Bockaert, J., and Gerschenfeld, H. M., 1981, Role of cyclic AMP in a serotonin-evoked slow inward current in snail neurones, Nature 290:783–785.PubMedCrossRefGoogle Scholar
  12. Drummond, A., Benson, J., and Levitan, I. B., 1980, Serotonin-induced hyperpolarization of an identified Aplysia neuron is mediated by cyclic AMP, Proc. Natl. Acad. Sci. U.S.A. 77:5013–5017.PubMedCrossRefGoogle Scholar
  13. Ewald, D. A., Williams, A., Levitan, I.B., 1985, Modulation of single calcium-dependent potassium channel activity by protein phosphorylation, Nature 315:503–506.PubMedCrossRefGoogle Scholar
  14. Glass, D., and Krebs, E., 1980, Protein phosphorylation catalyzed by cyclic AMP-dependent and cyclic GMP-dependent protein kinases, Annu. Rev. Pharmacol. Toxicol. 20:363–388.PubMedCrossRefGoogle Scholar
  15. Hamill, O. P., Marty, A., Neher, E., Sakmann, B., and Sigworth, F. J., 1981, Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches, Pfluegers Arch. 391:85–100.CrossRefGoogle Scholar
  16. Kaczmarek, L., Jennings, K., and Strumwasser, F., 1978, Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neuntes, Proc. Natl. Acad. Sci. U.S.A. 75:5200–5204.PubMedCrossRefGoogle Scholar
  17. Kaczmarek, L. K., Jennings, K. R., Strumwasser, F., Nairn, A. C., Walter, U., Wilson, F. D., and Greengard, P., 1980, Microinjection of catalytic subunit of cyclic AMP-dependent protein kinase enhances calcium action potentials of bag cell neurons in cell culture, Proc. Natl. Acad. Sci. U.S.A. 77:7487–7491.PubMedCrossRefGoogle Scholar
  18. Klein, M., and Kandel, E., 1978, Presynaptic modulation of voltage-dependent Ca2+ current: Mechanism for behavioral sensitization in Aplysia californica, Proc. Natl. Acad. Sci. U.S.A. 75:3512–3516.CrossRefGoogle Scholar
  19. Kuo, J., and Greengard, P., 1969, Cyclic nucleotide-dependent protein-kinases, IV. Widespread occurrence of adenosine 3′,5′-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom, Proc. Natl. Acad. Sci. U.S.A. 64:1349–1355.PubMedCrossRefGoogle Scholar
  20. Levitan, I. B., and Norman, J., 1980, Different effects of cAMP and cGMP derivatives on the activity of an identified neuron: Biochemical and electrophysiological analysis, Brain Res. 187:415–429.PubMedCrossRefGoogle Scholar
  21. Maruyama, Y., and Petersen, O. H., 1982, Cholecystokinin activation of single-channel currents is mediated by internal messenger in pancreatic acinar cells, Nature 300:61–63.PubMedCrossRefGoogle Scholar
  22. Miller, C., 1983, Integral membrane channels: Studies in model membranes, Physiol. Rev. 63:1209–1242.PubMedGoogle Scholar
  23. Neher, E., and Sakmann, B., 1976, Single-channel currents recorded from membrane of denervated frog muscle fibers, Nature 260:799–802.PubMedCrossRefGoogle Scholar
  24. Osterrieder, W., Brum, G., Hescheler, J., Trautwein, W., Flockerzi, V., and Hofmann, F., 1982, Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current, Nature 298:576–578.PubMedCrossRefGoogle Scholar
  25. Pellmar, T. C., 1981, Ionic mechanism of a voltage-dependent current elicited by cyclic AMP, Cell Mol. Neurobiol. 1:87–97.PubMedCrossRefGoogle Scholar
  26. Peters, K., Demaille, J., and Fischer, E., 1977, Adenosine 3’:5’-monophosphate dependent protein kinase from bovine heart. Characterization of the catalytic subunit, Biochemistry 16:5691–5697.PubMedCrossRefGoogle Scholar
  27. Shuster, M., Camardo, J., Siegelbaum, S., Kandel, E. R., 1985, Cyclic AMP-dependent protein kinase closes the serotonin-sensitive potassium channels of Aplysia sensory neurons in cell-free membrane patches, Nature 313:392–395.PubMedCrossRefGoogle Scholar
  28. Siegelbaum, S. A., Camardo, J. S., and Kandel, E. R., 1982, Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones, Nature 299:413–417.PubMedCrossRefGoogle Scholar
  29. Treistman, S. N., 1981, Effect of adenosine 3′,5′-monophosphate on neuronal pacemaker activity: A voltage clamp analysis, Science 211:59–61.PubMedCrossRefGoogle Scholar
  30. Treistman, S. N., and Levitan, I. B., 1976a, Alteration of electrical activity in molluscan neurones by cyclic nucleotides and peptide factors, Nature 261:62–64.CrossRefGoogle Scholar
  31. Treistman, S. N., and Levitan, I. B., 1976b, Intraneuronal guanylyl-imidodiphosphate injection mimics long-term synaptic hyperpolarization in Aplysia, Proc. Natl. Acad. Sci. U.S.A. 73:4689–4692.CrossRefGoogle Scholar
  32. Tsien, R. W., 1973, Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac purkinje fibers, Nature (New Biol.) 245:120–122.CrossRefGoogle Scholar
  33. Tsien, R. W., 1977, Cyclic AMP and contractile activity in heart, Adv. Cyclic Nucleotide Res. 8:363–420.PubMedGoogle Scholar
  34. Walsh, D., and Ashby, C., 1973, Protein kinases: Aspects of their regulation and diversity, Recent Prog. Horm. Res. 29:329–359.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Irwin B. Levitan
    • 1
  1. 1.Graduate Department of BiochemistryBrandeis UniversityWalthamUSA

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