Phosphorylation of Ion Channels: A Fundamental Regulatory Mechanism in the Control of Nerve Cell Activity

  • I. B. Levitan
Conference paper
Part of the Colloquium der Gesellschaft für Biologische Chemie 18.–20. April 1985 in Mosbach/Baden book series (MOSBACH, volume 36)

Abstract

There has been much progress in recent years in our understanding of the molecular mechanisms by which neurotransmitters exert their effects on excitable cells. On the one hand, studies of the structure and function of the nicotinic acetylcholine receptor have provided a detailed picture of a directly coupled receptor/channel system, a system in which the opening of an ion channel (and transport of ions) is dependent on the continued occupation of a closely associated receptor by the transmitter. However, there are many examples of physiological responses which outlast the initial stimulus, the occupancy of the receptor by the transmitter, by seconds, minutes, or even hours. It is difficult to explain such long-lasting effects in terms of direct receptor/channel coupling, and it seems more likely that it results from some long-lasting metabolic modification of the channel. In this case the receptor and channel may not necessarily be intimately associated in a single macromolecular complex, but may be indirectly coupled via some intracellular second messenger which is produced upon occupancy of receptor by neurotransmitter.

Keywords

Hydrolysis Carbohydrate Adenosine Serotonin Polyacrylamide 

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References

  1. Adams WB, Levitan IB (1982) Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance in Aplysia neuron R15. Proc Natl Acad Sci USA 79:3877–3880PubMedCrossRefGoogle Scholar
  2. Alkon DL, Acosta-Urquidi J, Olds J, Kuzma G, Neary JT (1983) Protein kinase injection reduces voltage-dependent potassium currents. Science 219:303–306PubMedCrossRefGoogle Scholar
  3. Benson JA, Levitan IB (1983) Serotonin increases an anomalously rectifying K+ current in the Aplysia neuron R15. Proc Natl Acad Sci USA 80:3522–3525PubMedCrossRefGoogle Scholar
  4. Castellucci VF, Kandel ER, Schwartz JH, Wilson FD, Nairn AC, 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 USA 77:7492–7496PubMedCrossRefGoogle Scholar
  5. Castellucci VF, Nairn A, Greengard P, Schwartz JH, Kandel ER (1982) Inhibitor of Adenosine 3′:5′-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia. J Neurosci 2:1673–1681PubMedGoogle Scholar
  6. Cohen P (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature (London) 296:613–620CrossRefGoogle Scholar
  7. Demaille J, Peters K, Fischer E (1977) Isolation and properties of the rabbit skeletal muscle protein inhibitor of cAMP-dependent protein kinases. Biochemistry 16:3080–3086PubMedCrossRefGoogle Scholar
  8. De Peyer JE, Cachelin AB, Levitan IB, Reuter H (1982) Ca2+-activated K+ conductance in internally perfused snail neurons is enhanced by protein phosphorylation. Proc Natl Acad Sci USA 79:4207–4211PubMedCrossRefGoogle Scholar
  9. De Riemer SA, Strong JA, Albert KA, Greengard P, Kaczmarek LK (1985) Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C. Nature (London) 313:313–316CrossRefGoogle Scholar
  10. Drummond AH, Benson JA, Levitan IB (1980) Serotonin-induced hyperpolarization of an identified Aplysia neuron is mediated by cyclic AMP. Proc Natl Acad Sci USA 77:5013–5017PubMedCrossRefGoogle Scholar
  11. Ewald D, Williams A, Levitan IB (1985) Modulation of single Ca++-dependent K+ channel activity by protein phosphorylation. Nature 315:503–506PubMedCrossRefGoogle Scholar
  12. Glass DB, Krebs EG (1980) Protein phosphorylation catalyzed by cyclic AMP-dependent and cyclic GMP-dependent protein kinases. Annu Rev Pharmacol Toxicol 20:363–388PubMedCrossRefGoogle Scholar
  13. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pfluegers Arch 391:81–100CrossRefGoogle Scholar
  14. Kaczmarek LK, Jennings KR, Strumwasser F, Nairn AC, Walter U, Wilson FD, 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 USA 77:7487–7491PubMedCrossRefGoogle Scholar
  15. Kuo JF, 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 USA 64:1359–1365CrossRefGoogle Scholar
  16. Lemos JR, Novak-Hofer I, Levitan IB (1982) Serotonin alters the phosphorylation of specific proteins inside a single living nerve cell. Nature (London) 298:64–65CrossRefGoogle Scholar
  17. Lemos JR, Novak-Hofer I, Levitan IB (1984) Synaptic stimulation alters protein phosphorylation in vivo in a single Aplysia neuron. Proc Natl Acad Sci USA 81:3233–3237PubMedCrossRefGoogle Scholar
  18. Lemos JR, Novak-Hofer I, Levitan IB (1985) Phosphoproteins associated with the regulation of a specific potassium channel in the identified Aplysia neuron R15. J Biol Chem 260:3207–3214PubMedGoogle Scholar
  19. Levitan IB (1978) Adenylate cyclase in isolated Helix and Aplysïa neuronal cell bodies: stimulation by serotonin and peptide-containing extract. Brain Res 154:404–408PubMedCrossRefGoogle Scholar
  20. Levitan IB, Lemos JR, Novak-Hofer I (1983) Protein phosphorylation and the regulation of ion channels. Trends Neurosciences 6:496–499CrossRefGoogle Scholar
  21. Maruyama Y, Petersen OH (1982) Cholecystokinin activation of single-channel currents is mediated by internal messenger in pancreatic acinar cells. Nature (London) 300:61–63CrossRefGoogle Scholar
  22. Miller C (1983) Integral membrane channels: studies in model membranes. Physiol Rev 63:1209–1242PubMedGoogle Scholar
  23. Osterrieder W, Brum G, Hescheler J, Trautwein W, Flockerzi V, Hofmann F (1982) Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature (London) 298:576–578CrossRefGoogle Scholar
  24. Peters KA, Demaille JG, Fischer EH (1977) Adenosine 3′:5′-monophosphate-dependent protein kinase from bovine heart. Characterization of the catalytic subunit. Biochemistry 16:5691–5697PubMedCrossRefGoogle Scholar
  25. Shuster M, Camardo J, Siegelbaum S, Kandel ER (1985) Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches. Nature (London) 313:392–395CrossRefGoogle Scholar
  26. Siegelbaum SA, Tsien RW (1983) Modulation of gated ion channels as a mode of transmitter action. Trends Neurosci 6:307–313CrossRefGoogle Scholar
  27. Siegelbaum SA, Camardo JS, Kandel ER (1982) Serotonin and cyclic AMP close single K+ channels in Aplysïa sensory neurones. Nature (London) 299:413–417CrossRefGoogle Scholar
  28. Wilmsen U, Methfessel C, Hanke W, Boheim G (1983) Channel current fluctuation studies with solvent-free lipid bilayers using Neher-Sakmann pipettes. In: Physical chemistry of transmembrane ion motions. Elsevier, Amsterdam, pp 479–485Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

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

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