Skip to main content
SpringerLink
Log in

Molecular Mechanisms of Neuronal Excitability: Possible Involvement of CaM Kinase II in Seizure Activity

  • Chapter
Book cover Molecular Mechanisms of Neuronal Responsiveness

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 221))

Abstract

An understanding of the molecular mechanisms that underlie neuronal responsiveness is an important goal of contemporary neuroscience. The specific biochemical events that modulate excitability of neurons and neuronal systems will provide important insights into the complex regulatory mechanisms of the nervous system. In the clinical neurosciences, an understanding of these molecular events may provide significant avenues for the development of treatment protocols for diseases of the nervous system.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Acosta-Urquidi, J., Neary, J. T., Goldenring, J. R., Alkon, D. L. and DeLorenzo, R. J., Modulation of ICa and late K+ currents by intrasomatic injection of Ca-calmodulin dependent kinase in Hermissenda giant neurons, Soc. Neurosci. Abstrs., 10: 1129 (1984a).

    Google Scholar 

  • Acosta-Urquidi, J., Alkon, D. L. and Neary, J. T., Ca2+-dependent protein kinase injection in a photoreceptor mimics biophysical effects of associative learning, Science 224: 1254–1257 (1984b).

    Article  CAS  Google Scholar 

  • Alkon, D. L., Neural correlates of associative training in Hermissenda, J. Gen. Physiol., 65: 46–56 (1975).

    Article  CAS  Google Scholar 

  • Alkon, D. L., Voltage-dependent calcium and potassium conductances: a contingency mechanism for an associative learning model, Science 205: 810–816 (1979).

    Article  CAS  Google Scholar 

  • Alkon, D. L., Shoukimas, J. J. and Heldman, E., Calcium mediated decrease of a voltage-dependent potassium current, Biophys. J., 40: 245–250 (1982a).

    Article  CAS  Google Scholar 

  • Alkon, D. L., Lederhendler, I. and Shoukimas, J. J., Primary changes of membrane currents during retention of associative learning, Science 215: 693–695 (1982b).

    Article  CAS  Google Scholar 

  • Alkon, D. L., Acosta-Urquidi, J., Olds, J., Kuzma, G. and Neary, J., Protein kinase injection reduces voltage-dependent potassium currents, Science 219: 303–306, (1983).

    Article  CAS  Google Scholar 

  • Alkon, D. L., Calcium-mediated reduction of ionic currents: a biophysical memory trace, Science 226: 1037–1045, (1984).

    Article  CAS  Google Scholar 

  • Alkon, D. L., Farley, J., Sakakibara, M. and Hay, B., Voltage-dependent calcium and calcium-activated potassium currents of a molluscan photoreceptor, Biophys. J. 46: 605–614 (1984).

    Article  CAS  Google Scholar 

  • Alkon, D. L. and Sakakibara, M., Prolonged inactivation of a Ca2+ dependent K+ current but not Ca2+ current by light induced elevation of intracellular calcium, Soc. Neurosci. Abstr. 10: 10 (1984).

    Google Scholar 

  • Alkon, D. L., Sakakibara, M., Forman, R. R., Harrigan, J., Lederhendler, I. and Farley, J., Reduction of two voltage-dependent K+ currents mediates retention of a learned association, Behav. Neural Biol. 44: 278–300 (1985).

    Article  CAS  Google Scholar 

  • Alkon, D. L. and Sakakibara, M., Calcium activates and inactivates a photoreceptor soma K current, Biophys. J., in press (1986).

    Google Scholar 

  • Aloyo, V. J., Zweirs, H. and Gispen, W. H., B-50 protein kinase and kinase C in rat brain, Prog. Brain Res. 56: 303–315 (1982).

    Article  CAS  Google Scholar 

  • Baraban, J. M., Snyder, S. H. and Alger, B. E., Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons: electrophysiological effects of phorbol esters, Proc. Natl. Acad. Sci. USA 82: 2538–2542 (1985).

    Article  CAS  Google Scholar 

  • Bennett, M. K., Erondu, N. E. and Kennedy, M. B., Purification and characterization of a calmodulin-dependent protein kinase that is highly concentrated in brain, J. Biol. Chem. 258: 12735–12744 (1983).

    CAS  Google Scholar 

  • Burke, B. and DeLorenzo, R. J., Calcium and calmodulin regulated endogenous tubulin kinase activity in synaptic nerve terminal preparations, Brain Res., 236: 393–415 (1982).

    Article  CAS  Google Scholar 

  • Byrne, M. C., Gottlieb, R., and McNamara, J. O., Amygdala kindling induces muscarinic cholinergic receptor declines in a highly specific distribution within the limbic system, Exp. Neurol. 69: 85–98 (1980).

    Article  CAS  Google Scholar 

  • Castelluci, V. F., Kandel, E. R., Schwartz, J. H., Wilson, F. D., Nairn, A. C. and Greengard, P., 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: 7492–7496 (1980).

    Article  Google Scholar 

  • Cheung, W. Y., Calmodulin role in cellular regulation, Science 207: 19–27 (1980).

    Article  CAS  Google Scholar 

  • DeCamilli, P., Camerson, R. and Greengard, P., Synapsin I (Protein I), a nerve terminal specific phosphoprotein I: Its general distribution in synapses of the central and peripheral nervous system demonstrated by immuno-fluorescence in frozen and plastic sections, J. Cell Biol. 96: 1337–1354 (1983).

    Article  CAS  Google Scholar 

  • DeLorenzo, R. J., Calcium-dependent phosphorylation of specific synaptosomal fraction proteins: possible role of phosphoproteins in mediating neurotransmitter release, Biochem. Biophys. Res. Commun. 71: 590–597 (1976).

    Article  CAS  Google Scholar 

  • DeLorenzo, R. J., Freedman, S. D., Yohe, W. B. and Maurer, S. C., Stimulation of calcium-dependent neurotransmitter release and presynaptic nerve terminal protein phosphorylation by calmodulin and a calmodulinlike protein isolated from synaptic vesicles, Proc. Natl. Acad. Sci. USA 76: 1838–1842 (1979).

    Article  CAS  Google Scholar 

  • DeLorenzo, R. J., Role of calmodulin in neurotransmitter release and synaptic function, Ann. N. Y. Acad. Sci. 356: 92–109 (1980a).

    Article  CAS  Google Scholar 

  • DeLorenzo, R. J., Phenytoin: calcium-calmodulin-dependent protein phosphorylation and neurotransmitter release, in: “Antiepileptic Drugs: Mechanism of Action,” G. H. Glaser, J. K. Penry, and D. W. Woodbury, eds., Raven, New York, pp 399–414 (1980b).

    Google Scholar 

  • DeLorenzo, R. J., Calcium, calmodulin and synaptic function: modulation of neurotransmitter release, nerve terminal protein phosphorylations, and synaptic vesicle morphology by calcium and calmodulin, in: “Regulatory Mechanism of Synaptic Transmission,” R. Tapie and C. W. Cotman, eds., Plenum, New York and London, pp 205–240 (1981a).

    Chapter  Google Scholar 

  • DeLorenzo, R. J., The calmodulin hypothesis of neurotransmission, Cell Calcium 2: 365–385 (1981b).

    Article  CAS  Google Scholar 

  • DeLorenzo, R. J., Burdette, S. and Holderness, J., Benzodiazepine inhibition of the calcium-calmodulin protein kinase system in brain membrane, Science 213: 546–549 (1981).

    Article  CAS  Google Scholar 

  • DeLorenzo, R. J., Gonzales, B., Goldenring, J. R., Bowling, A. C. and Jacobson, R., Ca2+-calmodulin tubulin kinase system and its role in mediating the Ca2+ signal in brain, in: “Progress in Brain Research,” Volume 56, W. H. Gispen and A. Routtenberg, eds., Elsevier Biomedical Press, Amsterdam, pp. 255–286 (1982).

    Google Scholar 

  • DeLorenzo, R. J., Calmodulin in neurotransmitter release and synaptic function, Fed. Proc. 41: 2265–2272 (1982).

    CAS  Google Scholar 

  • DePeyer, J. E., Cachelin, A. B., Levitan, I. B. and Reuter, H., Ca2+-activated K+ conductance in internally perfused snail neurons is enhanced by protein phosphorylation, Proc. Natl. Acad. Sci. USA 79: 4207–4211 (1982).

    Article  CAS  Google Scholar 

  • DeRiemer, S., Strong, J., Albert, K., Greengard, P. and Kaczmarek, L., Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C., Nature 313: 313–316 (1985).

    Article  CAS  Google Scholar 

  • Douglas, W. W., Stimulus-secretion coupling: the concept and clues from chromaffin and other cells, Br. J. Pharmacol. 34: 451–474 (1968).

    Article  CAS  Google Scholar 

  • Farber, D. B. and Wasterlain, C. G., Inhibition of kindled seizure by diazepam: mediation by phosphoproteins?, Proc. Natl. Acad. Sci. USA, in press (1986).

    Google Scholar 

  • Farley, J. and Alkon, D. L., Membrane depolarization accumulates during acquisition of an associative behavioral change, Science 210: 1375–1376 (1980).

    Article  Google Scholar 

  • Farley, J. and Alkon, D. L., Associative neural and behavioral change in Hermissenda: consequences of nervous system orientation for light and pairing specificity, J. Neurophysiol. 48: 785–807 (1982).

    CAS  Google Scholar 

  • Farley, J. and Auerbach, S., Protein kinase C activation induces conductance changes in Hermissenda photoreceptors like those seen in associative learning, Nature 319: 220–223 (1986).

    Article  CAS  Google Scholar 

  • Fukunaga, K., Yamamoto, H., Matsui, K., Higashu, K. and Miyamoto, E., Purification and characterization of a Ca2+-calmodulin-dependent protein kinase from rat brain, J. Neurochem. 39: 1607–1617 (1982).

    Article  CAS  Google Scholar 

  • Gastaut, H., Jasper, H., Bancaud, J. and Waltregny, A., eds., “The Physiopathogenesis of the Epilepsies,” Charles C. Thomas, Springfield, Illinois (1969).

    Google Scholar 

  • Glaser, G. H., Epilepsy, in: “Recent Advances in Clinical Neurology,” W. P. Matthews, ed., Churchill-Livingston, London (1975).

    Google Scholar 

  • Glaser, G. H., Penry, J. K. and Woodbury, D. M., eds., “Antiepileptic Drugs: Mechanisms of Action,” Raven Press, New York (1980).

    Google Scholar 

  • Goddard, G. V., Mclntyre, D. C. and Leech, C. K., A permanent change in brain function resulting from daily electrical stimulation, Exp. Neurol. 25: 243–330 (1969).

    Article  Google Scholar 

  • Goldenring, J. R., Gonzalez, B. and DeLorenzo, R. J., Isolation of brain Ca2+-calmodulin tubulin kinase containing calmodulin binding proteins, Biochem. Biophys. Res. Commun. 108: 421–428 (1982).

    Article  CAS  Google Scholar 

  • Goldenring, J. R., Gonzalez, B., McGuire, J. S., Jr. and DeLorenzo, R. J., Purification and characterization of a calmodulin-dependent protein kinase from rat brain cytosol able to phosphorylate tubulin and microtubule-associated proteins, J. Biol. Chem. 258: 12632–12640 (1983).

    CAS  Google Scholar 

  • Goldenring, J. R., McGuire, J. S., Jr., and DeLorenzo, R. J., Identification of the major post-synaptic density protein as a homologous with the major calmodulin-binding subunit of a calmodulin-dependent protein kinase, J. Neurochem. 42: 1077–1084 (1984).

    Article  CAS  Google Scholar 

  • Goldenring, J. R., Vallano, M. L. and DeLorenzo, R. J., Phosphorylation of microtubule-associated protein 2 at distinct sites by calmodulin-dependent and cyclic-AMP-dependent kinases, J. Neurochem. 45: 900–905 (1985).

    Article  CAS  Google Scholar 

  • Goldenring, J. R., Wasterlain, C. G., Destreicher, A. B., deGraan, P. N. E., Farber, D. B., Glaser, G. and DeLorenzo, R. J., Kindling induces a long lasting change in the activity of a hippocampal membrane calmodulindependent protein kinase, Brain Res., in press (1986a).

    Google Scholar 

  • Grab, D. J., Berzins, K., Cohen, R. S. and Siekevitz, P., Presence of calmodulin in postsynaptic densities isolated from canine cerebral cortex, J. Biol. Chem. 254: 8690–8696 (1979).

    CAS  Google Scholar 

  • Grab, D. J., Carlin, R. K. and Siekevitz, P., The presence and functions of calmodulin in the postsynaptic density, Ann. N. Y. Acad. Sci. 356: 55–72 (1980).

    Article  CAS  Google Scholar 

  • Grab, D. J., Carlin, R. K. and Siekevitz, P., Function of calmodulin in postsynaptic density II. Presence of calmodulin-activable protein kinase activity, J. Cell Biol. 89: 440–448 (1981).

    Article  CAS  Google Scholar 

  • Hawkins, R. D., Abrams, T. W., Carew, T. J. and Kandel, E. R., Differential classical conditioning of a defensive withdrawal reflex in Aplysia californica, Science 219: 397–404 (1983).

    Article  Google Scholar 

  • Jasper, H. H., Ward, A. A., Jr. and Pope, A., eds., “Basic Mechanisms of the Epilepsies,” Little, Brown, Boston (1969).

    Google Scholar 

  • Kandel, E. R. and Schwartz, J. H., Molecular biology of learning: modulation of transmitter release, Science 218: 433–443 (1982).

    Article  CAS  Google Scholar 

  • Katz, B. and Miledi, R., Spontaneous and evoked activity of motor nerve endings in calcium Ringer, J. Physiol (Lond) 203: 689–706 (1969).

    CAS  Google Scholar 

  • Katz, B. and Miledi, R., Further study of the role of calcium in synaptic transmission, J. Physiol. (Lond) 207: 789–801 (1970).

    CAS  Google Scholar 

  • Kelly, P. T. and Cotman, C. W., Synaptic protein: characterization of tubulin and actin and identification of a distinct postsynaptic density protein, J. Cell Biol. 79: 173–183 (1978).

    Article  CAS  Google Scholar 

  • Kelly, P. T., McGuinness, T. L. and Greengard, P., Evidence that the major postsynaptic density protein is a component of a Ca2+ /calmodulindependent protein kinase, Proc. Natl. Acad. Sci. USA, 81: 945–949 (1984).

    Article  CAS  Google Scholar 

  • Kennedy, M., Experimental approaches to understanding the role of protein phosphorylation in the regulation of neuronal function, Ann. Rev. Neurosci. 6: 493–525 (1983).

    Article  CAS  Google Scholar 

  • Kennedy, M. B., Bennett, M. K. and Erondu, N. E., Biochemical and immunochemical evidence that the “major postsynaptic density protein” is a subunit of a calmodulin-dependent protein kinase, Proc. Natl. Acad. Sci. USA 80: 7357–7361 (1983).

    Article  CAS  Google Scholar 

  • Klee, C. B., Crouch, T. H. and Richman, P. G., Calmodulin, Ann. Rev. Biochem. 49: 489–515 (1980).

    Article  CAS  Google Scholar 

  • Larson, R. E., Goldenring, J. R., Vallano, M. L. and DeLorenzo, R. J., Identification of endogenous calmodulin-dependent kinase and calmodulin binding proteins in cold-stable microtubule preparations from rat brain, J. Neurochem. 44: 1566–1574 (1985).

    Article  CAS  Google Scholar 

  • Levitan, I. B., Lemos, J. R. and Novak-Hofer, I., Protein phosphorylation and the regulation of ion channels, Trends Neurosci. 6: 496–499 (1983).

    Article  CAS  Google Scholar 

  • Llinas, R., McGuinness, T. L., Leonard, C. S., Sugimori, M. and Greengard, P., Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse, Proc. Natl. Acad. Sci, USA 82: 3035–3039 (1985).

    Article  CAS  Google Scholar 

  • Matus, A., The postsynaptic density, Trends Neurosci. 4: 51–53 (1981).

    Article  Google Scholar 

  • McGuinness, T. L., Lai, Y., Greengard, P., Woodgett, J. R. and Cohen, P., A multifunctional calmodulin-dependent protein kinase, FEBS Lett., 163: 329–334 (1983).

    Article  CAS  Google Scholar 

  • McNamara, J. O., Selective alterations of regional beta-adrenergic receptor binding in the kindling model of epilepsy, Exp. Neurol. 61: 582–591 (1978).

    Article  CAS  Google Scholar 

  • Nestler, E. J. and Greengard, P., Protein phosphorylation in the brain, Nature 305: 583–588 (1983).

    Article  CAS  Google Scholar 

  • Nestler, E. J., Walaas, S. I. and Greengard, P., Neuronal phosphoproteins: Physiological and clinical implications, Science 225: 1357–1364 (1984).

    Article  CAS  Google Scholar 

  • Osterrieder, W., Brum, G., Hescheler, J., Trautwein, W., Flockerzi, V. and Hofmann, F., Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current, Nature 298: 576–578 (1982).

    Article  CAS  Google Scholar 

  • Ouimet, C. C., McGuinness, T. L. and Greengard, P., Immunocytochemical localization of calcium/calmodulin dependent protein kinase II in brain, Proc. Natl. Acad. Sci. USA 81: 5604–5608 (1984).

    Article  CAS  Google Scholar 

  • Racine, R. J., Kindling: The first decade, J. Neurosurg. 3: 234–252 (1978).

    Article  CAS  Google Scholar 

  • Rubin, R. P., The role of calcium in the release of neurotransmitter substances and hormones, Pharmacol. Rev. 22: 389–428 (1972).

    Google Scholar 

  • Sakakibara, M., Alkon, D. L., DeLorenzo, R. J., Goldenring, J. R., Neary, J. T. and Heldman, E., Modulating of calcium-mediated inactivation of ionic currents by Ca2+/calmodulin-dependent protein kinase II, Biophys. J., in press (1986).

    Google Scholar 

  • Schulman, H. and Greengard, P., Ca2+-dependent protein phosphorylation system in membranes from various tissues, and its activation by “calciumdependent regulator”, Proc. Natl. Acad. Sci. USA 75: 5432–5436 (1978a).

    Article  CAS  Google Scholar 

  • Schulman, H. and Greengard, P., Stimulation of brain membrane protein phosphorylation by calcium and an endogenous heat-stable protein, Nature 271: 478–479 (1978b).

    Article  CAS  Google Scholar 

  • Schulman, H., Phosphorylation of microtubule-associated proteins by a calcium/ calmodulin-dependent protein kinase, J Cell Biol 99: 15–21 (1984).

    Article  Google Scholar 

  • Siegelbaum, S. A., Camardo, J. S. and Kandel, E. R., Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones, Nature 299: 413–417 (1982).

    Article  CAS  Google Scholar 

  • Siegelbaum, S. A. and Tsien, R. W., Modulation of gated ion channels as a mode of transmitter action, Trends Neurosci. 6: 307–312 (1983).

    Article  CAS  Google Scholar 

  • Taft, W. C., Goldenring, J. R., Buckholz, T. M. and DeLorenzo, R. J., Benzodiazepine inhibition of purified CaM-dependent kinase, Pharmacologist 27: 185 (1985).

    Google Scholar 

  • Vallano, M. L., Buckholz, T. M. and DeLorenzo, R. J., Phosphorylation of neurofilament proteins by endogenous calcium/calmodulin dependent protein kinase, Biochem. Biophys. Res. Commun. 130: 957–963 (1985a).

    Article  CAS  Google Scholar 

  • Vallano, M. L., Goldenring, J. R., Buckholz, T. M., Larson, R. E. and DeLorenzo, R. J., Separation of endogenous calmodulin-and cAMP-dependent kinases from microtubule preparations, Proc. Natl. Acad. Sci. USA 82: 3203–3206 (1985b).

    Article  Google Scholar 

  • Wasterlain, C. G., Morin, A. M. and Jonec, V., Kindling: a pharmacological approach, Electroencephalog. Clin. Neurophysiol. 36: 264–273 (1982).

    CAS  Google Scholar 

  • Wasterlain, C. G. and Farber, D. B., Kindling alters the calcium/calmodulin-dependent phosphorylation of synaptic plasma membrane proteins in rat hippocampus, Proc. Natl. Acad. Sci. USA 81: 1225–1257 (1984).

    Article  Google Scholar 

  • Yamauchi, T. and Fujisawa, J., Purification and characterization of the brain calmodulin-dependent protein kinase (Kinase II), which is involved in the activation of tryptophan-5-mono-oxygenase, Eur. J. Biochem. 132: 15–21 (1983).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Neurology and Pharmacology, Medical College of Virginia - VCU, Richmond, Virginia, 23298, USA

    William C. Taft & Robert J. DeLorenzo

  2. Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    James R. Goldenring

Authors
  1. William C. Taft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James R. Goldenring
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert J. DeLorenzo
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The University of Vermont College of Medicine, Burlington, Vermont, USA

    Yigal H. Ehrlich , Robert H. Lenox  & Elizabeth Kornecki ,  & 

  2. Bolling A.F. Base, U.S. Air Force Office of Scientific Research, Washington, D.C., USA

    William O. Berry

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Plenum Press, New York

About this chapter

Cite this chapter

Taft, W.C., Goldenring, J.R., DeLorenzo, R.J. (1987). Molecular Mechanisms of Neuronal Excitability: Possible Involvement of CaM Kinase II in Seizure Activity. In: Ehrlich, Y.H., Lenox, R.H., Kornecki, E., Berry, W.O. (eds) Molecular Mechanisms of Neuronal Responsiveness. Advances in Experimental Medicine and Biology, vol 221. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7618-7_30

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-7618-7_30

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-7620-0

  • Online ISBN: 978-1-4684-7618-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation