Skip to main content

Organophosphorus Anticholinesterase-Induced Epileptiform Activity in the Hippocampus

  • Chapter

Abstract

In the study of epileptogenesis, the pharmacological induction of convulsant activity has provided important information regarding the cellular events involved in the production of abnormal electrical discharges. This research approach has benefited from the advent of in vitro central nervous system (CNS) tissue slices and the use of microelectrode recording techniques (Yamamoto, 1972). Synchronous repetitive discharges induced by the drugs examined thus far are the characteristic features of the epileptiform activity recorded in vivo and in vitro. These discharges are considered to be correlated with abnormal interictal electroencephalographic (EEG) recordings (Ayala et al., 1973). The corresponding intracellular event is comprised of a series of action potentials superimposed on an envelope of depolarization. This envelope of depolarization was termed the paroxysmal depolarizing shift (PDS) by Matsumoto and Ajmone Marson (196M) in characterizing penicillin-induced discharges in vivo. Recent studies have shown that the event underlying the drug-induced PDS is a net excitatory response produced by a synchronous synaptic input (Johnston and Brown, 1981; Lebeda et al., 1982).

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aldridge, W. N., 1953, The inhibition of erythrocyte cholinesterase by tri-esters of phosphoric acid. 3. The nature of the inhibitory process, Biochem. J, 54: 442–448.

    PubMed  CAS  Google Scholar 

  • Andersen, P., and Langmoen, I. A., 1980, Intracellular studies on transmitter effects on neurones in isolated brain slices, Q. Rev. Biophys, 13: 1–18.

    Article  PubMed  CAS  Google Scholar 

  • Ayala, G. F., Dichter, M., Gumnit, R. J., Matsumoto, H., and Spencer, W. A., 1973, Genesis of epileptic interictal spikes. New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysms, Brain Res, 52: 1–17.

    Article  PubMed  CAS  Google Scholar 

  • Bernardo, L. S., and Prince, D. A., 1981, Acetylcholine induced modulation of hippocampal pyramidal neurons, Brain Res, 211: 227–234.

    Article  Google Scholar 

  • Brimblecombe, R. W., 1974, “Drug Actions on Cholinergic Systems,” University Park Press, Baltimore.

    Google Scholar 

  • Brown, D. A., and Adams, P. R., 1980, Muscarinic suppression of a novel voltage-sensitive K current in a vertebrate neurone, Nature, 283: 673–676.

    Article  PubMed  CAS  Google Scholar 

  • Brown, T. H., and Johnston, D., 1983, Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurons, J. Neurophysiol, 50: 487–507.

    PubMed  CAS  Google Scholar 

  • Cole, A. E., and Nicoll, R. A., 1983, Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells, Science, 221: 1299–1301.

    Article  PubMed  CAS  Google Scholar 

  • Dingledine, R., and Gjerstad, L., 1980, Reduced inhibition during epileptiform activity in the in vitro hippocampal slice, J. Physiol. (Lond.), 305: 297–313.

    CAS  Google Scholar 

  • Ellin, R. I., 1982, Anomalies in theories and therapy of intoxication by potent organophosphorus anticholinesterase compounds, Gen. Pharmacol, 13: 457–466.

    Article  PubMed  CAS  Google Scholar 

  • Ellman, G. L., Courtney, K. D., Andres, V., and Featherstone, R. M., 1961, A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol, 7: 88–95.

    Article  PubMed  CAS  Google Scholar 

  • Haas, H. L., Schaerer, B., and Vosmansky, M., 1979, A simple perfusion chamber for the study of nervous tissue slices in vitro, J. Neurosci. Meth, 1: 323–325.

    Article  CAS  Google Scholar 

  • Halliwell, J. V., and Adams, P. R., 1982, Voltage-clamp analysis of muscarinic excitation in hippocampal neurons, Brain Res, 250: 71–92.

    Article  PubMed  CAS  Google Scholar 

  • Hampson, J. L., Essig, C. F., McCauley, A., and Himwich, H. E., 1950, Effects of di-isopropyl fluorophosphate (DFP) on electroencephalogram and cholinesterase activity, Electroencephalogr. Clin. Neurophysiol, 2: 41–48.

    Article  CAS  Google Scholar 

  • Harwood, C. T., 1954, Cholinesterase activity and electroencephalograms during circling induced by the intracarotid injection of di-isopropyl fluorophosphate (DFP), Amer. J. Physiol, 177: 171–174.

    PubMed  CAS  Google Scholar 

  • Johnston, D., 1981, Passive cable properties of hippocampal CA3 neurons, Cell. Mol. Neurobiol, 1: 45–55.

    Article  Google Scholar 

  • Johnston, D., and Brown, T. H., 1981, Giant synaptic potential hypothesis for epileptiform activity, Science, 211: 294–297.

    Article  PubMed  CAS  Google Scholar 

  • Johnston, D., and Brown, T. H., 1984, Biophysics and microphysiology of synaptic transmission in hippocampus, in: “Brain Slices,” R. Dingledine, ed., Plenum, New York.

    Google Scholar 

  • Johnston, D., Hablitz, J. J., and Wilson, W. A., 1980, Voltage clamp discloses slow inward current in hippocampal burst-firing neurones, Nature, 286: 391–393.

    Article  PubMed  CAS  Google Scholar 

  • Johnston, D., Rutecki, P. A., and Lebeda, F. J., Synaptic events underlying spontaneous and evoked paroxysmal discharges in hippocampal neurons, Plenum, New York, (in press).

    Google Scholar 

  • Karczmar, A. G., 1967, Pharmacologic, toxicologic, and therapeutic properties of anticholinesterase agents, In: “Physiological Pharmacology,” W. C. Root, and F. G. Hoffman, eds., Part C, Vol. 3, Academic Press, New York.

    Google Scholar 

  • Krnjevic, K., Pumain, R., and Renaud, L., 1971, The mechanism of excitation by acetylcholine in the cerebral cortex, J. Physiol. (Lond.), 215: 247–268.

    CAS  Google Scholar 

  • Krnjevic, K., Randic, M., and Straughan, D. W., 1966, Pharmacology of cortical inhibition, J. Physiol. (Lond.), 184: 78–105.

    CAS  Google Scholar 

  • Kuba, K., Albuquerque, E. X., Daly, J., and Barnard, E. A., 1974, A study of the irreversible cholinesterase inhibitor, diisopropylfluorophosphate, on time course of endplate currents in frog sartorius muscle, J. Pharmacol. Exp. Ther, 189: 499–512.

    PubMed  CAS  Google Scholar 

  • Lebeda, F. J., Hablitz, J. J., and Johnston, D., 1982, Antagonism of GABA-induced responses by d-tubocurarine in hippocampal neurons, J. Neurophysiol, 48: 622–632.

    PubMed  CAS  Google Scholar 

  • Lebeda, F. J., Rutecki, P. A., and Johnston, D., 1983, Synaptic mechanisms action of convulsion-producing anticholinesterases, Def. Tech. Info. Center, DA-300017, Alexandria, Virginia.

    Google Scholar 

  • Lebeda, F. J., and Rutecki, P. A, 1985, Characterization of spontaneous epileptiform discharges induced by organophosphorus anticholinesterases in the in vitro rat hippocampus, Proc. West. Pharmacol. Soc, 28: 187–190.

    PubMed  CAS  Google Scholar 

  • Lipp, J. A., 1972, Effect of diazepam upon soman-induced seizure activity and convulsions, Electroencephalogr. Clin. Neurqphysiol, 32: 557–560.

    CAS  Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., 1951, Protein measurement with Folin phenol reagent, J. Biol. Chem, 193: 265–275.

    PubMed  CAS  Google Scholar 

  • Machne, X., and Unna, K. R. W., 1963, Actions at the central nervous system, in: “Cholinesterases and Anticholinesterases,” G.B. Koelle, ed., ( Handbuch der Experimentellen Pharmakologie, Vol. 15 ), Springer-Verlag, Berlin.

    Google Scholar 

  • Main, A. R., 1964, Affinity and phosphorylation constants for the inhibition of esterases by organophosphates, Science, 144: 992–993.

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto, H., and Ajmone Marsan, C., 1964, Cortical cellular phenomena in experimental epilepsy: interictal manifestations, Exp. Neurol, 9: 286–304.

    Article  PubMed  CAS  Google Scholar 

  • O’Neill, J. J., 1981, Non-cholinesterase effects of anticholinesterases, Fundam. Appl. Pharmacol, 1: 154–160.

    Article  Google Scholar 

  • Rump, S., Grudzinska, E., and Edelwejn, Z., 1973, Effects of diazepam on epileptiform patterns of bioelectrical activity of the rabbit’s brain induced by fluostigmine, Neuropharmacology, 12: 813–817.

    Article  PubMed  CAS  Google Scholar 

  • Rutecki, P. A., Lebeda, F. J., and Johnston, D., 1984, Elevated extra-cellular potassium- and 4-aminopyridine-induced epileptiform activity in CA3 hippocampal neurons, Soc. Neurosci. Abstr, 10: 1.

    Google Scholar 

  • Rutecki, P. A., Lebeda, F. J., and Johnston, D., Epileptiform activity induced by changes in extracellular potassium in the hippocampus, J. Neurophysiol. (in press).

    Google Scholar 

  • Schwartzkroin, P. A., and Prince, D. A., 1980, Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity, Brain Res, 183: 61–73.

    Article  PubMed  CAS  Google Scholar 

  • Valentino, R. J., and Dingledine, R., 1981, Presynaptic inhibitory effect of acetylcholine in the hippocampus, J. Neurosci, 1: 784–792.

    PubMed  CAS  Google Scholar 

  • Van Meter, W. G., Karczmar, A. G., and Fiscus, R. R., 1978, CNS effects of anti-cholinesterases in the presence of inhibited cholinesterases, Arch. Int. Pharmacodyn, 231: 249–260.

    PubMed  Google Scholar 

  • Yamamoto, C.7 1972, Intracellular study of seizure-like afterdischarges elicited in thin hippocampal sections in vitro, Exp. Neurol, 35: 154–164.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Plenum Press, New York

About this chapter

Cite this chapter

Lebeda, F.J., Rutecki, P.A. (1987). Organophosphorus Anticholinesterase-Induced Epileptiform Activity in the Hippocampus. In: Dun, N.J., Perlman, R.L. (eds) Neurobiology of Acetylcholine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5266-2_35

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5266-2_35

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5268-6

  • Online ISBN: 978-1-4684-5266-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics