Skip to main content
Log in

Acute stages of batrachotoxin-induced neuropathy: a morphologic study of a sodium-channel toxin

  • Published:
Journal of Neurocytology

Summary

The acute effects of batrachotoxin, a steroidal neurotoxin which opens the membrane sodium channel, were observed morphologically at various time points up to 3 h after injection into rat peroneal nerve. Three changes were found. First, there was massive swelling of the axon at the node of Ranvier accompanied by retraction of paranodal myelin. Second, a similar swelling of unmyelinated axons was seen. Third, extracellular fluid accumulated along the internode in the adaxonal space, the intraperiod line of myelin and, rarely, the external mesaxon, with concomitant shrinkage of the axon. The first two changes might be explained on the basis of massive shift of sodium through the batrachotoxin-modified sodium channel into the axon and subsequent osmotic shift of fluid. The reason for the third change is not clear but probably also has a ionic basis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albuquerque, E. X. (1972) The mode of action of batrachotoxin.Federation Proceedings 31, 1133–8.

    Google Scholar 

  • Albuquerque, E. X., Daly, J. W. &Witkop, B. (1971) Batrachotoxin: chemistry and pharmacology.Science 172, 995–1002.

    Google Scholar 

  • Allen, C. N., Akaike, A. &Albuquerque, E. X. (1984) The frog interosseal muscle fiber as a new model for patch clamp studies of chemosensitive- and voltage-sensitive ion channels: actions of acetylcholine and batrachotoxin.Journal de Physiologie (Paris)79, 338–43.

    Google Scholar 

  • Baker, M., Bostock, H., Brook, G. A. &Love, S. (1985)Phoneutria andLeiurus venoms induce spontaneous compound action potentials in rat spinal roots.Journal of Physiology 369, 63P.

    Google Scholar 

  • Barrett, E. F. &Barrett, J. N. (1982) Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential.Journal of Physiology 323, 117–44.

    Google Scholar 

  • Blank, W. F., Bunge, M. B. &Bunge, R. P. (1974) The sensitivity of the myelin sheath, particularly the Schwann cell-axolemmal junction, to lowered calcium levels in cultured sensory ganglia.Brain Research 67, 503–18.

    Google Scholar 

  • Boegman, R. J. &Albuquerque, E. X. (1978) Batrachotoxin blocks fast axon transportin vivo.Federation Proceedings 37, 525.

    Google Scholar 

  • Boegman, R. J., Deshpande, S. S. &Albuquerque, E. X. (1980) Consequences of axonal transport blockade induced by batrachotoxin on mammalian neuromuscular junction. I. Early pre- and post-synaptic changes.Brain Research 187, 183–96.

    Google Scholar 

  • Boegman, R. J. &Riopelle, R. J. (1980) Batrachotoxin blocks slow and retrograde axonal transportin vivo.Neuroscience Letters 18, 143–7.

    Google Scholar 

  • Carafoli, E. &Crompton, M. (1978) The regulation of intracellular calcium. InCurrent Topics in Membranes and Transport. Membrane Properties: Mechanical Aspects, Receptors, Energetics and Calcium-Dependence of Transport, Vol. 10 (edited byBronner, F. &Kleinzeller, A.) pp. 151–216. New York: Academic Press.

    Google Scholar 

  • Carafoli, E., Tiozzo, R., Lugli, G., Crovetti, F. &Kratzing, C. (1974) The release of calcium from heart mitochondria by sodium.Journal of Molecular and Cellular Cardiology 6, 361–71.

    Google Scholar 

  • Chiu, S. Y., Schräger, P. &Ritchie, J. M. (1984) Neuronal-type Na+ and K+ channels in rabbit cultured Schwann cells.Nature 311, 156–7.

    Google Scholar 

  • Deshpande, S. S., Boegman, R. J. &Albuquerque, E. X. (1981) Consequences of axonal transport blockade by batrachotoxin on mammalian neuromuscular junction. II. Late pre- and post-synaptic changes.Brain Research 225, 115–29.

    Google Scholar 

  • Friede, R. L. &Bischhausen, R. (1978) How do axons control myelin formation? The model of 6-aminonicotinamide neuropathy.Journal of the Neurological Sciences 35, 341–53.

    Google Scholar 

  • Hall, S. M. &Williams, P. L. (1971) The distribution of electron-dense tracers in peripheral nerve fibres.Journal of Cell Science 8, 541–55.

    Google Scholar 

  • Hirano, A. (1983) Reaction of the periaxonal space to some pathologic processes. InProgress in Neuropathology Vol. 5, (edited byZimmerman, H. M.), pp. 99–112. New York: Raven Press.

    Google Scholar 

  • Hirano, A. &Dembitzer, H. M. (1981) The periaxonal space in an experimental model of neuropathy: the mutant Syrian hamster with hindleg paralysis.Journal of Neurocytology 10, 261–9.

    Google Scholar 

  • Huang, L-J. M., Moran, N. &Ehrenstein, G. (1982) Batrachotoxin modifies the gating kinetics of sodium channels in internally perfused neuroblastoma cells.Proceedings of the National Academy of Sciences USA 79, 2082–5.

    Google Scholar 

  • Huang, L-J. M., Moran, N. &Ehrenstein, G. (1984) Gating kinetics of batrachotoxin-modified sodium channels in neuroblastoma cells determined from single-channel measurements.Biophysical Journal 45, 313–22.

    Google Scholar 

  • Hudson, C. S., Deshpande, S. S. &Albuquerque, E. X. (1984) Consequences of axonal transport blockade by batrachotoxin on mammalian neuromuscular junction. III. An ultrastructural study.Brain Research 296, 319–32.

    Google Scholar 

  • Jacobs, J. M., Miller, R. H., Whittle, A. &Cavanagh, J. B. (1979) Studies on the early changes in acute isoniazid neuropathy in the rat.Acta neuropathologica (Berlin)47, 85–92.

    Google Scholar 

  • Karnovsky, M. J. (1965) A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy.Journal of Cell Biology 27, 137A-138A.

    Google Scholar 

  • Khodorov, B. I. &Revenko, S. V. (1979) Further analysis of the mechanisms of action of batrachotoxin on the membrane of myelinated nerve.Neuroscience 4, 1315–30.

    Google Scholar 

  • Krueger, B. K., French, R. J., Blaustein, M. B. &Worley, J. F. III (1982) Incorporation of Ca++ activated K+ channels, from rat brain, into planar iipid bilayers.Biophysical Journal 37, 170a.

    Google Scholar 

  • Latorre, R. &Miller, C. (1983) Conduction and selectivity in potassium channels.Journal of Membrane Biology 71, 11–30.

    Google Scholar 

  • Love, S., Cruz-Höfling, M. A. &Duchen, L. W. (1986) Morphological abnormalities in myelinated nerve fibres caused byLeiurus, Centruroides andPhoneutria venoms and their prevention by tetrodotoxin.Quarterly Journal of Experimental Physiology 71, 115–22.

    Google Scholar 

  • Meves, H., Rubly, N. &Watt, D. D. (1982) Effect of toxins isolated from the venom of the scorpionCentruroides sculptumtus on the Na currents of the node of Ranvier.Pflügers Archiv 393, 56–62.

    Google Scholar 

  • Moore, G. R. W., Boegman, R. J., Robertson, D. M. &Riopelle, R. J. (1981) Batrachotoxin induced axonal necrosis in peripheral nerves.Brain Research 207, 481–5.

    Google Scholar 

  • Moore, G. R. W., Robertson, D. M. &Boegman, R. J. (1983) Batrachotoxin induced axonal necrosis followed by regeneration.Brain Research 279, 246–9.

    Google Scholar 

  • Moore, J. W. (1978) On sodium conductance gates in nerve membranes. InPhysiology and Pathobiology of Axons (edited byWaxman, S. G.), pp. 145–53. New York: Raven Press.

    Google Scholar 

  • Ochs, S. &Worth, R. (1975) Batrachotoxin block of fast axoplasmic transport in mammalian nerve fibers.Science 187, 1087–9.

    Google Scholar 

  • Quandt, F. M. &Narahashi, T. (1982) Modification of single Na+ channels by batrachotoxin.Proceedings of the National Academy of Sciences USA 79, 6732–6.

    Google Scholar 

  • Raine, C. S. (1982) Differences between the nodes of Ranvier of large and small diameter fibres in the P.N.S.Journal of Neurocytology 11, 935–47.

    Google Scholar 

  • Robertson, J. D. (1958) Structural alterations in nerve fibers produced by hypotonic and hypertonic solutions.Journal of Biophysical and Biochemical Cytology 4, 349–64.

    Google Scholar 

  • Shrager, P., Chiu, S. Y. &Ritchie, J. M. (1985) Voltage-dependent sodium and potassium channels in mammalian cultured Schwann cells.Proceedings of the National Academy of Sciences USA 82, 948–52.

    Google Scholar 

  • Spencer, P. S., Peterson, E. R., Madrid, A. R. &Raine, C. S. (1973) Effects of thallium salts on neuronal mitochondria in organotypic cord-ganglia-muscle combination cultures.Journal of Cell Biology 58, 79–95.

    Google Scholar 

  • Waxman, S. G. &Ritchie, J. M. (1985) Organization of ion channels in the myelinated nerve fiber.Science 228, 1502–7.

    Google Scholar 

  • Worth, R. M. &Ochs, S. (1982) Dependence of batrachotoxin block of axoplasmic transport on sodium.Journal of Neurobiology 13, 537–49.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moore, G.R.W., Boegman, R.J., Robertson, D.M. et al. Acute stages of batrachotoxin-induced neuropathy: a morphologic study of a sodium-channel toxin. J Neurocytol 15, 573–583 (1986). https://doi.org/10.1007/BF01611858

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01611858

Keywords

Navigation