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. 1985 Aug;365:239–257. doi: 10.1113/jphysiol.1985.sp015769

Activity-dependent excitability changes in normal and demyelinated rat spinal root axons.

H Bostock, P Grafe
PMCID: PMC1192999  PMID: 4032313

Abstract

Myelinated nerve fibres with a reduced safety factor for conduction due to demyelination are easily blocked by trains of impulses. To find out why, in vivo recordings from rat ventral root fibres demyelinated with diphtheria toxin have been supplemented with in vivo and in vitro recordings from normal fibres. Despite a small rise in extracellular potassium activity, normal fibres were invariably hyperpolarized by intermittent trains of impulses. This hyperpolarization resulted in an increase in threshold and also in an enhancement of the depolarizing after-potential and the superexcitable period. Replacement of NaCl in the extracellular solution by LiCl completely blocked both the membrane hyperpolarization and the threshold increase which were normally observed during intermittent trains of impulses. At demyelinated nodes which were blocked by trains of impulses (10-50 Hz), conduction block was preceded by a rise in threshold current and in an increase in internodal conduction time, but by no detectable reduction in the outward current generated by the preceding node. It was found possible to prevent the threshold from changing during a train by automatic adjustment of a d.c. polarizing current. This 'threshold clamp' prevented the conduction failure and virtually abolished the changes in internodal conduction time. The threshold changes were attributed to hyperpolarization, as in normal fibres, since (a) the polarizing current required to prevent them was always a depolarizing current, and (b) they were accompanied by an increase in superexcitability. The post-tetanic depression that can follow continuous trains of impulses was attributed to the combination of increased threshold and enhanced superexcitable period due to hyperpolarization. It is concluded that the susceptibility of these demyelinated fibres to impulse trains is not due to a membrane depolarization induced by extracellular potassium accumulation but to a membrane hyperpolarization as a consequence of electrogenic sodium pumping.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adrian E. D. On the summation of propagated disturbances in nerve and muscle. J Physiol. 1912 Mar 29;44(1-2):68–124. doi: 10.1113/jphysiol.1912.sp001503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ballanyi K., Grafe P., ten Bruggencate G. Intracellular free sodium and potassium, post-carbachol hyperpolarization, and extracellular potassium-undershoot in rat sympathetic neurones. Neurosci Lett. 1983 Aug 8;38(3):275–279. doi: 10.1016/0304-3940(83)90381-6. [DOI] [PubMed] [Google Scholar]
  3. Barrett E. F., Barrett J. N. Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential. J Physiol. 1982 Feb;323:117–144. doi: 10.1113/jphysiol.1982.sp014064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bergman J., Dubois J. M., Bergman C. Post-tetanic membrane potential in single axon and myelinated nerve trunk. Ann N Y Acad Sci. 1980;339:21–38. doi: 10.1111/j.1749-6632.1980.tb15965.x. [DOI] [PubMed] [Google Scholar]
  5. Bostock H., Sears T. A., Sherratt R. M. The spatial distribution of excitability and membrane current in normal and demyelinated mammalian nerve fibres. J Physiol. 1983 Aug;341:41–58. doi: 10.1113/jphysiol.1983.sp014791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bostock H., Sears T. A. The internodal axon membrane: electrical excitability and continuous conduction in segmental demyelination. J Physiol. 1978 Jul;280:273–301. doi: 10.1113/jphysiol.1978.sp012384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bostock H., Sherratt R. M., Sears T. A. Overcoming conduction failure in demyelinated nerve fibres by prolonging action potentials. Nature. 1978 Jul 27;274(5669):385–387. doi: 10.1038/274385a0. [DOI] [PubMed] [Google Scholar]
  8. Brismar T. Specific permeability properties of demyelinated rat nerve fibres. Acta Physiol Scand. 1981 Oct;113(2):167–176. doi: 10.1111/j.1748-1716.1981.tb06878.x. [DOI] [PubMed] [Google Scholar]
  9. Davis F. A. Impairment of repetitive impulse conduction in experimentally demyelinated and pressure-injured nerves. J Neurol Neurosurg Psychiatry. 1972 Aug;35(4):537–544. doi: 10.1136/jnnp.35.4.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davis F. A., Schauf C. L. Approaches to the development of pharmacological interventions in multiple sclerosis. Adv Neurol. 1981;31:505–510. [PubMed] [Google Scholar]
  11. ECCLES J. C., KRNJEVIC K. Potential changes recorded inside primary afferent fibres within the spinal cord. J Physiol. 1959 Dec;149:250–273. doi: 10.1113/jphysiol.1959.sp006338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grafe P., Reddy M. M., Emmert H., ten Bruggencate G. Effects of lithium on electrical activity and potassium ion distribution in the vertebrate central nervous system. Brain Res. 1983 Nov 21;279(1-2):65–76. doi: 10.1016/0006-8993(83)90163-4. [DOI] [PubMed] [Google Scholar]
  13. Grafe P., Rimpel J., Reddy M. M., ten Bruggencate G. Lithium distribution across the membrane of motoneurons in the isolated frog spinal cord. Pflugers Arch. 1982 Jun;393(4):297–301. doi: 10.1007/BF00581413. [DOI] [PubMed] [Google Scholar]
  14. Hille B. The permeability of the sodium channel to metal cations in myelinated nerve. J Gen Physiol. 1972 Jun;59(6):637–658. doi: 10.1085/jgp.59.6.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kocsis J. D., Malenka R. C., Waxman S. G. Effects of extracellular potassium concentration on the excitability of the parallel fibres of the rat cerebellum. J Physiol. 1983 Jan;334:225–244. doi: 10.1113/jphysiol.1983.sp014491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koles Z. J., Rasminsky M. A computer simulation of conduction in demyelinated nerve fibres. J Physiol. 1972 Dec;227(2):351–364. doi: 10.1113/jphysiol.1972.sp010036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Low P. A., McLeod J. G. Refractory period, conduction of trains of impulses, and effect of temperature on conduction in chronic hypertrophic neuropathy. J Neurol Neurosurg Psychiatry. 1977 May;40(5):434–447. doi: 10.1136/jnnp.40.5.434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Malenka R. C., Kocsis J. D., Waxman S. G. The supernormal period of the cerebellar parallel fibers effects of [Ca2+]o and [K+]o. Pflugers Arch. 1983 May;397(3):176–183. doi: 10.1007/BF00584354. [DOI] [PubMed] [Google Scholar]
  19. McDonald W. I., Sears T. A. The effects of experimental demyelination on conduction in the central nervous system. Brain. 1970;93(3):583–598. doi: 10.1093/brain/93.3.583. [DOI] [PubMed] [Google Scholar]
  20. Rasminsky M., Sears T. A. Internodal conduction in undissected demyelinated nerve fibres. J Physiol. 1972 Dec;227(2):323–350. doi: 10.1113/jphysiol.1972.sp010035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raymond S. A. Effects of nerve impulses on threshold of frog sciatic nerve fibres. J Physiol. 1979 May;290(2):273–303. doi: 10.1113/jphysiol.1979.sp012771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schauf C. L., Davis F. A. Impulse conduction in multiple sclerosis: a theoretical basis for modification by temperature and pharmacological agents. J Neurol Neurosurg Psychiatry. 1974 Feb;37(2):152–161. doi: 10.1136/jnnp.37.2.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schoepfle G. M., Katholi C. R. Posttetanic changes in membrane potential of single medullated nerve fibers. Am J Physiol. 1973 Dec;225(6):1501–1507. doi: 10.1152/ajplegacy.1973.225.6.1501. [DOI] [PubMed] [Google Scholar]
  24. Thomas R. C. Electrogenic sodium pump in nerve and muscle cells. Physiol Rev. 1972 Jul;52(3):563–594. doi: 10.1152/physrev.1972.52.3.563. [DOI] [PubMed] [Google Scholar]
  25. Waxman S. G. Clinicopathological correlations in multiple sclerosis and related diseases. Adv Neurol. 1981;31:169–182. [PubMed] [Google Scholar]

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