Abstract
Clinical and laboratory observations both suggest that it may be possible for action potentials to traverse, in a continuous manner and without interruption, demyelinated zones along some axons. This continuous mode of conduction requires the presence of sufficient numbers of sodium channels in the demyelinated region. One of the factors which will tend to prevent such conduction is the impedance mismatch at sites of focal demyelination, which may result in a reduction in current density sufficient to cause conduction failure. As part of an effort to examine the conditions which would promote conduction into, and beyond, the demyelinated region, we examined, using computer simulations, the effects of reduction in length of the proximal internodes closest to the demyelinated region. Our results indicate that reduction in length of the two internodes closest to the demyelinated region. to approximately one-third of normal length or less, will facilitate conduction beyond the plaque. The results suggest that reductions in internode length, which have been histologically observed along some demyelinated fibres, may have functional significance in terms of facilitating conduction past focally demyelinated zones.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bostock H., Sears T. A. Continuous conduction in demyelinated mammalian nerve fibers. Nature. 1976 Oct 28;263(5580):786–787. doi: 10.1038/263786a0. [DOI] [PubMed] [Google Scholar]
- Brill M. H., Waxman S. G., Moore J. W., Joyner R. W. Conduction velocity and spike configuration in myelinated fibres: computed dependence on internode distance. J Neurol Neurosurg Psychiatry. 1977 Aug;40(8):769–774. doi: 10.1136/jnnp.40.8.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis F. A., Jacobson S. Altered thermal sensitivity in injured and demyelinated nerve. A possible model of temperature effects in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1971 Oct;34(5):551–561. doi: 10.1136/jnnp.34.5.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FITZHUGH R. Computation of impulse initiation and saltatory conduction in a myelinated nerve fiber. Biophys J. 1962 Jan;2:11–21. doi: 10.1016/s0006-3495(62)86837-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gledhill R. F., Harrison B. M., McDonald W. I. Pattern of remyelination in the CNS. Nature. 1973 Aug 17;244(5416):443–444. doi: 10.1038/244443a0. [DOI] [PubMed] [Google Scholar]
- Goldstein S. S., Rall W. Changes of action potential shape and velocity for changing core conductor geometry. Biophys J. 1974 Oct;14(10):731–757. doi: 10.1016/S0006-3495(74)85947-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halliday A. M., McDonald W. I., Mushin J. Visual evoked response in diagnosis of multiple sclerosis. Br Med J. 1973 Dec 15;4(5893):661–664. doi: 10.1136/bmj.4.5893.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halliday A. M., McDonald W. I. Pathophysiology of demyelinating disease. Br Med Bull. 1977 Jan;33(1):21–27. doi: 10.1093/oxfordjournals.bmb.a071390. [DOI] [PubMed] [Google Scholar]
- Khodorov B. I., Timin E. N., Vilenkin S. Ia, Gul'ko F. B. Teoreticheskii analiz mekhanizmov provedeniia nervnogo impul&sa po neodnorodnomu aksonu. I. Provedenie cherez uchastok s uveilichennym diametrom. Biofizika. 1969 Mar-Apr;14(2):304–315. [PubMed] [Google Scholar]
- 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]
- Moore J. W., Joyner R. W., Brill M. H., Waxman S. D., Najar-Joa M. Simulations of conduction in uniform myelinated fibers. Relative sensitivity to changes in nodal and internodal parameters. Biophys J. 1978 Feb;21(2):147–160. doi: 10.1016/S0006-3495(78)85515-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore J. W., Ramón F., Joyner R. W. Axon voltage-clamp simulations. I. Methods and tests. Biophys J. 1975 Jan;15(1):11–24. doi: 10.1016/S0006-3495(75)85788-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Namerow N. S., Thompson L. R. Plaques, symptoms, and the remitting course of multiple sclerosis. Neurology. 1969 Aug;19(8):765–774. doi: 10.1212/wnl.19.8.765. [DOI] [PubMed] [Google Scholar]
- Parnas I., Hochstein S., Parnas H. Theoretical analysis of parameters leading to frequency modulation along an inhomogeneous axon. J Neurophysiol. 1976 Jul;39(4):909–923. doi: 10.1152/jn.1976.39.4.909. [DOI] [PubMed] [Google Scholar]
- Ramón F., Joyner R. W., Moore J. W. Propagation of action potentials in inhomogeneous axon regions. Fed Proc. 1975 Apr;34(5):1357–1363. [PubMed] [Google Scholar]
- 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]
- Rasminsky M. The effects of temperature on conduction in demyelinated single nerve fibers. Arch Neurol. 1973 May;28(5):287–292. doi: 10.1001/archneur.1973.00490230023001. [DOI] [PubMed] [Google Scholar]
- Ritchie J. M., Rogart R. B. Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath. Proc Natl Acad Sci U S A. 1977 Jan;74(1):211–215. doi: 10.1073/pnas.74.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Suzuki K., Andrews J. M., Waltz J. M., Terry R. D. Ultrastructural studies of multiple sclerosis. Lab Invest. 1969 May;20(5):444–454. [PubMed] [Google Scholar]
- Waxman S. G. Closely spaced nodes of Ranvier in the teleost brain. Nature. 1970 Jul 18;227(5255):283–284. doi: 10.1038/227283a0. [DOI] [PubMed] [Google Scholar]
- Waxman S. G. Integrative properties and design principles of axons. Int Rev Neurobiol. 1975;18:1–40. doi: 10.1016/s0074-7742(08)60032-x. [DOI] [PubMed] [Google Scholar]
- Waxman S. G. Regional differentiation of the axon: a review with special reference to the concept of the multiplex neuron. Brain Res. 1972 Dec 12;47(2):269–288. doi: 10.1016/0006-8993(72)90639-7. [DOI] [PubMed] [Google Scholar]