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Conduction in Myelinated, Unmyelinated, and Demyelinated Fibers

Conduction in Myelinated, Unmyelinated, and Demyelinated Fibers Abstract • Conduction in demyelinated axons is characterized by decreased conduction velocity, temporal dispersion of impulses, and conduction failure. It is not possible to infer the electrical properties of the bared internodal axon membrane in demyelinated fibers from observations of decreased conduction velocity or conduction failure. Cytochemical evidence indicates that there are, in fact, distinct structural differences between nodal and internodal regions of the normal axon membrane. This conclusion is confirmed by freeze-fracture and pharmacological studies. A number of approaches to the development of effective symptomatic therapy in the demyelinating diseases are suggested by recent experimental findings: determination of the membrane properties necessary for conduction across focally demyelinated regions and the identification of agents that would encourage the development of these properties; alterations in the external milieu of demyelinated fibers; and the development of agents that might promote remyelination. References 1. McDonald WI: The effects of experimental demyelination on conduction in peripheral nerve: A histological and electrophysiological study: II. Electrophysiological observations . Brain 86:501-524, 1963.Crossref 2. Mayer RF, Denny-Brown D: Conduction velocity in peripheral nerve during experimental demyelination in the cat . Neurology 14:714-726, 1964.Crossref 3. Hall JL: Studies on demyelinated peripheral nerves in guinea pigs with experimental allergic neuritis: A histological and electrophysiological study: II. Electrophysiological observations . Brain 90:313-332, 1967.Crossref 4. McDonald WI, Sears TA: The effects of experimental demyelination on conduction in the central nervous system . Brain 93:583-598, 1970.Crossref 5. Mayer RF: Conduction velocity in the central nervous system of the cat during experimental demyelination and remyelination . Int J Neurosci 1:287-308, 1971.Crossref 6. Rasminsky M, Sears TA: Internodal conduction in undissected demyelinated nerve fibers . J Physiol 227:323-350, 1972. 7. Gilliatt RW, Willison RG: Peripheral nerve conduction in diabetic neuropathy . J Neurol Neurosurg Psychiatry 25:11-18, 1962.Crossref 8. McDonald WI: Pathophysiology in multiple sclerosis . Brain 97:179-196, 1974.Crossref 9. Davis FA: Impairment of repetitive impulse conduction in experimentally demyelinated and pressure-injured nerves . J Neurol Neurosurg Psychiatry 35:537-544, 1972.Crossref 10. Waxman SG: Integrative properties and design principles of axons . Int Rev Neurobiol 18:1-40, 1975. 11. Davis FA, Schauf CL: The pathophysiology of multiple sclerosis: A theoretical model , in Klawans HL (ed): Models of Human Neurological Diseases . Amsterdam, Excerpta Medica, 1974. 12. Waxman SG, Brill MH, Geschwind N, et al: Probability of conduction deficit as related to fiber length in random-distribution models of peripheral neuropathies . J Neurol Sci 29:39-53, 1976.Crossref 13. Huizar P, Kuno M, Miyata Y: Electrophysiological properties of spinal motoneurones of normal and dystrophic mice . J Physiol 248:231-246, 1975. 14. Tasaki I, Freygang WH Jr: The parallelism between the action potential, action current, and membrane resistance at a node of Ranvier . J Gen Physiol 39:211-223, 1955.Crossref 15. Katz B, Miledi R: Propagation of electric activity in motor nerve terminals . Proc R Soc Lond (Biol) 161:453-482, 1965.Crossref 16. Koles ZJ, Rasminsky M: A computer simulation of conduction in demyelinated nerve fibres . J Physiol 227:351-364, 1972. 17. Huxley AF, Stämpfli R: Evidence for saltatory conduction in peripheral myelinated nerve fibres . J Physiol 108:315-339, 1949. 18. Quick DC, Waxman SG: Specific staining of the axon membrane at nodes of Ranvier with ferric ion and ferrocyanide . J Neurol Sci 31:1-11, 1977.Crossref 19. Waxman SG, Quick DC: Cytochemical differentiation of the axon membrane in A- and C-fibers . J Neurol Neurosurg Psychiatry 40:379-385, 1977.Crossref 20. Bennett MLV: Comparative physiology: Electric organs . Ann Rev Physiol 32:471-528, 1970.Crossref 21. Waxman SG, Pappas GD, Bennett MVL: Morphological correlates of functional differentiation of nodes of Ranvier along single fibers in the neurogenic electric organ of the knife fish Sternarchus . J Cell Biol 53:210-224, 1972.Crossref 22. Rosenbluth J: Intramembranous particle distribution at the node of Ranvier and adjacent axolemma in myelinated axons of the frog brain . J Neurocytol 5:731-745, 1976.Crossref 23. Kristol C, Akert K, Sandri C, et al: The Ranvier nodes in the neurogenic electric organ of the knifefish Sternarchus: A freeze-etching study on the distribution of membrane-associated particles . Brain Res 125:197-212, 1977.Crossref 24. Ritchie JM, Rogart RB: The density of sodium channels in mammalian myelinated nerve fibers and the nature of the axonal membrane under the myelin sheath . Proc Natl Acad Sci USA 74:211-215, 1977.Crossref 25. Nonner W, Rojas E, Stämpfli R: Gating currents in the node of Ranvier: Voltage and time dependence . Philos Trans R Soc Lond (Biol) 270:483-492, 1975.Crossref 26. Ritchie JM, Rogart RB, Strichartz G: A new method for labeling saxitoxin and its binding to non-myelinated fibres of the rabbit vagus, lobster walking, and garfish olfactory nerves . J Physiol 261:477-494, 1976. 27. Bostock H, Sears TA: Continuous conduction in demyelinated mammalian nerve fibres . Nature 263:786-787, 1976.Crossref 28. Rasminsky M, Kearney RE: Continuous conduction in large diameter bare axons in spinal roots of dystrophic mice . Neurology 26:367, 1976. 29. MacKay RP, Hirano A: Forms of benign multiple sclerosis: Report of two clinically silent cases discovered at autopsy . Arch Neurol 17:588-600, 1967.Crossref 30. Namerow NS, Thompson LR: Plaques, symptoms, and the remitting course of multiple sclerosis . Neurology 19:765-774, 1969.Crossref 31. Ghatak NR, Hirano A, Lijtmaer H, et al: Asymptomatic demyelinated plaque in the spinal cord . Arch Neurol 30:484-486, 1974.Crossref 32. Wisniewski H, Oppenheimer D, McDonald WI: Relation between myelination and function in MS and EAE . J Neuropathol Exp Neurol 35:327, 1976.Crossref 33. Sidman RL, Green MC, Appel SH: Catalog of the Neurological Mutants of the Mouse . Cambridge, Harvard University Press, 1965. 34. Simons DJ: A note on the effect of heat and cold upon certain symptoms of multiple sclerosis . Bull Neurol Inst NY 6:385-386, 1937. 35. Guthrie TC: Visual and motor changes in patients with multiple sclerosis: A result of induced changes in environmental temperature . Arch Neurol Psychiatry 65:437-451, 1951.Crossref 36. Davis FA, Jacobson S: Altered thermal sensitivity in injured and demyelinated nerve . J Neurol Neurosurg Psychiatry 34:551-561, 1971.Crossref 37. Rasminsky M: The effects of temperature on conduction in demyelinated single nerve fibers . Arch Neurol 28:287-292, 1973.Crossref 38. Davis FA, Becker FO, Michael JA, et al: Effect of intravenous sodium bicarbonate, disodium edetate (Na2EDTA), and hyperventilation on visual and oculomotor signs in multiple sclerosis . J Neurol Neurosurg Psychiatry 33:723-732, 1970.Crossref 39. Becker FO, Michael JA, Davis FA: Acute effects of oral phosphate on visual function in multiple sclerosis . Neurology 24:601-607, 1974.Crossref 40. Harrison BM, McDonald WI, Ochoa J: Remyelination in the central diphtheria toxin lesion . J Neurol Sci 17:293-302, 1972.Crossref 41. Suzuki K, Andrews JM, Waltz JM, et al: Ultrastructural studies of multiple sclerosis . Lab Invest 20:444-454, 1969. 42. Gledhill RF, Harrison BM, McDonald WI: Pattern of remyelination in the CNS . Nature 244:443-444, 1973.Crossref 43. Brill MH, Waxman SG, Moore JW, et al: Conduction velocity and spike configuration in myelinated fibers: Computed dependence on internode distance . J Neurol Neurosurg Psychiatry , to be published. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Conduction in Myelinated, Unmyelinated, and Demyelinated Fibers

Waxman, Stephen G.
Archives of Neurology , Volume 34 (10) – Oct 1, 1977
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References (48)

Publisher
American Medical Association
Copyright
Copyright © 1977 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1977.00500220019003
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Abstract

Abstract • Conduction in demyelinated axons is characterized by decreased conduction velocity, temporal dispersion of impulses, and conduction failure. It is not possible to infer the electrical properties of the bared internodal axon membrane in demyelinated fibers from observations of decreased conduction velocity or conduction failure. Cytochemical evidence indicates that there are, in fact, distinct structural differences between nodal and internodal regions of the normal axon membrane. This conclusion is confirmed by freeze-fracture and pharmacological studies. A number of approaches to the development of effective symptomatic therapy in the demyelinating diseases are suggested by recent experimental findings: determination of the membrane properties necessary for conduction across focally demyelinated regions and the identification of agents that would encourage the development of these properties; alterations in the external milieu of demyelinated fibers; and the development of agents that might promote remyelination. References 1. McDonald WI: The effects of experimental demyelination on conduction in peripheral nerve: A histological and electrophysiological study: II. Electrophysiological observations . Brain 86:501-524, 1963.Crossref 2. Mayer RF, Denny-Brown D: Conduction velocity in peripheral nerve during experimental demyelination in the cat . Neurology 14:714-726, 1964.Crossref 3. Hall JL: Studies on demyelinated peripheral nerves in guinea pigs with experimental allergic neuritis: A histological and electrophysiological study: II. Electrophysiological observations . Brain 90:313-332, 1967.Crossref 4. McDonald WI, Sears TA: The effects of experimental demyelination on conduction in the central nervous system . Brain 93:583-598, 1970.Crossref 5. Mayer RF: Conduction velocity in the central nervous system of the cat during experimental demyelination and remyelination . Int J Neurosci 1:287-308, 1971.Crossref 6. Rasminsky M, Sears TA: Internodal conduction in undissected demyelinated nerve fibers . J Physiol 227:323-350, 1972. 7. Gilliatt RW, Willison RG: Peripheral nerve conduction in diabetic neuropathy . J Neurol Neurosurg Psychiatry 25:11-18, 1962.Crossref 8. McDonald WI: Pathophysiology in multiple sclerosis . Brain 97:179-196, 1974.Crossref 9. Davis FA: Impairment of repetitive impulse conduction in experimentally demyelinated and pressure-injured nerves . J Neurol Neurosurg Psychiatry 35:537-544, 1972.Crossref 10. Waxman SG: Integrative properties and design principles of axons . Int Rev Neurobiol 18:1-40, 1975. 11. Davis FA, Schauf CL: The pathophysiology of multiple sclerosis: A theoretical model , in Klawans HL (ed): Models of Human Neurological Diseases . Amsterdam, Excerpta Medica, 1974. 12. Waxman SG, Brill MH, Geschwind N, et al: Probability of conduction deficit as related to fiber length in random-distribution models of peripheral neuropathies . J Neurol Sci 29:39-53, 1976.Crossref 13. Huizar P, Kuno M, Miyata Y: Electrophysiological properties of spinal motoneurones of normal and dystrophic mice . J Physiol 248:231-246, 1975. 14. Tasaki I, Freygang WH Jr: The parallelism between the action potential, action current, and membrane resistance at a node of Ranvier . J Gen Physiol 39:211-223, 1955.Crossref 15. Katz B, Miledi R: Propagation of electric activity in motor nerve terminals . Proc R Soc Lond (Biol) 161:453-482, 1965.Crossref 16. Koles ZJ, Rasminsky M: A computer simulation of conduction in demyelinated nerve fibres . J Physiol 227:351-364, 1972. 17. Huxley AF, Stämpfli R: Evidence for saltatory conduction in peripheral myelinated nerve fibres . J Physiol 108:315-339, 1949. 18. Quick DC, Waxman SG: Specific staining of the axon membrane at nodes of Ranvier with ferric ion and ferrocyanide . J Neurol Sci 31:1-11, 1977.Crossref 19. Waxman SG, Quick DC: Cytochemical differentiation of the axon membrane in A- and C-fibers . J Neurol Neurosurg Psychiatry 40:379-385, 1977.Crossref 20. Bennett MLV: Comparative physiology: Electric organs . Ann Rev Physiol 32:471-528, 1970.Crossref 21. Waxman SG, Pappas GD, Bennett MVL: Morphological correlates of functional differentiation of nodes of Ranvier along single fibers in the neurogenic electric organ of the knife fish Sternarchus . J Cell Biol 53:210-224, 1972.Crossref 22. Rosenbluth J: Intramembranous particle distribution at the node of Ranvier and adjacent axolemma in myelinated axons of the frog brain . J Neurocytol 5:731-745, 1976.Crossref 23. Kristol C, Akert K, Sandri C, et al: The Ranvier nodes in the neurogenic electric organ of the knifefish Sternarchus: A freeze-etching study on the distribution of membrane-associated particles . Brain Res 125:197-212, 1977.Crossref 24. Ritchie JM, Rogart RB: The density of sodium channels in mammalian myelinated nerve fibers and the nature of the axonal membrane under the myelin sheath . Proc Natl Acad Sci USA 74:211-215, 1977.Crossref 25. Nonner W, Rojas E, Stämpfli R: Gating currents in the node of Ranvier: Voltage and time dependence . Philos Trans R Soc Lond (Biol) 270:483-492, 1975.Crossref 26. Ritchie JM, Rogart RB, Strichartz G: A new method for labeling saxitoxin and its binding to non-myelinated fibres of the rabbit vagus, lobster walking, and garfish olfactory nerves . J Physiol 261:477-494, 1976. 27. Bostock H, Sears TA: Continuous conduction in demyelinated mammalian nerve fibres . Nature 263:786-787, 1976.Crossref 28. Rasminsky M, Kearney RE: Continuous conduction in large diameter bare axons in spinal roots of dystrophic mice . Neurology 26:367, 1976. 29. MacKay RP, Hirano A: Forms of benign multiple sclerosis: Report of two clinically silent cases discovered at autopsy . Arch Neurol 17:588-600, 1967.Crossref 30. Namerow NS, Thompson LR: Plaques, symptoms, and the remitting course of multiple sclerosis . Neurology 19:765-774, 1969.Crossref 31. Ghatak NR, Hirano A, Lijtmaer H, et al: Asymptomatic demyelinated plaque in the spinal cord . Arch Neurol 30:484-486, 1974.Crossref 32. Wisniewski H, Oppenheimer D, McDonald WI: Relation between myelination and function in MS and EAE . J Neuropathol Exp Neurol 35:327, 1976.Crossref 33. Sidman RL, Green MC, Appel SH: Catalog of the Neurological Mutants of the Mouse . Cambridge, Harvard University Press, 1965. 34. Simons DJ: A note on the effect of heat and cold upon certain symptoms of multiple sclerosis . Bull Neurol Inst NY 6:385-386, 1937. 35. Guthrie TC: Visual and motor changes in patients with multiple sclerosis: A result of induced changes in environmental temperature . Arch Neurol Psychiatry 65:437-451, 1951.Crossref 36. Davis FA, Jacobson S: Altered thermal sensitivity in injured and demyelinated nerve . J Neurol Neurosurg Psychiatry 34:551-561, 1971.Crossref 37. Rasminsky M: The effects of temperature on conduction in demyelinated single nerve fibers . Arch Neurol 28:287-292, 1973.Crossref 38. Davis FA, Becker FO, Michael JA, et al: Effect of intravenous sodium bicarbonate, disodium edetate (Na2EDTA), and hyperventilation on visual and oculomotor signs in multiple sclerosis . J Neurol Neurosurg Psychiatry 33:723-732, 1970.Crossref 39. Becker FO, Michael JA, Davis FA: Acute effects of oral phosphate on visual function in multiple sclerosis . Neurology 24:601-607, 1974.Crossref 40. Harrison BM, McDonald WI, Ochoa J: Remyelination in the central diphtheria toxin lesion . J Neurol Sci 17:293-302, 1972.Crossref 41. Suzuki K, Andrews JM, Waltz JM, et al: Ultrastructural studies of multiple sclerosis . Lab Invest 20:444-454, 1969. 42. Gledhill RF, Harrison BM, McDonald WI: Pattern of remyelination in the CNS . Nature 244:443-444, 1973.Crossref 43. Brill MH, Waxman SG, Moore JW, et al: Conduction velocity and spike configuration in myelinated fibers: Computed dependence on internode distance . J Neurol Neurosurg Psychiatry , to be published.

Journal

Archives of Neurology – American Medical Association

Published: Oct 1, 1977

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