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. 1977 Feb;265(1):63–84. doi: 10.1113/jphysiol.1977.sp011705

The production of denervation-like changes in rat muscle by colchicine, without interference with axonal transport or muscle activity.

A Cangiano, J A Fried
PMCID: PMC1307808  PMID: 66309

Abstract

1. Rat extensor digitorum longus (EDL) muscles were examined after colchicine treatment of the sciatic nerve. Colchicine was applied in one of two ways: (i) a single sub-epineural injection; (ii) a chronically implanted silicone cuff. 2. After the sub-epineural injection, the entire membrane of muscle fibres became sensitive to iontophoretically applied acetylcholine and the muscle action potentials became resistant to tetrodotoxin. However, the majority of these fibres were found to be normally innervated. 3. These effects were not restricted to the EDL muscle of the colchicine injected side but were also found in the EDL muscle of the contralateral side, indicating that the action of colchicine was systemic. 4. In the treated sciatic nerve there was a partial block of axonal transport of 3H-labelled proteins, which correlated with a partial paralysis of the ipsilateral leg. However, axoplasmic transport was found to be normal in the contralateral sciatic nerve and the contralateral limb was not paralysed despite the supersensitivity of the investigated muscle on that side. 5. When colchicine was applied with a silicone cuff, denervation-like changes were confined to the ipsilateral EDL muscle. However, impulse conduction block at the level of the cuff was usually observed. 6. It is concluded that (i) colchicine can produce denervation-like changes in normally active muscle without blocking axoplasmic transport, through an action probably exerted directly on the muscle membrane, and (ii) that colchicine-cuff experiments failed to provide unambiguous evidence in support of the existence of neurotrophic influences on the muscle membrane.

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Selected References

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  1. ANGEVINE J. B., Jr Nerve destruction by colchicine in mice and golden hamsters. J Exp Zool. 1957 Nov;136(2):363–391. doi: 10.1002/jez.1401360209. [DOI] [PubMed] [Google Scholar]
  2. AXELSSON J., THESLEFF S. A study of supersensitivity in denervated mammalian skeletal muscle. J Physiol. 1959 Jun 23;147(1):178–193. doi: 10.1113/jphysiol.1959.sp006233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Albuquerque E. X., McIsaac R. J. Fast and slow mammalian muscles after denervation. Exp Neurol. 1970 Jan;26(1):183–202. doi: 10.1016/0014-4886(70)90099-3. [DOI] [PubMed] [Google Scholar]
  4. Albuquerque E. X., Schuh F. T., Kauffman F. C. Early membrane depolarization of the fast mammalian muscle after denervation. Pflugers Arch. 1971;328(1):36–50. doi: 10.1007/BF00587359. [DOI] [PubMed] [Google Scholar]
  5. Albuquerque E. X., Thesleff S. A comparative study of membrane properties of innervated and chronically denervated fast and slow skeletal muscles of the rat. Acta Physiol Scand. 1968 Aug;73(4):471–480. doi: 10.1111/j.1365-201x.1968.tb10886.x. [DOI] [PubMed] [Google Scholar]
  6. Albuquerque E. X., Warnick J. E., Tasse J. R., Sansone F. M. Effects of vinblastine and colchicine on neural regulation of the fast and slow skeletal muscles of the rat. Exp Neurol. 1972 Dec;37(3):607–634. doi: 10.1016/0014-4886(72)90103-3. [DOI] [PubMed] [Google Scholar]
  7. Cangiano A. Acetylcholine supersensitivity: the role of neurotrophic factors. Brain Res. 1973 Aug 17;58(1):255–259. doi: 10.1016/0006-8993(73)90842-1. [DOI] [PubMed] [Google Scholar]
  8. Cangiano A., Fried J. A. Proceedings: Neurotrophic control of skeletal muscle of the rat. J Physiol. 1974 May;239(1):31P–33P. [PubMed] [Google Scholar]
  9. Cohen S. A., Fischbach G. D. Regulation of muscle acetylcholine sensitivity by muscle activity in cell culture. Science. 1973 Jul 6;181(4094):76–78. doi: 10.1126/science.181.4094.76. [DOI] [PubMed] [Google Scholar]
  10. DEL CASTILLO J., KATZ B. On the localization of acetylcholine receptors. J Physiol. 1955 Apr 28;128(1):157–181. doi: 10.1113/jphysiol.1955.sp005297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dahlström A. Effect of colchicine on transport of amine storage granules in sympathetic nerves of rat. Eur J Pharmacol. 1968 Dec;5(1):111–113. doi: 10.1016/0014-2999(68)90165-9. [DOI] [PubMed] [Google Scholar]
  12. Drachman D. B. Trophic functions of the neuron. 3. Mechanisms of neurotrophic interactions. The role of acetylcholine as a neurotropic transmitter. Ann N Y Acad Sci. 1974 Mar 22;228(0):160–176. doi: 10.1111/j.1749-6632.1974.tb20508.x. [DOI] [PubMed] [Google Scholar]
  13. Drachman D. B., Witzke F. Trophic regulation of acetylcholine sensitivity of muscle: effect of electrical stimulation. Science. 1972 May 5;176(4034):514–516. doi: 10.1126/science.176.4034.514. [DOI] [PubMed] [Google Scholar]
  14. EMMELIN N., MALM L. DEVELOPMENT OF SUPERSENSITIVITY AS DEPENDENT ON THE LENGTH OF DEGENERATING NERVE FIBRES. Q J Exp Physiol Cogn Med Sci. 1965 Apr;50:142–145. doi: 10.1113/expphysiol.1965.sp001776. [DOI] [PubMed] [Google Scholar]
  15. FERGUSON F. C., Jr Colchicine. I. General pharmacology. J Pharmacol Exp Ther. 1952 Nov;106(3):261–270. [PubMed] [Google Scholar]
  16. Fernandez H. L., Ramirez B. U. Muscle fibrillation induced by blockage of axoplasmic transport in motor nerves. Brain Res. 1974 Oct 25;79(3):385–395. doi: 10.1016/0006-8993(74)90436-3. [DOI] [PubMed] [Google Scholar]
  17. Fowler T. J., Danta G., Gilliatt R. W. Recovery of nerve conduction after a pneumatic tourniquet: observations on the hind-limb of the baboon. J Neurol Neurosurg Psychiatry. 1972 Oct;35(5):638–647. doi: 10.1136/jnnp.35.5.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harris J. B., Thesleff S. Nerve stump length and membrane changes in denervated skeletal muscle. Nat New Biol. 1972 Mar 15;236(63):60–61. doi: 10.1038/newbio236060a0. [DOI] [PubMed] [Google Scholar]
  19. Hofmann W. W., Thesleff S. Studies on the trophic influence of nerve on skeletal muscle. Eur J Pharmacol. 1972 Dec;20(3):256–260. doi: 10.1016/0014-2999(72)90182-3. [DOI] [PubMed] [Google Scholar]
  20. Jones R., Vrbová G. Effect of muscle activity on denervation hypersensitivity. J Physiol. 1970 Sep;210(2):144P–145P. [PubMed] [Google Scholar]
  21. Kauffman F. C., Warnick J. E., Albuquerque E. X. Uptake of [3H]colchicine from silastic implants by mammalian nerves and muscles. Exp Neurol. 1974 Sep;44(3):404–416. doi: 10.1016/0014-4886(74)90204-0. [DOI] [PubMed] [Google Scholar]
  22. Kreutzberg G. W. Neuronal dynamics and axonal flow. IV. Blockage of intra-axonal enzyme transport by colchicine. Proc Natl Acad Sci U S A. 1969 Mar;62(3):722–728. doi: 10.1073/pnas.62.3.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Locke S., Solomon H. C. Relation of resting potential of rat gastrocnemius and soleus muscles to innervation, activity, and the Na-K pump. J Exp Zool. 1967 Dec;166(3):377–386. doi: 10.1002/jez.1401660310. [DOI] [PubMed] [Google Scholar]
  24. Lomo T., Rosenthal J. Control of ACh sensitivity by muscle activity in the rat. J Physiol. 1972 Mar;221(2):493–513. doi: 10.1113/jphysiol.1972.sp009764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lomo T., Westgaard R. H. Further studies on the control of ACh sensitivity by muscle activity in the rat. J Physiol. 1975 Nov;252(3):603–626. doi: 10.1113/jphysiol.1975.sp011161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miledi R., Zelená J. Sensitivity to acetylcholine in rat slow muscle. Nature. 1966 May 21;210(5038):855–856. doi: 10.1038/210855a0. [DOI] [PubMed] [Google Scholar]
  27. OCHS S., BURGER E. Movement of substance proximo-distally in nerve axons as studied with spinal cord injections of radioactive phosphorus. Am J Physiol. 1958 Sep;194(3):499–506. doi: 10.1152/ajplegacy.1958.194.3.499. [DOI] [PubMed] [Google Scholar]
  28. Ochs S. Rate of fast axoplasmic transport in mammalian nerve fibres. J Physiol. 1972 Dec;227(3):627–645. doi: 10.1113/jphysiol.1972.sp010051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Periśić M., Cuénod M. Synaptic transmission depressed by colchicine blockade of axoplasmic flow. Science. 1972 Mar 10;175(4026):1140–1142. doi: 10.1126/science.175.4026.1140. [DOI] [PubMed] [Google Scholar]
  30. Purves D., Sakmann B. Membrane properties underlying spontaneous activity of denervated muscle fibres. J Physiol. 1974 May;239(1):125–153. doi: 10.1113/jphysiol.1974.sp010559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Purves D., Sakmann B. The effect of contractile activity on fibrillation and extrajunctional acetylcholine-sensitivity in rat muscle maintained in organ culture. J Physiol. 1974 Feb;237(1):157–182. doi: 10.1113/jphysiol.1974.sp010475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Redfern P., Thesleff S. Action potential generation in denervated rat skeletal muscle. I. Quantitative aspects. Acta Physiol Scand. 1971 Apr;81(4):557–564. doi: 10.1111/j.1748-1716.1971.tb04932.x. [DOI] [PubMed] [Google Scholar]
  33. Robert E. D., Oester Y. T. Absence of supersensitivity to acetylcholine in innervated muscle subjected to a prolonged pharmacologic nerve block. J Pharmacol Exp Ther. 1970 Jul;174(1):133–140. [PubMed] [Google Scholar]
  34. Singer M., Steinberg M. C. Wallerian degeneration: a reevaluation based on transected and colchicine-poisoned nerves in the Amphibian, Triturus. Am J Anat. 1972 Jan;133(1):51–83. doi: 10.1002/aja.1001330105. [DOI] [PubMed] [Google Scholar]
  35. THESLEFF S. Supersensitivity of skeletal muscle produced by botulinum toxin. J Physiol. 1960 Jun;151:598–607. doi: 10.1113/jphysiol.1960.sp006463. [DOI] [PMC free article] [PubMed] [Google Scholar]

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