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. 1971 Sep;217(2):497–515. doi: 10.1113/jphysiol.1971.sp009582

The effect of type D botulinum toxin on frog neuromuscular junctions

A J Harris, R Miledi
PMCID: PMC1331788  PMID: 4329008

Abstract

1. Botulinum toxin type D blocks neuromuscular transmission in frogs. Motor nerve impulses continue to invade the nerve terminals but cease to evoke the phasic release of transmitter normally associated with them.

2. Sensory receptors in the muscle continue to generate impulses even after 4 days of continuous exposure to botulinum toxin.

3. Contrary to expectations, spontaneous miniature end-plate potentials did not disappear completely after botulinum intoxication; they still occurred, although with reduced frequency, in most end-plates. These miniature potentials had a skew amplitude distribution instead of the bell-shaped distribution of normal end-plates.

4. The electron-microscopic appearance of botulinum-poisoned end-plates was not obviously altered.

5. Even though after botulinum nerve impulses fail to release transmitter, tetanic nerve stimulation causes an increase in the frequency of miniature end-plate potentials. Many of the unit potentials which appear during the tetanic period are of an amplitude which is larger than that of spontaneous potentials, indicating that a different class of unit is being released preferentially. Some implications of this finding are briefly discussed.

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Selected References

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

  1. AMBACHE N., LESSIN A. W. Classification of intestinomotor drugs by means of type D botulinum toxin. J Physiol. 1955 Mar 28;127(3):449–478. doi: 10.1113/jphysiol.1955.sp005270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ambache N. The peripheral action of Cl. botulinum toxin. J Physiol. 1949 Mar 15;108(2):127–141. [PMC free article] [PubMed] [Google Scholar]
  3. BIRKS R., KATZ B., MILEDI R. Physiological and structural changes at the amphibian myoneural junction, in the course of nerve degeneration. J Physiol. 1960 Jan;150:145–168. doi: 10.1113/jphysiol.1960.sp006379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BROOKS V. B. An intracellular study of the action of repetitive nerve volleys and of botulinum toxin on miniature end-plate potentials. J Physiol. 1956 Nov 28;134(2):264–277. doi: 10.1113/jphysiol.1956.sp005642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BROOKS V. B. The action of botulinum toxin on motor-nerve filaments. J Physiol. 1954 Mar 29;123(3):501–515. doi: 10.1113/jphysiol.1954.sp005067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BURGEN A. S. V., DICKENS F., ZATMAN L. J. The action of botulinum toxin on the neuro-muscular junction. J Physiol. 1949 Aug;109(1-2):10–24. doi: 10.1113/jphysiol.1949.sp004364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carpenter F. G. Motor responses of the urinary bladder and skeletal muscle in botulinum intoxicated rats. J Physiol. 1967 Jan;188(1):1–11. doi: 10.1113/jphysiol.1967.sp008119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harris A. J., Miledi R. Prolonged survival of isolated frog muscle and its sensitivity to acetylcholine. Nature. 1966 Feb 12;209(5024):716–717. doi: 10.1038/209716a0. [DOI] [PubMed] [Google Scholar]
  9. KATZ B., MILEDI R. PROPAGATION OF ELECTRIC ACTIVITY IN MOTOR NERVE TERMINALS. Proc R Soc Lond B Biol Sci. 1965 Feb 16;161:453–482. doi: 10.1098/rspb.1965.0015. [DOI] [PubMed] [Google Scholar]
  10. KATZ B., MILEDI R. THE MEASUREMENT OF SYNAPTIC DELAY, AND THE TIME COURSE OF ACETYLCHOLINE RELEASE AT THE NEUROMUSCULAR JUNCTION. Proc R Soc Lond B Biol Sci. 1965 Feb 16;161:483–495. doi: 10.1098/rspb.1965.0016. [DOI] [PubMed] [Google Scholar]
  11. KRNJEVIC K., MILEDI R. Failure of neuromuscular propagation in rats. J Physiol. 1958 Mar 11;140(3):440–461. [PMC free article] [PubMed] [Google Scholar]
  12. Katz B., Miledi R. Modification of transmitter release by electrical interference with motor nerve endings. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):1–7. doi: 10.1098/rspb.1967.0008. [DOI] [PubMed] [Google Scholar]
  13. Katz B., Miledi R. The effect of local blockage of motor nerve terminals. J Physiol. 1968 Dec;199(3):729–741. doi: 10.1113/jphysiol.1968.sp008675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Katz B., Miledi R. The release of acetylcholine from nerve endings by graded electric pulses. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):23–38. doi: 10.1098/rspb.1967.0011. [DOI] [PubMed] [Google Scholar]
  15. MILEDI R. Properties of regenerating neuromuscular synapses in the frog. J Physiol. 1960 Nov;154:190–205. doi: 10.1113/jphysiol.1960.sp006573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miledi R., Slater C. R. Electrophysiology and electron-microscopy of rat neuromuscular junctions after nerve degeneration. Proc R Soc Lond B Biol Sci. 1968 Feb 27;169(1016):289–306. doi: 10.1098/rspb.1968.0012. [DOI] [PubMed] [Google Scholar]
  17. Miledi R., Slater C. R. On the degeneration of rat neuromuscular junctions after nerve section. J Physiol. 1970 Apr;207(2):507–528. doi: 10.1113/jphysiol.1970.sp009076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miledi R., Stefani E. Miniature potentials in denervated slow muscle fibres of the frog. J Physiol. 1970 Jul;209(1):179–186. doi: 10.1113/jphysiol.1970.sp009161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miledi R., Thies R. Tetanic and post-tetanic rise in frequency of miniature end-plate potentials in low-calcium solutions. J Physiol. 1971 Jan;212(1):245–257. doi: 10.1113/jphysiol.1971.sp009320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. STOVER J. H., Jr, FINGERMAN M., FORESTER R. H. Botulinum toxin and the motor end plate. Proc Soc Exp Biol Med. 1953 Oct;84(1):146–147. doi: 10.3181/00379727-84-20570. [DOI] [PubMed] [Google Scholar]
  21. Simpson L. L., Tapp J. T. Actions of calcium and magnesium on the rate of onset of botulinum toxin paralysis of the rat diaphragm. Int J Neuropharmacol. 1967 Nov;6(6):485–492. doi: 10.1016/0028-3908(67)90048-2. [DOI] [PubMed] [Google Scholar]
  22. 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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