Neurotoxicity of ammodytoxin A in the envenoming bites of vipera ammodytes ammodytes

U. Logonder, I. Krizaj, E.G. Rowan, J.B. Harris

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Envenoming bites by Vipera ammodytes ammodytes (the long-nosed viper) can cause life-threatening neurotoxicity, particularly in children. We investigated the mechanisms of the neurotoxicity of ammodytoxin A, the principal toxin in the venom of these snakes, in isolated nerve-muscle preparations from mice. The toxin was bound selectively to the neuromuscular junction, and at concentrations similar to those likely to be found in the circulation of young bite victims, it blocked the response of the muscle to indirect but not direct stimulation. Electron microscopy showed that the toxin induced a small but insignificant depletion of synaptic vesicles from motor nerve terminals; nerve terminal mitochondria were swollen and damaged, but plasma membranes of terminal boutons were undamaged. Exposure to the toxin did not affect postjunctional acetylcholine receptors or cause structural damage to preterminal motor axons or muscle fibers. Spontaneous transmitter release was similarly unaffected. Taken together, these results indicate that ammodytoxin A is the principal agent involved in the neurotoxic activity of the venom of V ammodytes ammodytes and that the underlying cause of the failure of transmission may be the deenergization of the nerve terminal resulting from mitochondrial degeneration and subsequent impairment of coupling between the action-potential-induced depolarization of the nerve terminal and the evoked transmitter release. (C) 2008 American Association of Neuropathologists, Inc
LanguageEnglish
Pages1011-1019
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume67
Issue number10
DOIs
Publication statusPublished - Oct 2008

Fingerprint

Neuromuscular Junction
Bites and Stings
Muscles
Snake Venoms
Synaptic Vesicles
Venoms
Cholinergic Receptors
Action Potentials
Axons
Electron Microscopy
Mitochondria
Cell Membrane
ammodytoxin A

Keywords

  • ammodytoxin A
  • motor nerve terminals
  • neuromuscular junction
  • neurotoxicity
  • Vipera ammodytes ammodytes

Cite this

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title = "Neurotoxicity of ammodytoxin A in the envenoming bites of vipera ammodytes ammodytes",
abstract = "Envenoming bites by Vipera ammodytes ammodytes (the long-nosed viper) can cause life-threatening neurotoxicity, particularly in children. We investigated the mechanisms of the neurotoxicity of ammodytoxin A, the principal toxin in the venom of these snakes, in isolated nerve-muscle preparations from mice. The toxin was bound selectively to the neuromuscular junction, and at concentrations similar to those likely to be found in the circulation of young bite victims, it blocked the response of the muscle to indirect but not direct stimulation. Electron microscopy showed that the toxin induced a small but insignificant depletion of synaptic vesicles from motor nerve terminals; nerve terminal mitochondria were swollen and damaged, but plasma membranes of terminal boutons were undamaged. Exposure to the toxin did not affect postjunctional acetylcholine receptors or cause structural damage to preterminal motor axons or muscle fibers. Spontaneous transmitter release was similarly unaffected. Taken together, these results indicate that ammodytoxin A is the principal agent involved in the neurotoxic activity of the venom of V ammodytes ammodytes and that the underlying cause of the failure of transmission may be the deenergization of the nerve terminal resulting from mitochondrial degeneration and subsequent impairment of coupling between the action-potential-induced depolarization of the nerve terminal and the evoked transmitter release. (C) 2008 American Association of Neuropathologists, Inc",
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Neurotoxicity of ammodytoxin A in the envenoming bites of vipera ammodytes ammodytes. / Logonder, U.; Krizaj, I.; Rowan, E.G.; Harris, J.B.

In: Journal of Neuropathology and Experimental Neurology, Vol. 67, No. 10, 10.2008, p. 1011-1019.

Research output: Contribution to journalArticle

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AB - Envenoming bites by Vipera ammodytes ammodytes (the long-nosed viper) can cause life-threatening neurotoxicity, particularly in children. We investigated the mechanisms of the neurotoxicity of ammodytoxin A, the principal toxin in the venom of these snakes, in isolated nerve-muscle preparations from mice. The toxin was bound selectively to the neuromuscular junction, and at concentrations similar to those likely to be found in the circulation of young bite victims, it blocked the response of the muscle to indirect but not direct stimulation. Electron microscopy showed that the toxin induced a small but insignificant depletion of synaptic vesicles from motor nerve terminals; nerve terminal mitochondria were swollen and damaged, but plasma membranes of terminal boutons were undamaged. Exposure to the toxin did not affect postjunctional acetylcholine receptors or cause structural damage to preterminal motor axons or muscle fibers. Spontaneous transmitter release was similarly unaffected. Taken together, these results indicate that ammodytoxin A is the principal agent involved in the neurotoxic activity of the venom of V ammodytes ammodytes and that the underlying cause of the failure of transmission may be the deenergization of the nerve terminal resulting from mitochondrial degeneration and subsequent impairment of coupling between the action-potential-induced depolarization of the nerve terminal and the evoked transmitter release. (C) 2008 American Association of Neuropathologists, Inc

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