Neurotoxicity of ammodytoxin a in the envenoming bites of Vipera ammodytes ammodytes.
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.
Logonder
Uros
U
Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia.
Krizaj
Igor
I
Rowan
Edward G
EG
Harris
John B
JB
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003964:Diaphragm / Q000473:pathology; D004594:Electrophysiology; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D010791:Phrenic Nerve / Q000473:pathology; D012909:Snake Bites / Q000473:pathology*; D014757:Viper Venoms / Q000633:toxicity*
D009498:Neurotoxins; D014757:Viper Venoms; C068117:ammodytoxin A