The effects of taipoxin and notexin on the function and fine structure of the murine neuromuscular junction.
The isolated neurotoxins taipoxin and notexin from the venoms of the Elapidae, Oxyuranus scutellatus and Notechis scutatus scutatus respectively cause a neuromuscular block when administered to the mouse in vivo or to the phrenic nerve-hemidiaphragm preparation in vitro. The block is preceded by a latency period during which the toxins bind irreversibly to the nerve. The period is shortened by nerve activity. The frequency of the miniature end-plate potentials is gradually reduced, almost to zero, and their amplitude distribution is altered; small and very large miniature endplate potentials appearing. Ultrastructurally the endplates are altered in the presynaptic portion but not in the postsynaptic part. In an early stage of poisoning the axolemma has an increased number of omega-shaped indentations similar in size to synaptic vesicles. At a later stage, when the animals die of respiratory paralysis, the axolemmal indentations are more numerous and the synaptic vesicles greatly reduced in number, the remaining vesicles having a variable and frequently larger than normal size. When impulse activity in the phrenic nerve is stopped by cutting the nerve before the administration of toxin there is no reduction in the number of synaptic vesicles, only the appearance of an increased number of axolemmal indentations. It is suggested that taipoxin and notexin irreversibly interfere with the formation of synaptic vesicles by arresting vesicle membrane recycling at the level of the axolemma. When the pre-existing store of vesicles is depleted, by nerve activity, a neuromuscular block results.
Cull-Candy
S G
SG
Dept. of Pharmacology, Lund University, Sweden.
Fohlman
J
J
Gustavsson
D
D
Lüllmann-Rauch
R
R
Thesleff
S
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D004546:Elapid Venoms / Q000633:toxicity*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008854:Microscopy, Electron; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D013570:Synaptic Membranes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D004546:Elapid Venoms; D009466:Neuromuscular Blocking Agents; C005082:notexin; C015523:taipoxin; D000109:Acetylcholine