Envenoming bites by kraits: the biological basis of treatment-resistant neuromuscular paralysis.
Beta-bungarotoxin, a neurotoxic phospholipase A2 is a major fraction of the venom of kraits. The toxin was inoculated into one hind limb of young adult rats. The inoculated hind limb was paralysed within 3 h, and remained paralysed for 2 days. The paralysis was associated with the loss of synaptic vesicles from motor nerve terminal boutons, a decline in immunoreactivity of synaptophysin, SNAP-25 and syntaxin, a loss of muscle mass and the upregulation of NaV(1.5) mRNA and protein. Between 3 and 6 h after the inoculation of toxin, some nerve terminal boutons exhibited clear signs of degeneration. Others appeared to be in the process of withdrawing from the synaptic cleft and some boutons were fully enwrapped in terminal Schwann cell processes. By 12 h all muscle fibres were denervated. Re-innervation began at 3 days with the appearance of regenerating nerve terminals, a return of neuromuscular function in some muscles and a progressive increase in the immunoreactivity of synaptophysin, SNAP-25 and syntaxin. Full recovery occurred at 7 days. The data were compared with recently published clinical data on envenoming bites by kraits and by extrapolation we suggest that the acute, reversible denervation caused by beta-bungarotoxin is a credible explanation for the clinically important, profound treatment-resistant neuromuscular paralysis seen in human subjects bitten by these animals.
Prasarnpun
S
S
School of Neurology, Neurobiology and Psychiatry, Faculty of Medical Sciences, University of Newcastle upon Tyne, UK.
Walsh
J
J
Awad
S S
SS
Harris
J B
JB
D000109:Acetylcholine / Q000032:analysis; D000818:Animals; D002038:Bungarotoxins / Q000506:poisoning*; D017838:Bungarus; D005260:Female; D006614:Hindlimb; D006801:Humans; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009469:Neuromuscular Junction / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D050765:Qa-SNARE Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012910:Snake Venoms / Q000506:poisoning*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D016708:Synaptophysin / Q000032:analysis; D050825:Synaptosomal-Associated Protein 25 / Q000032:analysis
D002038:Bungarotoxins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D050765:Qa-SNARE Proteins; D012333:RNA, Messenger; C568320:SCN5A protein, human; C568322:Scn5a protein, rat; D012910:Snake Venoms; D015222:Sodium Channels; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D000109:Acetylcholine