Stonustoxin: effects on neuromuscular function in vitro and in vivo.
Stonustoxin (8-50 micrograms/ml) produced a rapid and concentration-dependent rise in tension (contracture) of the electrically stimulated mouse hemidiaphragm followed by a gradual waning of tension from the peak to the baseline; the nerve-evoked and the directly (muscle)-evoked twitches of the hemidiaphragm were also progressively and irreversibly blocked in a time- and concentration-dependent manner. Stonustoxin (22 and 44 micrograms/ml) produced a similar rapid rise in tension of the chick biventer cervicis muscle as well as irreversible and concentration-dependent blockade of nerve-evoked twitches and contractures produced by acetylcholine (200 microM), carbachol (8 microM) and KCl (40 mM). The muscle contracture produced by stonustoxin was blocked by dantrolene sodium (6 microM) but not by tubocurarine (15 microM). Moreover, stonustoxin (40 micrograms/ml) did not inhibit nerve conduction in the toad sciatic nerve and stonustoxin (60 micrograms/ml) did not exhibit any anticholinesterase activity. The inhibition of neuromuscular function by stonustoxin in the mouse hemidiaphragm and chick biventer cervicis muscle can therefore be attributed to some irreversible myotoxic action(s) of the toxin, whereas the stonustoxin-induced muscle contractures could have been mediated via depolarization of muscle fibres.
Low
K S
KS
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Gwee
M C
MC
Yuen
R
R
Gopalakrishnakone
P
P
Khoo
H E
HE
D000818:Animals; D002025:Bufonidae; D002645:Chickens; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D005397:Fish Venoms / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology
D005397:Fish Venoms; D009466:Neuromuscular Blocking Agents; C073228:stonustoxin