STONUSTOXIN - EFFECTS ON NEUROMUSCULAR FUNCTION IN-VITRO AND IN-VIVO

Stonustoxin (8-50 mu g/ml) produced a rapid and concentration-dependen t rise in tension (contracture) of the electrically stimulated mouse h emidiaphragm followed by a gradual waning of tension from the peak to the baseline; the nerve-evoked and the directly (muscle)-evoked twitch es of the hemidiaphragm were also progressively and irreversibly block ed in a time- and concentration-dependent manner. Stonustoxin (22 and 44 mu g/ml) produced a similar rapid rise in tension of the chick bive nter cervicis muscle as well as irreversible and concentration-depende nt blockade of nerve-evoked twitches and contractures produced by acet ylcholine (200 mu M), carbachol (8 mu M) and KCl (40 mM). The muscle c ontracture produced by stonustoxin was blocked by dantrolene sodium (6 mu M) but not by tubocurarine (15 mu M). Moreover, stonustoxin (40 mu g/ml) did not inhibit nerve conduction in the toad sciatic nerve and stonustoxin (60 mu g/ml) did not exhibit any anticholinesterase activi ty. The inhibition of neuromuscular function by stonustoxin in the mou se hemidiaphragm and chick biventer cervicis muscle can therefore be a ttributed to some irreversible myotoxic action(s) of the toxin, wherea s the stonustoxin-induced muscle contractures could have been mediated via depolarization of muscle fibres.