Mode of neuromuscular blocking action of ceruleotoxin

Ceruleotoxin is an acidic toxin protein from a Bungarus venom which has recently been clarified as B. fasciatus venom. The toxin at a low concentration (10(-6) g/ml) abolished the twitch response of the indirectly stimulated biventer cervicis muscle of the chick, without affecting the response of acetylcholine or carbamylcholine. At a higher concentration (10(-5) g/ml), the toxin, in addition to inhibition of the twitch response, caused contracture in the chick biventer cervicis muscle and reduced the response to acetylcholine or carbamylcholine in both the innervated chick cervical and denervated rat diaphragm muscles. Electrophysiological studies on the rat phrenic nerve--diaphragm preparation showed that ceruleotoxin at a low concentration caused an initial inhibition followed by recovery of the quantal content of endplate potentials and then a second phase of inhibition leading to complete failure. At a higher concentration, the toxin gradually reduced the resting membrane potential of the diaphragm muscle to a level lower than 50 mV within 2 hr. In addition, enzyme assay showed that the toxin possessed phospholipase A activity comparable to that of other basic phospholipases A2 of snake venom origin. It is concluded that ceruleotoxin is a phospholipase A2 with presynaptic and myotropic actions on vertebrate nerve--muscle system similar to those of notexin from Notechis scutatus scutatus venom.