Quinquestriatus toxin (QTX) isolated from the
venom of a scorpion (Leiurus quinquestriatus) and sea anemone (
Anemonia sulcata) toxin II enhanced the twitch response of the rat and mouse diaphragms and like
crotamine (isolated from the
venom of Crotalus durissus terrificus) caused spontaneous
fasciculation of the muscle. Trains of action potentials in muscles at 70-250 Hz, which could not be antagonized by (+)-
tubocurarine, were triggered by single stimulation or occurred spontaneously
after treatment with these toxins. QTX and toxin II prolonged the rat muscle action potential 3 to 4 fold whereas
crotamine prolonged the action potential by only 30%. The membrane potential was depolarized from about -82 mV to -55 mV by
crotamine 2 micrograms ml-1, -41 mV by toxin II 5 micrograms ml-1 and to -50 mV by QTX 1 microgram ml-1. The concentrations to induce 50% maximal depolarization (K0.5) were 0.07, 0.15 and greater than 0.4 microgram ml-1, respectively, for QTX,
crotamine and toxin II, whereas the rates of depolarization were in the order toxin II greater than or equal to
crotamine greater than QTX. The depolarizing effects of
crotamine and QTX, but not of toxin II, were saturable. The depolarizing effects of all three toxins were irreversible whereas the membrane potential could be restored by
tetrodotoxin non-competitively. Simultaneous treatment with
crotamine and QTX or
crotamine and toxin II at concentrations below K0.5 caused only additive effects on depolarization. When the muscle was depolarized by pretreating with a saturating concentration of
crotamine, the onset of depolarization by QTX was greatly retarded whereas that by toxin II was unaffected. Action potentials were further prolonged in both cases. 8 It is inferred that all three
peptide toxins act at sites on the
sodium channel and the binding sites for QTX and
crotamine overlap to a considerable extent. On the other hand, the site for toxin II appears not to overlap with that of
crotamine but may overlap with that of QTX.