A study onthemembranedepolarization ofskeletal muscles caused byascorpion toxin, seaanemone toxin IIandcrotamine andtheinteraction between toxins

1 Quinquestriatus toxin (QTX)isolated fromthevenomofascorpion (Leiurus quinquestriatus) andseaanemone(Anemonia sulcata) toxin IIenhanced thetwitch response oftheratandmouse diaphragms andlikecrotamine (isolated fromthevenomofCrotalus durissus terrificus) caused spontaneous fasciculation ofthemuscle. 2 Trains ofaction potentials inmuscles at70-250Hz, whichcouldnotbeantagonized by (+)-tubocurarine, weretriggered bysingle stimulation oroccurred spontaneously after treatment withthese toxins. 3 QTX andtoxin IIprolonged theratmuscle action potential 3to4foldwhereas crotamine prolonged theaction potential byonly30%. 4 Themembranepotential wasdepolarized fromabout-82mV to -55mV bycrotamine 2jigml -,-41mV bytoxin II5jig ml-andto-5OmVbyQTX1jigml-1. Theconcentrations to induce50%maximaldepolarization (Ko.5) were0.07, 0.15and>0.4)jgml-1, respectively, for QTX,crotamine andtoxinII,whereastheratesofdepolarization wereintheordertoxin II > crotamine > QTX.Thedepolarizing effects ofcrotamine andQTX,butnotoftoxinII,were saturable. 5 Thedepolarizing effects ofallthree toxins wereirreversible whereas themembranepotential could berestored bytetrodotoxin non-competitively. 6 Simultaneous treatment withcrotamine andQTXorcrotamine andtoxin IIatconcentrations belowK0.5 caused onlyadditive effects ondepolarization. 7 Whenthemuscle wasdepolarized bypretreating withasaturating concentration ofcrotamine, theonset ofdepolarization byQTX wasgreatly retarded whereas thatbytoxin IIwasunaffected. Action potentials werefurther prolonged inbothcases. 8 Itisinferred that all three peptide toxins actatsites onthesodium channel andthebinding sites forQTXandcrotamine overlap toaconsiderable extent. Ontheother hand, thesite fortoxin II appears nottooverlap withthat ofcrotamine butmayoverlap withthat ofQTX.