Premium
A study on the membrane depolarization of skeletal muscles caused by a scorpion toxin, sea anemone toxin II and crotamine and the interaction between toxins
Author(s) -
Chang C.C.,
Hong S.J.,
Su M.J.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb10004.x
Subject(s) - depolarization , toxin , venom , tetrodotoxin , marine toxin , neurotoxin , membrane potential , biology , scorpion toxin , chemistry , pharmacology , biophysics , biochemistry , scorpion
1 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. 2 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. 3 QTX and toxin II prolonged the rat muscle action potential 3 to 4 fold whereas crotamine prolonged the action potential by only 30%. 4 The membrane potential was depolarized from about −82 mV to −55 mV by crotamine 2 μg ml −1 , −41 mV by toxin II 5 μg ml −1 and to −50 mV by QTX 1 μg ml −1 . The concentrations to induce 50% maximal depolarization (K 0.5 ) were 0.07, 0.15 and > 0.4 μg ml −1 , respectively, for QTX, crotamine and toxin II, whereas the rates of depolarization were in the order toxin II > crotamine > QTX. The depolarizing effects of crotamine and QTX, but not of toxin II, were saturable. 5 The depolarizing effects of all three toxins were irreversible whereas the membrane potential could be restored by tetrodotoxin non‐competitively. 6 Simultaneous treatment with crotamine and QTX or crotamine and toxin II at concentrations below K 0.5 caused only additive effects on depolarization. 7 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.