Premium
EFFECT OF CROTAMINE, A TOXIN OF SOUTH AMERICAN RATTLESNAKE VENOM, ON THE SODIUM CHANNEL OF MURINE SKELETAL MUSCLE
Author(s) -
CHANG C. CHIUNG,
TSENG K. HONG
Publication year - 1978
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.1476-5381.1978.tb07811.x
Subject(s) - depolarization , tetrodotoxin , ouabain , chemistry , membrane potential , biophysics , procaine , medicine , endocrinology , sodium , anesthesia , anatomy , biology , biochemistry , organic chemistry
1 Crotamine (0.5 μg/ml) augmented the single twitch response of the rat and mouse isolated diaphragm to direct stimulation and prolonged the time course of contraction. At higher doses (10 to 50 μg/ml), contracture was observed with spontaneous fibrillation. 2 The resting membrane potential of diaphragm was rapidly depolarized to about −50 mV within 5 minutes. No increase of depolarization occurred on prolongation of the incubation time or increase of crotamine concentration from 0.5 μg/ml to 50 μg/ml. The effect was not reversed by washing. 3 Tetrodotoxin, low Na + (12 m m ), Ca 2+ (10 m m ) and procaine (1 m m ) prevented the crotamine‐depolarization. However, depolarization resumed when crotamine and the antagonists were removed. 4 Low Cl− (8.5 m m ) and pretreatment with ouabain enhanced depolarization by crotamine. 5 High K + (25 to 50 m m ) prevented the further depolarization by crotamine and the membrane potential was restored to normal on washout of crotamine with normal Tyrode solution. 6 Effective membrane resistance was decreased by about 50% by crotamine. 7 24 Na‐influx of the rat diaphragm was increased by crotamine. 42 K‐influx was slightly increased if tetrodotoxin was also present but was decreased in the absence of tetrodotoxin. 8 No effect on the miniature and evoked endplate potential of the rat diaphragm was observed. Skeletal muscles from frog and chick were not affected. 9 It is inferred that crotamine acts on a molecule regulating the Na + ‐ permeability of the Na + channel of murine muscles. It is proposed that extracellular K + depresses the permeability of the Na + channel by acting on the same regulator molecule.