Binding of scorpion neurotoxins to chick embryonic heart cells in culture and relationship to calcium uptake and membrane potential

Abstract

Stimulation of 45Ca uptake by scorpion neurotoxins in cultured chick embryonic heart cells has been shown to be directly linked to their effect on sodium channels. This property was used to compare the activity of 15 neurotoxins from five different species to their lethal effect in the mouse and immunological properties. As scorpion neurotoxins, the alkaloid neurotoxin veratridine enhanced 45Ca uptake, and an apparent positive cooperativity between the two drugs was observed. 125I-Labeled toxin II from the scorpion Androctonus australis Hector was shown to bind to chick heart cells specifically, saturably, and reversibly with high affinity (KD = 1--3 nM in sodium-free medium) and low capacity (10--20 fmol/mg cell protein). As shown by 45Ca uptake and radioactive toxin binding experiments, the affinity of scorpion neurotoxin to heart cell receptors was dependent on external K+ concentration. Toxin binding was lowered by increasing Na+ concentration in the medium and was abolished by veratridine in a sodium (140 mM) containing medium. As previously reported for neuroblastoma cells, all these results are in agreement with the membrane potential dependence of scorpion neurotoxin affinity for its membrane receptor.