Binding of scorpion toxin to receptor sites associated with voltage-sensitive sodium channels in synaptic nerve ending particles.

Scorpion mono[‘2sIJiodotoxin binds to a single class of receptor sites associated with voltage-sensitive sodium channels in synaptic nerve ending particles (synaptosomes) with a KD of approximately 3 11~. Scorpion toxin binding is inhibited by depolarization of the synaptosomes with K+ or gramicidin or by lysis of the synaptosomes. Scorpion toxin binding is enhanced by batrachotoxin, veratridine, and aconitine if depolarization of the synaptosomes by these toxins is prevented by sodium-free medium containing 1 p tetrodotoxin. Batrachotoxin, veratridine, and aconitine act at a common receptor site in enhancing scorpion toxin binding. Batrachotoxin may be a full agonist at this receptor site, whereas veratridine and aconitine are partial agonists. The enhancement of scorpion toxin binding by batrachotoxin is accompanied by a large shift in the voltage dependence of scorpion toxin binding. These observations demonstrate allosteric interactions between the receptor sites for scorpion toxin and the alkaloid toxins. The results are considered in terms of a two-state allosteric model. In the presence of batrachotoxin, scorpion toxin binds to a single class of sites with a & of 1.6 no and a binding capacity of 1750 fmol/mg of protein. The voltage-sensitivity of these sites suggests that they are all associated with synaptosomes. Therefore, synaptosomes contain 63 scorpion toxin sites/individual nerve ending or 36 sites/pm’ of surface membrane. This density of sodium channels is similar to that observed in unmyelinated nerves.