Interactions of a Cobra Neurotoxin and Affinity Labels of the Acetylcholine Receptor in the Electroplax

The principal neurotoxin of Naja naja siamensis alters interactions with the reduced acetylcholine receptor in the electroplax of one inactivating and two activating affinity reagents. Prior application of this cobra toxin to the dithiothreitol-treated electroplax prevents the depolarization otherwise resulting from the reaction with the activating affinity reagents and blocks the reaction with the receptor of the inactivating affinity reagent. Subsequent application of the toxin reverses the depolarization following the reaction of one of the activating affinity reagents only. It has been previously found that reversibly acting competitive inhibitors such as d -tubocurarine reverse the depolarization following the reaction of either of these activating reagents; the depolarization recurs when the competitive inhibitor is removed by washing. It is inferred that the neurotoxin and all three affinity reagents have overlapping although not identical sites or modes of attachment to the receptor. All bind to the negative subsite of the acetylcholine-binding site but also have other subsites of attachment. d -Tubocurarine binds either to a site with a common subsite or to a wholly distinct but strongly interacting site.