Dissociation of the crotoxin complex promoted by acetylcholine

Neuromuscular blockage at the presynaptic level is the main biological effect exerted by crotoxin, the major toxin from Crotalus durissus terrificus venom. This effect requires the dissociation of this complex at the target membrane in spite of its tightness and stability under physiological conditions of pH, ionic composition and temperature. Complex dissociation should be determined by a specific set of physicochemical conditions prevailing at the neuromuscular junction. In this regard, we have studied the effect of acetylcholine on the stability of the crotoxin complex, since this effector is present at relatively high concentrations near the presynaptic membrane of the neuromuscular junction. Evidences arising from spectrofluorometric measurements, changes in enzymatic activity and crotoxin B inactivation by b-bromophenacyl bromide indicate that acetylcholine is indeed able to promote complex dissociation at neutral pH values, apparently by titration of 2-3 carboxylate groups in crotoxin A. This effect may, at least in part, contribute in determining the target specificity of this toxin.