Demonstration of increased permeability as a factor in the effect of acetylcholine on the electrical activty of venom-treated axons.

D-Tubocurarine (curare) and acetylcholine (ACh) had been found to block electrical activity after treatment of squid giant axons with cottonmouth moccasin venom at a concentration which had no effect on conduction. It has now been demonstrated that this effect is attributable to reduction of permeability barriers. The penetration of externally applied C(14)-labeled dimethylcurare, ACh, choline, and trimethylamine into the axoplasm of the squid giant axon was determined in axons treated with either cottonmouth, rattlesnake, or bee venom, and in untreated control axons. The lipid-soluble tertiary nitrogen compound trimethylamine readily penetrated into the axoplasm of untreated axons. In contrast, after exposure of the axons to the lipid-insoluble quaternary nitrogen compounds for 1 hour their presence in the axoplasm was hardly detectable (less than 1 per cent). However, following 15microg/ml cottonmouth venom 1 to 5 per cent of their external concentration is found within the axoplasm while following 50microg/ml venom 10 to 50 per cent enters. The penetration of dimethylcurare is also increased by 10 microg/ml bee venom but not by 1 microg/ml bee venom nor 1000 microg/ml rattlesnake venom. The experiments show that when ACh and curare, following venom treatment, affect electrical activity, they also penetrate into the axon. Treatments which do not increase penetration are also ineffective in rendering the compounds active.