Acute in vivo exposure to ethylcholine aziridinium (AF64A) depresses the secretion of quanta from motor nerve terminals.

Quantal release of acetylcholine was evaluated for soleus nerve-muscle preparations removed from mice treated with the cholinergic neurotoxin AF64A. Treatment with two and three times the LD50 (i.p.) of AF64A caused a marked reduction of the frequency of miniature end-plate potentials (mepps) and the amplitude of end-plate potentials (epps). Since the amplitude of mepps was not altered, the reduction of epps was not due to reduction in the number of molecules of acetylcholine (ACh) per quantum or the end-plate sensitivity to ACh, but to a reduction of the number of quanta released in response to a nerve action potential. While this effect was not reversed when preparations were washed for 3 h, exposure to the potassium channel blocker, 3,4-diaminopyridine returned the mean quantal content of epps to normal. These data further support a presynaptic site of action for AF64A, and suggest that it may acutely disrupt the ionic processes underlying transmitter release.