Different effects of types A and B botulinum toxin on transmitter release at the rat neuromuscular junction

Blockade of neuromuscular transmission was produced in the lower hind limb of the rat by local injection of either crystalline type A botulinum toxin or purified type B botulinum neurotoxin. At 1, 3, 5 and 7 days after injection, the extensor digitorum longus nerve‐muscle preparation was excised and analyzed in vitro for alterations in spontaneous and nerve stimulus‐evoked quantal transmitter release. Muscles receiving type A toxin were paralyzed up to and including 7 days after injection. Muscles treated with type B toxin, although completely paralyzed at 1 and 3 days, twitched in response to nerve stimulation at 5 and 7 days after injection. Both toxins induced a marked decrease in the frequency of miniature endplate potentials but type A did so to a greater extent. The remaining population of miniature endplate potentials contained a greater frequency of potentials with small or large amplitudes and prolonged rise times compared to normal muscle. These changes were more pronounced with type A toxin than with type B toxin. In the presence of α‐dinitrophenol (1 mM), high frequency, fast‐rising miniature endplate potentials of uniform size reappeared. High K + (20 mM) was less effective in this respect. At 3 days after toxin injection nerve impulse evoked transmitter release was reduced more for type A treated muscles than for type B. However, 3,4‐diaminopyridine, an agent which increases nerve‐evoked transmitter release by increasing Ca 2+ influx, was more effective in reversing the paralysis in type A than in type B‐treated muscles. In contrast to type A, 3,4‐diaminopyridine induced in type B‐paralyzed muscle asynchronous endplate potentials in response to nerve stimuli and a posttetanic increase in miniature endplate potential frequency. The results show that type B toxin differs from type A, mainly by a shorter duration of action and by being less effectively antagonized by 3,4‐diaminopyridine. These findings have implications for the medical treatment of the two types of botulism