Chronic effects of botulinum toxin on neuromuscular transmission and sensitivity to acetylcholine in slow and fast skeletal muscle of the mouse.

1. A sublethal dose of botulinum toxin (type A) was injected into the muscles of one hind limb of the mouse causing local paralysis.2. Neuromuscular transmission and muscle sensitivity to acetylcholine (ACh) were studied in vitro in soleus and extensor digitorium longus (EDL) from 6 hr to 4 months after the injection of toxin.3. Both soleus and EDL failed to respond to nerve stimulation within 6 hr of the injection of toxin.4. In muscle fibres in which neuromuscular transmission was blocked, subthreshold end-plate potentials (e.p.p.s) were recorded. The amplitude of the e.p.p.s increased during recovery from the effects of the toxin and both muscles contracted in response to nerve stimulation after 2-3 weeks.5. For about 2 months muscles fatigued more rapidly than normal during repetitive nerve stimulation because of the low quantal content of e.p.p.s.6. Supersensitivity to ACh developed in 3-5 days and persisted after the return of neuromuscular transmission. Muscle sensitivity to ACh became normal when the rate of fatigue during nerve stimulation was normal.