The effects of tetanus toxin on neuromuscular transmission and on the morphology of motor end-plates in slow and fast skeletal muscle of the mouse.

Abstract

1. A sublethal dose of tetanus toxin was injected into the muscles of one hind leg of the mouse and caused local tetanus which persisted for 4 weeks.2. Neuromuscular transmission was studied in vitro in nerve-muscle preparations of soleus, a slow muscle, and extensor digitorum longus (EDL), a fast muscle, from 1 day to 6 months after the injection of toxin.3. Soleus failed to respond to nerve stimulation, became supersensitive to acetylcholine and showed spontaneous fibrillations for several weeks before returning to normal. EDL did not show these changes. A higher dose of tetanus toxin, lethal within 24 hr, caused paralysis of EDL as well as soleus.4. In muscle fibres in which neuromuscular transmission was blocked spontaneous miniature end-plate potentials (m.e.p.p.s) were recorded. The frequency of m.e.p.p.s was increased by repetitive nerve stimulation but not by raising the external potassium concentration.5. The amplitude of spontaneous m.e.p.p.s showed a skew distribution because of a disproportionate number of potentials of less than 0.2 mV.6. Raising the external calcium concentration did not restore neuromuscular transmission.7. Histological examination of soleus showed atrophy of muscle fibres with normal preterminal axons. There was sprouting from motor nerve terminals and subsequently new motor end-plates were formed. These changes were not found in EDL.8. The results indicate that, in the mouse, tetanus toxin causes a presynaptic block of neuromuscular transmission and ;functional denervation' of muscle. Slow muscle is more sensitive to the effects of the toxin than fast.