The neuromuscular junction of the mouse after black widow spider venom.

1. A sublethal quantity of black widow spider venom was injected into the calf muscles of mice. After 30 min to 6 weeks soleus muscles were examined by light and electron microscopy and by electrophysiological techniques. 2. Within 30 min motor nerve terminals were swollen and depleted for synaptic vesicles and by 6 h were disrupted and engulfed by Schwann cells. By 24 h every end-plate examined was denervated. Some preterminal myelinated axons also showed degenerative changes. 3. Re-innervation was first seen at 2 days. By 3 days axon terminals were present at most end-plates and by 8 days their morphology was nearly normal. The normal pattern of innervation of the muscle was re-established in that axons re-innervated their original end-plates and very few ultraterminal axonal sprouts were found. 4. Physiological study showed complete failure of transmission and absence of miniature end-plate potentials (m.e.p.p.s) and end-plate potentials (e.p.p.s) until day 3, when muscles responded weakly to indirect stimulation and m.e.p.p.s were recorded at 30% and e.p.p.s at 40% of fibres. The mean quantal content of e.p.p.s was low and there was rapid fatigue on repetitive stimulation. Extrajunctional sensitivity to acetylcholine developed within 1 day, was maximal at 3 days and declined to normal at 12-14 days. 5. The proportion of fibres at which m.e.p.p.s and e.p.p.s were recorded returned to normal by day 6 and mean quantal content was normal by day 9. 6. These findings show that the re-innervation of original end-plates is of importance in facilitating the rapid return of transmission to normal levels and limiting the extent of axonal growth.