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.