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

Abstract

A sublethal quantity of black widow spider venom was injected into the calf muscles of mice. After 30 min to 6 soleus muscles were examined by light microscopy and EM and by electrophysiological techniques. Within 30 min motor nerve terminals were swollen and depleted of 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. 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. Physiological study showed complete failure of transmission and absence of miniature end-plate potentials (MEPP) and end-plate potentials (EPP) until day 3, when muscles responded weakly to indirect stimulation and MEPP were recorded at 30% and EPP at 40% of fibers. The mean quantal content of EPP 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. The proportion of fibers at which MEPP and EPP were recorded returned to normal by day 6 and mean quantal content was normal by day 9. 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.