Control of junctional acetylcholinesterase by neural and muscular influences in the rat.

Abstract

The development of AChE [acetylcholinesterase] at ectopic neuromuscular junctions forming between a transplanted foreign nerve (the superficial fibular nerve) and the denervated soleus muscle was studied in adult rats. Junctional AChE activity began to appear in the vicinity of the fibular nerve sprouts 6-7 days after section of the soleus nerve and 3-4 days after the onset of transmission. No histochemically detectable AChE appeared when the fibular nerve was cut 0-4 days after the soleus nerve had been cut. Direct electrical stimulation of the denervated soleus muscle caused plaques of true AChE, as determined by inhibitor studies, to appear in muscles where the fibular nerve had been cut 2-4 days after the soleus nerve but not in muscles where the 2 nerves were cut at the same time. The plaques appeared only in the vicinity of fibular nerve sprouts and coincided with newly formed but stable peaks of ACh sensitivity. Local application of Neostigmine prolonged and increased the depolarizing responses evoked by pulses of ACh at these sites. In muscles where the fibular nerve was intact the AChE plaques changed gradually over a few weeks from an immature appearance to a mature appearance characteristic of normal end-plates. In stimulated muscles where the fibular nerve was cut the plaques stained intensely but remained morphologically immature. Muscle activity is probably important for the appearance of AChE at developing neuromuscular junctions. AChE may accumulate only at sites on the muscle surface where the nerve fibres have left a trace upon contact with the muscle fibers. These traces form quickly and persist after nerve-muscle interaction of as little as 2 days. The muscle appears as a major source of junctional AChE since stimulation of the muscle induces intense AChE activity in muscles where the nerve has degenerated.