COMPARISON BETWEEN THE EFFECTS OF BOTULINUM TOXIN-INDUCED PARALYSIS AND DENERVATION ON MOLECULAR-FORMS OF ACETYLCHOLINESTERASE IN MUSCLES

Velocity sedimentation analysis of acetylcholinesterase (AChE) molecul ar forms in the fast extensor digitorum longus muscle and in the slow soleus muscle of the rat was carried out on days 4, 8, and 14 after in duction of muscle paralysis by botulinum toxin type A (BoTx). The resu lts were compared with those observed after muscle denervation. In add ition, the ability of BoTx-paralyzed muscles to resynthesize AChE was studied after irreversible inhibition of the preexistent enzyme by dii sopropyl phosphorofluoridate. Major differences were observed between the effects of BoTx treatment and nerve section on AChE in the junctio nal region of the muscles. A precipitous drop in content of the asymme tric A12 AChE form was observed after denervation, whereas its decreas e was much slower and less extensive in the BoTx-paralyzed muscles. Re covery of junctional AChE and of its Al 2 form after irreversible inhi bition of the preexistent AChE in BoTx-paralyzed muscles was neverthel ess very slow. It seems that a greater part of the junctional Al 2 ACh E form pertains to a fraction with a very slow turnover that is rapidl y degraded after denervation but not after BoTx-produced muscle paraly sis. The postdenervation decrease in content of junctional Al 2 AChE i s therefore not primarily due to muscle inactivity. The extrajunctiona l molecular forms of AChE seem to be regulated mostly by muscle activi ty because they undergo virtually identical changes both after denerva tion and BoTx paralysis. The differences observed in this respect betw een the fast and slow muscles after their inactivation must be intrins ic to muscles.