REINNERVATION OF A DENERVATED SLOW MUSCLE TRIGGERS HIGH EXTRAJUNCTIONAL EXPRESSION OF THE ASYMMETRIC MOLECULAR-FORMS OF ACETYLCHOLINESTERASE

Expression of acetylcholine receptor and of the asymmetric molecular f orms of acetylcholinesterase (AChE) in the extrajunctional regions of rat muscles is suppressed during early postnatal development. In matur e muscles, the extrajunctional synthesis of acetylcholine receptor, bu t not of the asymmetric molecular forms of AChE, becomes reactivated a fter denervation. The hypothesis that a denervated muscle needs reinne rvation in order to revert transiently to an immature state characteri zed by high extrajunctional production of the asymmetric AChE forms, w as examined in rat muscles recovering after nerve crush. Molecular for ms of AChE were analysed by velocity sedimentation, Activity of the as ymmetric A(12) AChE form in the extrajunctional regions of the slow so leus (SOL) muscle increased during the first week after reinnervation to about 9 times its control level, remained high for about one week, and declined towards normal thereafter. If the nerve was crushed close to the muscle and reinnervation occured very rapidly, the extrajuncti onal increase of the A(12) AChE form still occured but was less pronou nced than after late reinnervation. In contrast, a transient paralysis of the SOL muscle due to acetylcholine receptor blockade by a-bungaro toxin, followed by spontaneous recovery of muscle activity after 3-5 d ays, did not revert AChE regulation into an immature state. Disuse of the SOL muscle caused by leg immobilization, which is known to change the tonic pattern of neural stimulation of the SOL muscle into a phasi c one, did not prevent the reversion of AChE regulation during reinner vation. This indicates that neural stimulation pattern is not crucial for this reversion. In contrast to slow SOL, the fast extensor digitor um longus muscle did not revert to an immature state in respect to ACh E regulation after reinnervation. This muscle type-specific response m ay be due to intrinsic differences between the myogenic cells of slow and fast muscle fibres. (C) 1995 Wiley-Liss, Inc.