NEURAL REGULATION OF MUSCLE ACETYLCHOLINESTERASE IS EXERTED ON THE LEVEL OF ITS MESSENGER-RNA

In rat muscles, AChE activity drops rapidly after denervation, and the patterns of AChE molecular forms in slow and fast muscles differ cons iderably. Both observations imply that muscle AChE is regulated by the motor nerve. In order to obtain a better insight into the underlying mechanism, AChE regulation in rat muscles was examined on the level of its catalytic subunit mRNA using northern blot analysis. The level of two AChE transcripts (2.4 and 3.2 kb) was much higher in the fast ste rnomastoid (STM) than in the slow soleus muscle, which explains the di fference in AChE activity between the two types of muscles. Expression of AChE mRNA in the extrajunctional region of STM muscle is fairly hi gh so that little difference in the level of AChE mRNAs was observed i n comparison to the region rich in the neuromuscular junctions. This i ndicates that very high AChE activity in the neuromuscular junctions i s achieved by unique posttranslational modifications and cellular proc essing of AChE enhancing stability of the junctional in comparison to the extrajunctional AChE. Denervation as well as botulinum toxin evoke d paralysis of STM muscle caused rapid decline of AChE transcripts to almost undetectable levels both in the junctional and extrajunctional regions. The low level of AChE mRNA is therefore largely responsible f or low AChE activity in denervated rat muscles. It seems that either m uscle activity and/or quantal ACh release enhance the level of AChE mR NA in the junctional as well as extrajunctional regions. In rat muscle s, extrajunctional mRNA level of the catalytic subunit of AChE is neur ally regulated in exact opposite fashion from that of acetylcholine re ceptor subunits. (C) 1994 Wiley-Liss, Inc.