ACETYLCHOLINESTERASE MESSENGER-RNA LEVEL AND SYNAPTIC ACTIVITY IN RATMUSCLES DEPEND ON NERVE-INDUCED PATTERN OF MUSCLE ACTIVATION

Acetylcholinesterase (AChE) mRNA levels are severalfold higher in fast rat muscles compared with slow. We hypothesized that AChE mRNA levels and AChE activity in the neuromuscular junction depend on a specific nerve-induced pattern of motor unit activation. Chronic low-frequency stimulation, mimicking the activation pattern in slow muscles, was app lied to fast muscles in rats, Molecular forms of AChE were analyzed by velocity sedimentation, and AChE mRNA levels were analyzed by Norther n blots. AChE mRNA levels in stimulated fast muscles dropped to 10-20% of control after 1 week and became comparable to those in slow soleus muscles. The activity of the junctional A(12) AChE form in 35 d stimu lated fast muscles decreased to 56% of control value, reaching that in the soleus muscle. Therefore, synaptic AChE itself depends on the mus cle activation pattern. Complete inactivity after denervation also dec reased the AChE mRNA level in fast muscles to <10% in 48 hr, In contra st, profuse fibrillations observed in noninnervated immature regenerat ing muscles maintain AChE mRNA levels at 80% of that in the innervated fast muscles, If protein synthesis was inhibited by cycloheximide, AC hE mRNA levels in 3-d-old regenerating muscle, still containing myobla sts, increased approximately twofold, No significant increase after cy cloheximide application was observed either in denervated mature fast muscles or in normal slow muscles. Low AChE mRNA levels observed in th ose muscles are probably not caused by decreased stability of AChE mRN A as demonstrated in myoblasts.