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The Journal of Neuroscience, March 15, 1998, 18(6):1944-1952
Acetylcholinesterase mRNA Level and Synaptic Activity in Rat
Muscles Depend on Nerve-Induced Pattern of Muscle Activation
Janez
Sketelj1,
Neva
rne-Finderle1,
Borut
trukelj2,
Jo e V.
Trontelj3, and
Dirk
Pette4
1 Institute of Pathophysiology, School of Medicine,
University of Ljubljana, 1000 Ljubljana, Slovenia, 2 Jozef
Stefan Institute, 1000 Ljubljana, Slovenia, 3 Institute of
Clinical Neurophysiology, University Medical Center, 1000 Ljubljana,
Slovenia, and 4 Fakultät für Biologie,
Universität Konstanz, D-78457 Konstanz Germany
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 applied to fast muscles in rats. Molecular forms of AChE
were analyzed by velocity sedimentation, and AChE mRNA levels were
analyzed by Northern 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
A12 AChE form in 35 d stimulated fast muscles decreased to
56% of control value, reaching that in the soleus muscle. Therefore,
synaptic AChE itself depends on the muscle activation pattern. Complete
inactivity after denervation also decreased the AChE mRNA level in fast
muscles to <10% in 48 hr. In contrast, profuse fibrillations observed
in noninnervated immature regenerating muscles maintain AChE mRNA
levels at 80% of that in the innervated fast muscles. If protein
synthesis was inhibited by cycloheximide, AChE mRNA levels in 3-d-old
regenerating muscle, still containing myoblasts, increased
approximately twofold. No significant increase after cycloheximide
application was observed either in denervated mature fast muscles or in
normal slow muscles. Low AChE mRNA levels observed in those muscles are
probably not caused by decreased stability of AChE mRNA as demonstrated
in myoblasts.
Key words:
acetylcholinesterase; denervation; muscle; muscle
stimulation; nerve-muscle interaction; nerve impulse pattern; neuromuscular junction; plasticity; regeneration; synapse
Copyright © 1998 Society for Neuroscience 0270-6474/98/1861944-09$05.00/0
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