Neural regulation of muscle acetylcholinesterase is exerted on the level of its mRNA.
In rat muscles, AChE activity drops rapidly after denervation, and the patterns of AChE molecular forms in slow and fast muscles differ considerably. 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 sternomastoid (STM) than in the slow soleus muscle, which explains the difference in AChE activity between the two types of muscles. Expression of AChE mRNA in the extrajunctional region of STM muscle is fairly high so that little difference in the level of AChE mRNAs was observed in comparison to the region rich in the neuromuscular junctions. This indicates that very high AChE activity in the neuromuscular junctions is achieved by unique posttranslational modifications and cellular processing of AChE enhancing stability of the junctional in comparison to the extrajunctional AChE. Denervation as well as botulinum toxin evoked 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 for low AChE activity in denervated rat muscles. It seems that either muscle activity and/or quantal ACh release enhance the level of AChE mRNA in the junctional as well as extrajunctional regions. In rat muscles, extrajunctional mRNA level of the catalytic subunit of AChE is neurally regulated in exact opposite fashion from that of acetylcholine receptor subunits.
Cresnar
B
B
Institute of Pathophysiology, School of Medicine, University of Ljubljana, Slovenia.
Crne-Finderle
N
N
Breskvar
K
K
Sketelj
J
J
D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000302:isolation & purification; D000818:Animals; D015152:Blotting, Northern; D001905:Botulinum Toxins / Q000494:pharmacology; D008297:Male; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000294:innervation; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D000110:Acetylcholinesterase; D001905:Botulinum Toxins