Junctional and extrajunctional acetylcholinesterase in skeletal muscle fibers

The asymmetric A12 acetylcholinesterase (AChE) molecular form, consisting of three tetrameric catalytic oligomers and three non-catalytic subunits of collagen Q (ColQ), is the functional AChE form in the neuromuscular junction. Its extremely high concentration and sharp localization in the junction is mostly due to the binding of this AChE form to perlecan in the synaptic basal lamina. In the rat neuromuscular junctions, about two-thirds of AChE molecules appear to be bound by ionic interactions involving calcium and the rest is probably bound covalently. In immature rat muscles, the A12 AChE forms are expressed also extrajunctionally. During the early post-natal period, this expression is completely suppressed in rat fast muscles, whereas it extends into adulthood in the slow soleus muscles because of the differences in the extrajunctional expression of ColQ between fast and slow muscles. The level of the A12 molecular forms of AChE in the extrajunctional muscle regions is regulated by the motor nerve, probably via the pattern of muscle fibre activations triggered by the nerve. The pattern of muscle activations also regulates the extrajunctional expression of the catalytic subunits of AChE: phasic, infrequent, high frequency activations enhance expression, whereas prolonged tonic low-frequency activations tend to decrease it. Calcineurin signalling pathway seems to be involved.