Exercise modulates synaptic acetylcholinesterase at neuromuscular junctions

•Fast-walk training elevated acetylcholinesterase in rat fast-twitch leg muscles.•Exercise increased membrane-bound tetramers while other isoforms remained unchanged.•Training elevated acetylcholinesterase but not receptors at neuromuscular junctions.•Exercise-added enzyme inserted on the muscle-side of the synaptic cleft and folds.

Acetylcholinesterase plays a major role in neuromuscular transmission and is regulated by neuromuscular activity. Since fast-twitch motor units are recruited with increased motor demand, we examined acetylcholinesterase regulation in rat leg muscles following treadmill training. Total acetylcholinesterase and specifically the membrane-bound tetramer increased in exercised fast-, but not slow-twitch muscles, while other isoforms remained unchanged. Synaptic acetylcholinesterase increased markedly in neuromuscular junctions of trained fibers, without concomitant changes in synaptic acetylcholine receptor, thus elevating synaptic acetylcholinesterase/receptor ratios. Electron microscopy showed that acetylcholinesterase increased in postjunctional folds and primary cleft, where it was added adjacent to the postsynaptic muscle membrane. Thus, although the primary acetylcholinesterase at the neuromuscular junction is the collagen-tailed asymmetric isoform associated with synaptic basal lamina, physiological demands such as strenuous exercise, or potentially pathological conditions, can selectively recruit the membrane-bound acetylcholinesterase tetramer to the synapse for optimal synaptic transmission.