Sensitivity of subcellular components of neuromuscular junctions to decreased neuromuscular activity

Introduction/Aims

Muscle unloading imparts subtotal disuse on the neuromuscular system resulting in reduced performance capacity. This loss of function, at least in part, can be attributed to disruptions at the neuromuscular junction (NMJ). However, research has failed to document morphological remodeling of the NMJ with short term muscle unloading. Here, rather than quantifying cellular components of the NMJ, we examined subcellular active zone responses to 2 weeks of unloading in male Wistar rats.

Methods

The hindlimb suspension model was used to impart unloading. Following this intervention, animals were euthanized, and immunofluorescent procedures were used to visualize, and quantify active zones and endplates of the NMJ.

Results

It was revealed that in the plantaris, but not the soleus muscles, unloading elicited significant (P ≤ 0.05) decrements in active zone staining as measured by Bassoon, and calcium channel expression. Also it was discovered that unloading decreased the area of calcium channel staining relative to active zone areas of staining suggesting potential interference in the ability of calcium influx to trigger the release of vesicles docked at the active zone. Post-synaptic adaptations of the motor endplate were not evident. This presynaptic subcellular size reduction was not associated with atrophy of the underlying plantaris muscle fibers, although atrophy of weight-bearing soleus fibers, where no subcellular remodeling was evident, was noted.

Discussion

These results suggest that the active zone is highly sensitive to alterations in neuromuscular activity, and that morphological adaptation of excitatory and contractile components of the NMJ can occur independently of each other.

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