Sensitivity of subcellular components of neuromuscular junctions to decreased neuromuscular activity

Abstract

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. 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. It was also discovered that unloading decreased the area of calcium channels 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 the weight‐bearing soleus fibers, where no subcellular remodeling was evident, was noted. 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.

Effects of short‐term unloading and active recovery on human motor unit properties, neuromuscular junction transmission and transcriptomic profile

“…Conversely, seminal studies conducted in animal models have shown NMJ alterations in response to both total disuse (induced by denervation or synaptic blockade via toxin application) (Brown & Ironton, 1977;Eldridge et al, 1981;Labovitz et al, 1984;Pestronk & Drachman, 1978;Pestronk et al, 1976) and partial disuse (muscle unloading, such as hindlimb suspension) (Deschenes & Wilson, 2003;Fahim, 1989;Fahim & Robbins, 1986;Pachter & Eberstein, 1984). In particular, previous work reported changes in endplate size (Deschenes & Wilson, 2003;Eldridge et al, 1981;Labovitz et al, 1984;Pestronk & Drachman, 1978), postsynaptic fold structure (Fahim, 1989;Labovitz et al, 1984), subcellular active zones (Deschenes et al, 2021), acetylcholine (ACh) receptor distribution (i.e. increased expression of extrasynaptic ACh receptors) and density (Eldridge et al, 1981;Pestronk & Drachman, 1978;Pestronk et al, 1976), and nerve terminal sprouting (Eldridge et al, 1981;Fahim & Robbins, 1986;Pestronk & Drachman, 1978;Pestronk et al, 1976).…”

Ladder-based resistance training with the progression of training load altered the tibial nerve ultrastructure and muscle fiber area without altering the morphology of the postsynaptic compartment

“…The NMJ region is susceptible to stimuli or their absence ( Wilson and Deschenes, 2005 ; Krause Neto et al, 2015 ; Deschenes et al, 2021 ; Deschenes et al, 2022 ). However, we demonstrated that none of the LRT protocols could elicit morphological changes in the motor endplate of any of the evaluated muscles.…”

“…Recent work has suggested that the increase or absence of stimuli can elicit changes in the neuromuscular system ( Wilson and Deschenes, 2005 ; Krause Neto et al, 2017 ; Deschenes et al, 2021 ; Krause Neto et al, 2021 ; Deschenes and Stock, 2022 ; Krause Neto et. 2015 ).…”