Sensitivity of subcellular components of neuromuscular junctions to decreased neuromuscular activity.

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 exercise training on neuromuscular junctions and their active zones in young and aged muscles.

The neuromuscular junction (NMJ) connects the motor neuron with myofibers allowing muscle contraction. Both aging and increased activity result in NMJ remodeling. Here, the effects of exercise were examined in young and aged soleus muscles. Using immunofluorescent staining procedures, cellular and active zone components of the NMJ were quantified following a treadmill running program. Immunofluorescence was employed to determine myofiber profiles (size and type). Two-way analysis of variance procedures with main effects of age and treatment showed that when analyzing NMJs at the cellular level, significant (p ≤ 0.05) effects were identified for age, but not treatment. However, when examining subcellular active zones, effects for exercise, but not for age, were detected. Myofiber cross-sectional area showed that aging elicited atrophy and that among younger muscles endurance exercise training yielded decrements in myofiber size. Conversely, among aged muscles training elicited whole muscle and myofiber trends (p < 0.10) toward hypertrophy. Thus, different components of the neuromuscular system harbor unique sensitivities to various stimuli enabling proper adaptations to attain optimal function under differing conditions.

Both aging and exercise training alter the rate of recovery of neuromuscular performance of male soleus muscles.

It is known that both exercise and aging influence neuromuscular performance; however their effects on post-exercise recovery are largely unknown. To examine how exercise training and aging might affect post-exercise recovery, the function of muscles taken from young, and aged male rats assigned to exercise, or control conditions was assessed with ex vivo procedures using indirect (nerve endings), and direct (sarcolemma) stimulation at different times (Initial, Final min of, and Recovery i.e. 1 min post, from 5 min of stimulation). Results revealed that initially, strength of indirectly stimulated young, male muscles was significantly (P = 0.05) greater than aged ones, but after continuous stimulation, aged and young muscles displayed similar strength, and controls showed more strength than trained muscles (P = 0.02). All groups except young controls exhibited significant recovery with 1 min of rest (P = 0.03). Compared to indirect stimulation, direct stimulation resulted in greater peak tension at each time point examined (P < 0.05); young muscles again were stronger than aged ones initially (P = 0.003), but not by the conclusion of stimulation (P = 0.20). One min following the direct stimulation protocol, no significant recovery was observed by any of the four treatment groups. These data indicate that motor neurons limit neuromuscular function, and that the effects of fatigue are more severe during stimulation of young, compared to aged muscle. Finally, results presented here indicate that age and training status do interact to influence post-exertional recovery, at least among male neuromuscular systems.