Muscle Torque-Velocity Relationships and Fatigue With Reduced Knee Joint Range of Motion in Young and Older Adults.

The purpose of this study was to evaluate the influence of knee joint range of motion (RoM) on the torque-velocity relationship and fatigue in the knee extensor muscles of 7 young (median = 26 y) and 7 older (68 y) adults. Each leg was assigned a RoM (35° or 75°) over which to perform a torque-velocity protocol (maximal isokinetic contractions, 60-300°·s-1) and a fatigue protocol (120 maximal contractions at 120°·s-1, 0.5 Hz). Six older participants were unable to reach 300°·s-1 over 35°. Therefore, the velocity eliciting 75% of peak torque at 60°·s-1 (V75, °·s-1) was calculated for each RoM from a fit of individual torque-velocity curves (60-240°·s-1), and ΔV75 (35°-75°) was determined. Fatigue (final torque/initial torque) was used to calculate Δfatigue (35°-75°). ΔV75 was not different from 0 in young (-28.3°·s-1 [-158.6 to 55.7], median [range], P = .091) or older (-18.5°·s-1 [-95.0 to 23.9], P = .128), with no difference by age (P = .710). In contrast, fatigue was greater for 75° in young (Δfatigue = 25.9% [17.5-30.3], P = .018) and older (17.2% [11.9-52.9], P = .018), with no effect of age (P = .710). These data indicate that, regardless of age, RoM did not alter the torque-velocity relationship between 60 and 240°·s-1, and fatigue was greater with a larger RoM.

Postcontraction [acetylcarnitine] reflects interindividual variation in skeletal muscle ATP production patterns in vivo.

In addition to its role in substrate selection (carbohydrate vs. fat) for oxidative metabolism in muscle, acetylcarnitine production may be an important modulator of the energetic pathway by which ATP is produced. A combination of noninvasive magnetic resonance spectroscopy measures of cytosolic acetylcarnitine and ATP production pathways was used to investigate the link between [acetylcarnitine] and energy production in vivo. Intracellular metabolites were measured in the vastus lateralis muscle of eight males (mean: 28.4 yr, range: 25-35) during 8 min of incremental, dynamic contractions (0.5 Hz, 2-min stages at 6%, 9%, 12%, and 15% maximal torque) that increased [acetylcarnitine] approximately fivefold from resting levels. ATP production via oxidative phosphorylation, glycolysis, and the creatine kinase reaction was calculated based on phosphorus metabolites and pH. Spearman rank correlations indicated that postcontraction [acetylcarnitine] was positively associated with both absolute (mM) and relative (% total ATP) glycolytic ATP production (rs = 0.95, P = 0.001; rs = 0.93, P = 0.002), and negatively associated with relative (rs = -0.81, P = 0.02) but not absolute (rs = -0.14, P = 0.75) oxidative ATP production. Thus, acetylcarnitine accumulated more when there was a greater reliance on "nonoxidative" glycolysis and a relatively lower contribution from oxidative phosphorylation, reflecting the fate of pyruvate in working skeletal muscle. Furthermore, these data indicate striking interindividual variation in responses to the energy demand of submaximal contractions. Overall, the results of this preliminary study provide novel evidence of the coupling in vivo between ATP production pathways and the carnitine system.NEW & NOTEWORTHY Production of acetylcarnitine from acetyl-CoA and free carnitine may be important for energy pathway regulation in contracting skeletal muscle. Noninvasive magnetic resonance spectroscopy was used to investigate the link between acetylcarnitine and energy production in the vastus lateralis muscle during dynamic contractions (n = 8 individuals). A positive correlation between acetylcarnitine accumulation and "nonoxidative" glycolysis and an inverse relationship with oxidative phosphorylation, provides novel evidence of the coupling between ATP production and the carnitine system in vivo.

Correction: Distribution of vesicle pools in cerebellar parallel fibre terminals after depression of ectopic transmission.

[This corrects the article DOI: 10.1371/journal.pone.0200937.].

Distribution of vesicle pools in cerebellar parallel fibre terminals after depression of ectopic transmission.

At parallel fibre terminals in the cerebellar cortex, glutamate released outside of the active zone can activate AMPA receptors on juxtaposed Bergmann glial cell processes. This process is termed "ectopic" release, and allows for directed transmission to astroglial cells that is functionally independent of synaptic transmission to postsynaptic Purkinje neurons. The location of ectopic sites in presynaptic terminals is uncertain. Functional evidence suggests that stimulation of parallel fibres at 1 Hz exhausts ectopic transmission due to a failure to rapidly recycle vesicles to the ectopic pool, and so would predict a loss of vesicles in the near vicinity of extrasynaptic glial processes. In this study we used this stimulation protocol to investigate whether the distribution of vesicles within the presynaptic terminal is altered after suppression of ectopic release. Stimulation at 1 Hz had only a minor impact on the distribution of vesicles in presynaptic terminals when analysed with electron microscopy. Vesicle number and terminal size were unaffected by 1 Hz stimulation, but the relative abundance of vesicles in close proximity to the active zone was marginally reduced. In contrast, the fraction of vesicles facing glial membranes was unchanged after suppression of ectopic transmission. 1 Hz stimulation also resulted in a small but statistically-significant increase in the distance between glial membrane and presynaptic terminal, suggesting withdrawal of glial membranes from synapses is detectable in ultrastructural anatomy within minutes. These results raise doubts about the location of ectopic release sites, but indicate that neuron-glial association varies on a dynamic time scale.