Comprehensive Simulation of Ca2+ Transients in the Continuum of Mouse Skeletal Muscle Fiber Types

Mag-Fluo-4 has revealed differences in the kinetics of the Ca2+ transients of mammalian fiber types (I, IIA, IIX, and IIB). We simulated the changes in [Ca2+] through the sarcomere of these four fiber types, considering classical (troponin –Tn–, parvalbumin –Pv–, adenosine triphosphate –ATP–, sarcoplasmic reticulum Ca2+ pump –SERCA–, and dye) and new (mitochondria –MITO–, Na+/Ca2+ exchanger –NCX–, and store-operated calcium entry –SOCE–) Ca2+ binding sites, during single and tetanic stimulation. We found that during a single twitch, the sarcoplasmic peak [Ca2+] for fibers type IIB and IIX was around 16 µM, and for fibers type I and IIA reached 10–13 µM. The release rate in fibers type I, IIA, IIX, and IIB was 64.8, 153.6, 238.8, and 244.5 µM ms−1, respectively. Both the pattern of change and the peak concentrations of the Ca2+-bound species in the sarcoplasm (Tn, PV, ATP, and dye), the sarcolemma (NCX, SOCE), and the SR (SERCA) showed the order IIB ≥ IIX > IIA > I. The capacity of the NCX was 2.5, 1.3, 0.9, and 0.8% of the capacity of SERCA, for fibers type I, IIA, IIX, and IIB, respectively. MITO peak [Ca2+] ranged from 0.93 to 0.23 µM, in fibers type I and IIB, respectively, while intermediate values were obtained in fibers IIA and IIX. The latter numbers doubled during tetanic stimulation. In conclusion, we presented a comprehensive mathematical model of the excitation–contraction coupling that integrated most classical and novel Ca2+ handling mechanisms, overcoming the limitations of the fast- vs. slow-fibers dichotomy and the use of slow dyes.

Exercising muscle mass influences neuromuscular, cardiorespiratory, and perceptual responses during and following ramp incremental cycling to task failure

Neuromuscular (NM), cardiorespiratory, and perceptual responses to maximal graded exercise using different amounts of active muscle mass remain unclear. We hypothesized that during dynamic exercise, peripheral NM fatigue (declined twitch force) and muscle pain would be greater using smaller muscle mass, whereas central fatigue (declined voluntary activation) and ventilatory variables would be greater using larger muscle mass. Twelve males (29.8±4.7 years) performed two cycling ramp incremental tests until task failure: (i) single-leg (SL) with 10 W·min-1ramp, and (ii) double-leg (DL) with 20 W·min-1ramp. NM fatigue was assessed at baseline, task failure (post), then after 1, 4, and 8 min of recovery. Cardiorespiratory and perceptual variables (i.e., ratings of perceived exertion (RPE), fatigue, pain, dyspnea) were measured throughout cycling. Exercise duration was similar between sessions (SL: 857.7±263.6; DL: 855.0±218.8 s; p=0.923) and higher absolute peak power output was attained in DL (SL: 163.2±43.8; DL: 307.0±72.0 W; p<0.001). While central fatigue did not differ between conditions (SL: -6.6±6.5%; DL: -3.5±4.8%; p=0.091), maximal voluntary contraction (SL: -41.6±10.9%; DL: -33.7±8.5%; p=0.032) and single twitch forces (SL: -59.4±18.8%; DL: -46.2±16.2%; p=0.003) declined more following SL. DL elicited higher peak oxygen uptake (SL: 42.1±10.0; DL:50.3±9.3 mL·kg-1·min-1; p<0.001), ventilation (SL: 137.1±38.1; DL: 171.5±33.2 L·min-1; p<0.001), and heart rate (SL: 167±21; DL: 187±8 bpm; p=0.005). Dyspnea (p=0.025) was higher in DL; however, RPE (p=0.005) and pain (p<0.001) were higher in SL. These results suggest that interplay between NM, cardiorespiratory, and perceptual determinants of exercise performance during incremental cycling to task failure are muscle mass-dependent.

Slight power output manipulations around the maximal lactate steady state have an impact on fatigue in females and males.

Neuromuscular fatigue (NMF) and exercise performance are affected by exercise intensity and sex differences. However, whether slight changes in power output (PO) below and above the maximal lactate steady-state (MLSS) impact NMF and subsequent performance (time to exhaustion, TTE) is unknown. Purpose: This study compared NMF and TTE in females and males in response to exercise performed at MLSS, 10 W below (MLSS-10) and above (MLSS+10). Methods: Twenty participants (9 females) performed three 30-min constant-PO exercise bouts followed (1 min delay) by a TTE at 80% of the peak-PO. NMF was characterized by isometric maximal voluntary contractions (IMVC) and femoral nerve electrical stimulation of knee extensors [e.g. peak torque of potentiated high-frequency (Db100) and single twitch (TwPt)] before and immediately after the constant-PO and TTE bouts. Results: IMVC declined less after MLSS-10 (-18±10%) compared to MLSS (-26±14%) and MLSS+10 (-31±11%) (all p<0.05), and the Db100 decline was greater after MLSS+10 (-24±14%) compared to the other intensities (MLSS-10: -15±9%; MLSS: -18±11%) (all p<0.05). Females showed smaller reductions in IMVC and TwPt compared to males after constant-PO bouts (all p<0.05), this difference being not dependant on intensity. TTE was negatively impacted by increasing the PO in the constant-PO (p<0.001), with no differences in end-exercise NMF (p>0.05). Conclusion: Slight changes in PO around MLSS elicited great changes in the reduction of maximal voluntary force and impairments in contractile function. Although NMF was lower in females compared to males, the changes in PO around the MLSS impacted both sexes similarly.

Effects of whole-body vibrations on neuromuscular fatigue: a study with sets of different durations

Background Whole body vibrations have been used as an exercise modality or as a tool to study neuromuscular integration. There is increasing evidence that longer WBV exposures (up to 10 minutes) induce an acute impairment in neuromuscular function. However, the magnitude and origin of WBV induced fatigue is poorly understood. Purpose The study aimed to investigate the magnitude and origin of neuromuscular fatigue induced by half-squat long-exposure whole-body vibration intervention (WBV) with sets of different duration and compare it to non-vibration (SHAM) conditions. Methods Ten young, recreationally trained adults participated in six fatiguing trials, each consisting of maintaining a squatting position for several sets of the duration of 30, 60 or 180 seconds. The static squatting was superimposed with vibrations (WBV30, WBV60, WBV180) or without vibrations (SHAM30, SHAM60, SHAM180) for a total exercise exposure of 9-minutes in each trial. Maximum voluntary contraction (MVC), level of voluntary activation (%VA), low- (T20) and high-frequency (T100) doublets, low-to-high-frequency fatigue ratio (T20/100) and single twitch peak torque (TWPT) were assessed before, immediately after, then 15 and 30 minutes after each fatiguing protocol. Result Inferential statistics using RM ANOVA and post hoc tests revealed statistically significant declines from baseline values in MVC, T20, T100, T20/100 and TWPT in all trials, but not in %VA. No significant differences were found between WBV and SHAM conditions. Conclusion Our findings suggest that the origin of fatigue induced by WBV is not significantly different compared to control conditions without vibrations. The lack of significant differences in %VA and the significant decline in other assessed parameters suggest that fatiguing protocols used in this study induced peripheral fatigue of a similar magnitude in all trials.

Subparalyzing Doses of Rocuronium Reduce Muscular Endurance without Detectable Effect on Single Twitch Height in Awake Subjects

Purpose. To test the hypothesis that a low-dose rocuronium acts mainly by means of reducing muscular endurance rather than by reducing momentary force. Methods. In a randomized placebo-controlled double-blinded study, eight healthy volunteers were studied in two sets of experiments. In the first set, the subjects made a sustained maximum effort with the dominant hand for 80 seconds while squeezing an electronic handgrip dynamometer at three minutes after intravenous administration of placebo, 0.04 or 0.08 mg/kg rocuronium. Handgrip force at initiation of testing (maximum handgrip force) and after 60 seconds was evaluated. In the second set, the ulnar nerve of the subjects was electrically stimulated every tenth second for at least 10 and a maximum of 30 minutes following the administration of placebo and 0.08 mg/kg rocuronium. Single twitch height of the adductor pollicis muscle was recorded. Results. There was no significant difference in the effect on maximum handgrip force at time 0 between the three different doses of rocuronium. As compared with placebo, handgrip force after 0.08 mg/kg rocuronium was reduced to approximately a third at 60 seconds (214 N (120–278) vs. 69 (30–166); p=0.008), whereas only a slight reduction was seen after 0.04 mg/kg (187 (124–256); p=0.016). Based on these results, the sustained handgrip force after 0.2 mg/kg at 60 seconds was calculated to be 1.27% (95% CI [0.40, 4.03]) of the maximum force of placebo. No effect on single twitch height after 0.08 mg/kg rocuronium at four minutes after drug administration could be detected. Conclusions. Subparalyzing doses of rocuronium show a distinct effect on muscular endurance as opposed to momentary force. The findings support the hypothesis that low doses of rocuronium act mainly by reducing muscular endurance, thereby facilitating, for example, tracheal intubation.

Resting shear elastic modulus as a marker of peripheral fatigue during maximal isometric contractions in humans

The aim of this study was to investigate whether the resting Vastus Lateralis (VL) muscle shear elastic modulus (µ), evaluated by shear wave elastography, represents peripheral fatigue during repetition of isometric maximal voluntary contractions (MVCs) of the knee extensor (KE) muscles.Eight healthy well-trained males repeated 60 isometric MVCs of the KE muscles (6 × 10 MVCs; 5 s on/5 s off). Single and double electrical stimulations were delivered to the femoral nerve every ten MVCs during contraction and at rest. The amplitude and properties of the potentiated torque following single (Twpot) double electrostimulation and the amplitude of the concomitant VL compound action potential were considered to be indicators of peripheral fatigue. The resting VLµ was measured during a 5-s rest period after each MVC and electrical stimulation series.The resting VLµ significantly decreased (-21.8 ± 3.9%; P < 0.001) by the end of the fatigue protocol, decreasing from the 10th MVC to the end of the exercise (60th MVC) for all participants, with the loss ranging from 18 to 29%. The potentiated doublet and single twitch torque (Twpot) decreased by 42.5 ± 10.8% and 55.7 ± 8.8%, respectively, by the end of exercise (P < 0.001 for both). The relative mechanical properties of Twpot, i.e. electromechanical delay (P <0 .001), contraction time (P = 0.004), and maximal rate of torque development/relaxation (P < 0.001) also changed significantly during exercise.This study shows that the kinetics of the resting VLµ is associated with changes in both voluntary and electrostimulated torque amplitudes and electromechanical properties of the single twitch during the repetition of maximal voluntary fatiguing exercise. Changes in the resting VLµ may reflect a decline in muscle function, e.g. impairment of excitation-contraction coupling, contractile processes, and/or elastic properties, throughout the increase in muscle compliance, directly affecting force transmission.