Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles

Maximum shortening velocity ( V ₀) was determined in single fibres dissected from hind limb skeletal muscles of rabbit and mouse and classified according to their myosin heavy chain (MHC) isoform composition. The values for rabbit and mouse V ₀ were compared with the values previously obtained in man and rat under identical experimental conditions. Significant differences in V ₀ were found between fibres containing corresponding myosin isoforms in different species: as a general rule for each isoform V ₀ decreased with body mass. Myosin isoform distributions of soleus and tibialis anterior were analysed in mouse, rat, rabbit and man: the proportion of slow myosin generally increased with increasing body size. The diversity between V ₀ of corresponding myosin isoforms and the different myosin isoform composition of corresponding muscles determine the scaling of shortening velocity of whole muscles with body size, which is essential for optimisation of locomotion. The speed of actin translocation ( V _f) in in vitro motility assay was determined with myosins extracted from single muscle fibres of all four species: significant differences were found between myosin isoforms in each species and between corresponding myosin isoforms in different species. The values of V ₀ and V _f determined for each myosin isoform were significantly correlated, strongly supporting the view that the myosin isoform expressed is the major determinant of maximum shortening velocity in muscle fibres.     

Defective regulation of contractile function in muscle fibres carrying an E41K β-tropomyosin mutation

A novel E41K β-tropomyosin (β-Tm) mutation, associated with congenital myopathy and muscle weakness, was recently identified in a woman and her daughter. In both patients, muscle weakness was coupled with muscle fibre atrophy. It remains unknown, however, whether the E41K β-Tm mutation directly affects regulation of muscle contraction, contributing to the muscle weakness. To address this question, we studied a broad range of contractile characteristics in skinned muscle fibres from the two patients and eight healthy controls. Results showed decreases (i) in speed of contraction at saturated Ca²⁺ concentration (apparent rate constant of force redevelopment ( k _tr) and unloaded shortening speed ( V ₀)); and (ii) in contraction sensitivity to Ca²⁺ concentration, in fibres from patients compared with controls, suggesting that the mutation has a negative effect on contractile function, contributing to the muscle weakness. To investigate whether these negative impacts are reversible, we exposed skinned muscle fibres to the Ca²⁺ sensitizer EMD 57033. In fibres from patients, 30 μ m of EMD 57033 (i) had no effect on speed of contraction ( k _tr and V ₀) at saturated Ca²⁺ concentration but (ii) increased Ca²⁺ sensitivity of contraction, suggesting a potential therapeutic approach in patients carrying the E41K β-Tm mutation.     

Effects of a R133W β-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres

A novel R133W β-tropomyosin (β-Tm) mutation, associated with muscle weakness and distal limb deformities, has recently been identified in a woman and her daughter. The muscle weakness was not accompanied by progressive muscle wasting or histopathological abnormalities in tibialis anterior muscle biopsy specimens. The aim of the present study was to explore the mechanisms underlying the impaired muscle function in patients with the β-Tm mutation. Maximum force normalized to fibre cross-sectional area (specific force, SF), maximum velocity of unloaded shortening ( V ₀), apparent rate constant of force redevelopment ( k _tr) and force–pCa relationship were evaluated in single chemically skinned muscle fibres from the two patients carrying the β-Tm mutation and from healthy control subjects. Significant differences in regulation of muscle contraction were observed in the type I fibres: a lower SF ( P < 0.05) and k _tr ( P < 0.01), and a faster V ₀ ( P < 0.05). The force–pCa relationship did not differ between patient and control fibres, indicating an unaltered Ca²⁺ activation of contractile proteins. Collectively, these results indicate a slower cross-bridge attachment rate and a faster detachment rate caused by the R133W β-Tm mutation. It is suggested that the R133W β-Tm mutation induces alteration in myosin–actin kinetics causing a reduced number of myosin molecules in the strong actin-binding state, resulting in overall muscle weakness in the absence of muscle wasting.     

Change in contractile properties of human muscle in relationship to the loss of power and slowing of relaxation seen with fatigue

Slow relaxation from an isometric contraction is characteristic of acutely fatigued muscle and is associated with a decrease in the maximum velocity of unloaded shortening ( V _max) and both these phenomena might be due to a decreased rate of cross bridge detachment. We have compared the change in relaxation rate with that of various parameters of the force–velocity relationship over the course of an ischaemic series of fatiguing contractions and subsequent recovery using the human adductor pollicis muscle working in vivo at approximately 37°C in nine healthy young subjects. Maximal isometric force ( F ₀) decreased from 91.0 ± 1.9 to 58.3 ± 3.5 N (mean ± s.e.m. ). Maximum power decreased from 53.6 ± 4.0 to 17.7 ± 1.2 (arbitrary units) while relaxation rate declined from −10.3 ± 0.38 to −2.56 ± 0.29 s⁻¹. V _max showed a smaller relative change from 673 ± 20 to 560 ± 46 deg s⁻¹ and with a time course that differed markedly from that of slowing of relaxation, showing very little change until late in the series of contractions. Curvature of the force–velocity relationship increased ( a/F ₀ decreasing from 0.22 ± 0.02 to 0.11 ± 0.02) with fatigue and with a time course that was similar to that of the loss of power and the slowing of relaxation. It is concluded that for human muscle working at a normal physiological temperature the change in curvature of the force–velocity relationship with fatigue is a major cause of loss of power and may share a common underlying mechanism with the slowing of relaxation from an isometric contraction.     

Heterologous expression of wild-type and mutant β-cardiac myosin changes the contractile kinetics of cultured mouse myotubes

The properties of myosin expressed in muscle are a major determinant of muscle performance. In this study we used a novel approach to examine the functional impact of changes in myosin heavy chain (MHC) isoform expression, as well as the consequences of expressing the mutant MHC implicated in familial hypertrophic cardiomyopathy (FHC). Cultured mouse myoblasts that normally express fast embryonic myosin were untransfected, or stably transfected with a plasmid expressing either wild-type (cWT) or mutant (D778G or G741R) β-cardiac myosin. After differentiation for 5–7 days, cWT or mutant β-cardiac myosin was expressed at 25 % of total myosin in the myotube. We measured time-to-peak shortening (ttp), time for half-relaxation ( t _0.5), the maximum velocity of shortening ( V _max) at 1 Hz stimulation, and the tetanic fusion frequency. Expression of cWT β-cardiac myosin significantly increased ttp and t _0.5 and decreased the fusion frequency compared with untransfected myotubes. However, when we compared myotubes expressing mutant β-cardiac myosin with those expressing cWT β-cardiac myosin, we found that ttp and t _0.5 were significantly decreased, and V _max was increased for the D778G mutant, whereas ttp, t _0.5 and V _max were unchanged for the G741R mutant. The fusion frequency was increased for both mutant myosins. Our data support the conclusion that the impact of the slower myosin isoform dominates when both slow and fast isoforms are present. This work suggests that FHC associated with either D778G or G741R mutation in MHC is an 'energy cost' disease, but that the phenotype of D778G is more severe than that of G741R.     

Response linearity in primary auditory cortex of the ferret

The responses of neurons within the primary auditory cortex (A1) of the ferret elicited by broadband dynamic spectral ripple stimuli were examined over a range of ripple spectral densities and ripple velocities. The large majority of neurons showed modulated responses to these stimuli and responded most strongly at low ripple densities and velocities. The period histograms of their responses were subjected to Fourier analysis, and the ratio of the magnitudes of the f ₁ and f ₀ (DC) components of these responses were calculated to give a quantitative index of response linearity. For 82 out of 396 neurons tested (20.7%) this ratio remained above 1.0 over the entire range of ripple densities and velocities. These neurons were classified as 'consistently linear'. A further 134/396 (33.8%) of neurons maintained an f ₁/ f ₀ ratio above 1.0 for either a range of ripple densities at a fixed ripple velocity, or over a range of ripple velocities at a specific ripple density, and were classified as 'locally linear'. Interestingly, for the superficial layers of the primary auditory cortex, consistently linear and locally linear neurons outnumbered nonlinear neurons by a 2:1 ratio. The converse was true for the deep layers. Unlike in primary visual cortex, where f ₁/ f ₀ ratios have been reported to exhibit a bimodal distribution with a minimum at   f ₁/ f ₀≈ 1  , f ₁/ f ₀ ratios for A1 are unimodally distributed with a peak at   f ₁/ f ₀≈ 1  .     

The molecular basis and biological significance of VH replacement

Summary:  First observed in mouse pre-B-cell lines and then in knock-in mice carrying self-reactive IgH transgenes, V _H replacement has now been shown to contribute to the primary B-cell repertoire in humans. Through recombination-activating gene (RAG)-mediated recombination between a cryptic recombination signal sequence (RSS) present in almost all V _H genes and the flanking 23 base pair RSS of an upstream V _H gene, V _H replacement renews the entire V _H -coding region, while leaving behind a short stretch of nucleotides as a V _H replacement footprint. In addition to extending the CDR3 region, the V _H replacement footprints preferentially contribute charged amino acids. V _H replacement rearrangement in immature B cells may either eliminate a self-reactive B-cell receptor or contribute to the generation of self-reactive antibodies. V _H replacement may also rescue non-productive or dysfunctional V _H DJ _H rearrangement in pro-B and pre-B cells. Conversely, V _H replacement of a productive immunoglobulin H gene may generate non-productive V _H replacement to disrupt or temporarily reverse the B-cell differentiation process. V _H replacement can thus play a complex role in the generation of the primary B-cell repertoire.     

Temperature change does not affect force between regulated actin filaments and heavy meromyosin in single-molecule experiments

The temperature dependence of sliding velocity, force and the number of cross-bridges was studied on regulated actin filaments (reconstituted thin filaments) when they were placed on heavy meromyosin (HMM) attached to a glass surface. The regulated actin filaments were used because our previous study on muscle fibres demonstrated that the temperature effect was much reduced in the absence of regulatory proteins. A fluorescently labelled thin filament was attached to the gelsolin-coated surface of a polystyrene bead. The bead was trapped by optical tweezers, and HMM–thin filament interaction was performed at 20–35°C to study the temperature dependence of force at the single-molecule level. Our experiments showed that there was a small increase in force with temperature  ( Q ₁₀= 1.43)  and sliding velocity  ( Q ₁₀= 1.46)  . The small increase in force was correlated with the small increase in the number of cross-bridges  ( Q ₁₀= 1.49)  , and when force was divided by the number of cross-bridges, the result did not depend on the temperature  ( Q ₁₀= 1.03)  . These results demonstrate that the force each cross-bridge generates is fixed and independent of temperature. Our additional experiments demonstrate that tropomyosin (Tm) in the presence of troponin (Tn) and Ca²⁺ enhances both force and velocity, and a truncated mutant, Δ23Tm, diminishes force and velocity. These results are consistent with the hypothesis that Tm in the presence of Tn and Ca²⁺ exerts a positive allosteric effect on actin to make actomyosin linkage more secure so that larger forces can be generated.     

A correlogram analysis of the activity in the rostral ventromedial medulla of awake rats and in rats anesthetized with ketamine or pentobarbital following the administration of morphine

The present study was designed to determine the relative contribution of the gastrocnemius muscle to isometric plantar flexor torque production at varying knee angles, while investigating the activation of the gastrocnemius muscle at standardised non-optimal lengths. Voluntary plantar flexor torque, supramaximally stimulated twitch torque and myoelectric activity (EMG) from the triceps surae were measured at different knee angles. Surface and intra-muscular EMG were recorded from the soleus muscle and the medial and lateral heads of the gastrocnemius muscle in 10 male subjects. With the ankle angle held constant, knee angle was changed in steps of 30° ranging from 180° (extended) to 60° (extreme flexion), while voluntary torque from a 5-s contraction was determined at 10 different levels of voluntary effort, ranging from 10% of maximal effort to maximal effort. To assess effort, supramaximal twitches were superimposed on all voluntary contractions, and additionally during rest. Maximal plantar flexor torque and resting twitch torque decreased significantly in a sigmoidal fashion with increasing knee flexion to 60% of the maximum torque at 180° knee angle. For similar levels of voluntary effort, the EMG root mean square (RMS) of gastrocnemius was less with increased knee flexion, whereas soleus RMS remained unchanged. From these data, it is concluded that the contribution of gastrocnemius to plantar flexor torque is at least 40% of the total torque in the straight leg position. The decrease of gastrocnemius EMG RMS with decreasing muscle length may be brought about by a decrease in the number of fibres within the EMG electrode recording volume and/or impaired neuromuscular transmission.     

The influence of inspiratory muscle work history and specific inspiratory muscle training upon human limb muscle fatigue

The purpose of this study was to assess the influence of the work history of the inspiratory muscles upon the fatigue characteristics of the plantar flexors (PF). We hypothesized that under conditions where the inspiratory muscle metaboreflex has been elicited, PF fatigue would be hastened due to peripheral vasoconstriction. Eight volunteers undertook seven test conditions, two of which followed 4 week of inspiratory muscle training (IMT). The inspiratory metaboreflex was induced by inspiring against a calibrated flow resistor. We measured torque and EMG during isometric PF exercise at 85% of maximal voluntary contraction (MVC) torque. Supramaximal twitches were superimposed upon MVC efforts at 1 min intervals (MVC_TI); twitch interpolation assessed the level of central activation. PF was terminated ( T _lim) when MVC_TI was <50% of baseline MVC. PF T _lim was significantly shorter than control (9.93 ± 1.95 min) in the presence of a leg cuff inflated to 140 mmHg (4.89 ± 1.78 min; P = 0.006), as well as when PF was preceded immediately by fatiguing inspiratory muscle work (6.28 ± 2.24 min; P = 0.009). Resting the inspiratory muscles for 30 min restored the PF T _lim to control. After 4 weeks, IMT, inspiratory muscle work at the same absolute intensity did not influence PF T _lim, but T _lim was significantly shorter at the same relative intensity. The data are the first to provide evidence that the inspiratory muscle metaboreflex accelerates the rate of calf fatigue during PF, and that IMT attenuates this effect.     

Molecular mapping of a site for Cd2+-induced modification of human ether-à-go-go-related gene (hERG) channel activation

Cd²⁺ slows the rate of activation, accelerates the rate of deactivation and shifts the half-points of voltage-dependent activation ( V _0.5,act) and inactivation ( V _0.5,inact) of human ether-à-go-go -related gene (hERG) K⁺ channels. To identify specific Cd²⁺-binding sites on the hERG channel, we mutated potential Cd²⁺-coordination residues located in the transmembrane domains or extracellular loops linking these domains, including five Cys, three His, nine Asp and eight Glu residues. Each residue was individually substituted with Ala and the resulting mutant channels heterologously expressed in Xenopus oocytes and their biophysical properties determined with standard two-microelectrode voltage-clamp technique. Cd²⁺ at 0.5 m m caused a +36 mV shift of V _0.5,act and a +18 mV shift of V _0.5,inact in wild-type channels. Most mutant channels had a similar sensitivity to 0.5 m m Cd²⁺. Mutation of single Asp residues located in the S2 (D456, D460) or S3 (D509) domains reduced the Cd²⁺-induced shift in V _0.5,act, but not V _0.5,inact. Combined mutations of two or three of these key Asp residues nearly eliminated the shift induced by 0.5 m m Cd²⁺. Mutation of D456, D460 and D509 also reduced the comparatively low-affinity effects of Ca²⁺ and Mg²⁺ on V _0.5,act. Extracellular Cd²⁺ modulates hERG channel activation by binding to a coordination site formed, at least in part, by three Asp residues.     

A-Type potassium currents active at subthreshold potentials in mouse cerebellar purkinje cells

Voltage-dependent and calcium-independent K⁺ currents were whole-cell recorded from cerebellar Purkinje cells in slices. Tetraethylammonium (TEA, 4 m m ) application isolated an A-type K⁺ current ( I _{k ( a )}) with a peak amplitude, at +20 mV, of about one third of the total voltage-dependent and calcium-independent K⁺ current. The I _{k ( a )} activated at about −60 mV, had a V _0.5 of activation of −24.9 mV and a V _0.5 of inactivation of −69.2 mV. The deactivation time constant at −70 mV was 3.4 ± 0.4 ms, while the activation time constant at +20 mV was 0.9 ± 0.2 ms. The inactivation kinetics was weakly voltage dependent, with two time constants; those at +20 mV were 19.3 ± 3.1 and 97.6 ± 9.8 ms. The recovery from inactivation had two time constants of 60.8 ms (78.4%) and 962.3 ms (21.6%). The I _{k ( a )} was blocked by 4-aminopyridine with an IC₅₀ of 67.6 μM. Agitoxin-2 (2 n m ) blocked 17.4 ± 2.1% of the I _{k ( a )}. Flecainide completely blocked the I _{k ( a )} with a biphasic effect with IC₅₀ values of 4.4 and 183.2 μM. In current-clamp recordings the duration of evoked action potentials was affected neither by agitoxin-2 (2 n m ) nor by flecainide (3 μM), but action potentials that were already broadened by TEA were further prolonged by 4-aminopyridine (100 μM). The amplitude of the hyperpolarisation at the end of depolarising steps was reduced by all these blockers.     

Differences in sodium voltage-gated channel properties according to myosin heavy chain isoform expression in single muscle fibres

The myosin heavy chain (MHC) isoform determines the characteristics and shortening velocity of muscle fibres. The functional properties of the muscle fibre are also conditioned by its membrane excitability through the electrophysiological properties of sodium voltage-gated channels. Macropatch-clamp is used to study sodium channels in fibres from peroneus longus (PL) and soleus (Sol) muscles (Wistar rats, n = 8). After patch-clamp recordings, single fibres are identified by SDS-PAGE electrophoresis according to their myosin heavy chain isoform (slow type I and the three fast types IIa, IIx, IIb). Characteristics of sodium currents are compared (Student's t test) between fibres exhibiting only one MHC isoform. Four MHC isoforms are identified in PL and only type I in Sol single fibres. In PL, maximal sodium current ( I _max), maximal sodium conductance ( g _Na,max) and time constants of activation and inactivation (τ _m and τ _h ) increase according to the scheme I→IIa→IIx→IIb ( P < 0.05). τ _m values related to sodium channel type and/or function, are similar in Sol I and PL IIb fibres ( P = 0.97) despite different contractile properties. The voltage dependence of activation ( V _a,1/2) shows a shift towards positive potentials from Sol type I to IIa, IIx and finally IIb fibres from PL ( P < 0.05). These data are consistent with the earlier recruitment of slow fibres in a fast-mixed muscle like PL, while slow fibres of postural muscle such as soleus could be recruited in the same ways as IIb fibres in a fast muscle.     

Tidal volume, cardiac output and functional residual capacity determine end-tidal CO2 transient during standing up in humans

In man assuming the upright position, end-tidal P _CO2 ( P _ETCO2 ) decreases. With the rising interest in cerebral autoregulation during posture change, which is known to be affected by P _ETCO2 , we sought to determine the factors leading to hypocapnia during standing up from the supine position. To study the contribution of an increase in tidal volume ( V _T ) and breathing frequency, a decrease in stroke volume (SV), a ventilation–perfusion ( V/Q ) gradient and an increase in functional residual capacity (FRC) to hypocapnia in the standing position, we developed a mathematical model of the lung to follow breath-to-breath variations in P _ETCO2 . A gravity-induced apical-to-basal V/Q gradient in the lung was modelled using nine lung segments. We tested the model using an eight-subject data set with measurements of V _T , pulmonary O₂ uptake and breath-to-breath lumped SV. On average, the P _ETCO2 decreased from 40 mmHg to 36 mmHg after 150 s standing. Results show that the model is able to track breath-to-breath P _ETCO2 variations ( r ²= 0.74, P < 0.05). Model parameter sensitivity analysis demonstrates that the decrease in P _ETCO2 during standing is due primarily to increased V _T , and transiently to decreased SV and increased FRC; a slight gravity-induced V/Q mismatch also contributes to the hypocapnia. The influence of cardiac output on hypocapnia in the standing position was verified in experiments on human subjects, where first breathing alone, and then breathing, FRC and V/Q were controlled.     

Modulatory effects of low- and high-frequency repetitive transcranial magnetic stimulation on visual cortex of healthy subjects undergoing light deprivation

The aim of the present study was to explore further the effects of light deprivation (LD) on visual cortex excitability. Healthy subjects reporting reliable induction of phosphenes by occipital transcranial magnetic stimulation (TMS) underwent 60 min of complete LD. Phosphene threshold (PT) was measured before ( T ₀), after 45 min ( T ₁) and 60 min ( T ₂) of LD, and then every 10 min after light re-exposure until recovery to T ₀ values. Repetitive TMS (rTMS) (at 1 or 10 Hz) was applied in separate sessions during the last 15 min of LD. PTs significantly decreased after 45 min of LD. rTMS differentially modified the effects of 60 min LD on PTs depending on stimulation frequency. One hertz rTMS did not change the decreasing of PT values as observed in baseline condition, but significantly prolonged the time to recover T ₀ PT values after light re-exposure. By contrast, 10 Hz rTMS significantly increased PT and the time to recover T ₀ PT values after light re-exposure was shortened. The results of this study show that the modulatory effects of different rTMS frequencies on visual cortex critically depend on the pre-existing excitability state of inhibitory and facilitatory circuits, and provide novel insights into the neurophysiological changes that take place in the visual cortex following functional visual deafferentation.     

IgE responses to Dermatophagoides pteronyssinus native major allergens Der p 1 and Der p 2 during long-term specific immunotherapy

We investigated by ELISA the IgE response to whole extract of the house-dust mite Dermatophagoides pteronyssinus (Dp) and to the native major allergens, Der p 1 and Der p 2, in sera from 18 adult patients (group A) with Dp-allergic asthma before ( t ₀) and 1, 2, 3, and 4 ( t ₁– t ₄) years after subcutaneous specific immunotherapy (SIT). A qualitative reduction ( P =0.05) of the IgE responses to Dp and Der p 2 was observed from t ₁ to t ₄, but a highly statistical significant decrease appeared at t ₃, ( P < 0.01). With regard to Der p 1 IgE values, the immunotherapy induced a significant decrease ( P < 0.01) at t ₃, but not before. In group A, the IgE responses to Der p 1 and Der p 2 were not correlated at t ₀ ( r _s=0.31; P = 0.2l) but were correlated at t₃ ( r _s= 0.78; P=0.001). We also examined sera from 14 adult patients (group B, same SIT schedule as group A) who were without respiratory symptoms at the end of the third year (t₃) of Dp SIT. At this time ( t ₃), there were no significant differences in Der p 1 and Der p 2 IgE levels between group A and group B.     

Time and frequency domain analysis of electromyogram and sound myogram in the elderly

The aim of this work was to evaluate the influence of the ageing process on the time and frequency domain properties of the surface electrical and mechanical activity of muscle. In 20 healthy elderly subjects (10 men and 10 women, age range 65–78 years) and in 20 young controls, during isometric contractions of the elbow flexors in the 20%–100% range of the maximal voluntary contraction (MVC), estimations were made of the root mean square (rms) and the mean frequency (MF) of the power density spectrum distribution, from the surface electromyogram (EMG) and sound myogram (0SMG) signals, detected at the belly of the biceps brachii muscle. Compared to the young controls, the MVC was lower in the elderly subjects (P < 0.05); at the same %MVC the rms and the MF of EMG and SMG were lower (P < 0.05) in elderly subjects; the rms and MF of the two signals increased as a function of the effort level in all groups. Only in the 80%–100% MVC range did the EMG-MF level off and the SMG-rms decrease; in contrast the young controls, at 80% MVC the high frequency peak in the SMG power spectrum density distribution was not present in the elderly subjects. The results for MVC and %MVC can be related to the reduction in the numbers of muscle fibres in aged subjects. In particular, the lack of fast twitch fibre motor units (MU), attaining high firing rates, might also explain the result at 80% MVC. In 80%–100% MVC range the two signals rms and MF behaviour may have been related to the end of the recruitment of larger MU with high conduction velocity, and to the further increment of MU firing rate in the biceps brachii muscle beyond 80% MVC, respectively. Thus, the coupled analysis of the EMG and SMG with force suggests that in the elderly subjects the reduction of the number of muscle fibres may have co-existed with a MU activation pattern similar to that of the young subjects.     

The surface mechanomyogram as a tool to describe the influence of fatigue on biceps brachii motor unit activation strategy. Historical basis and novel evidence

The surface mechanomyogram (MMG) (detectable at the muscle surface as MMG by accelerometers, piezoelectric contact sensors or other transducers) is the summation of the activity of single motor units (MUs). Each MU contribution is related to the pressure waves generated by the active muscle fibres. The first part of this article will review briefly the results obtained by our group studying the possible role of motor unit recruitment and firing rate in determining the characteristics of the MMG during stimulated and voluntary contractions. The second part of this article will study the MMG and EMG during a short isometric force ramp from 0 to 90% of the maximal voluntary contraction (MVC) in fresh and fatigued biceps brachii. The aim is to verify whether changes in motor unit activation strategy in voluntarily fatigued muscle could be specifically reflected in the time and frequency domain parameters of the MMG. MMG-RMS vs. %MVC: at fatigue the MMG-RMS did not present the well known increment, when effort level increases, followed by a clear decrement at near-maximal contraction levels. MMG-MF vs. %MVC: compared to fresh muscle the fatigued biceps brachii showed an MF trend significantly shifted towards lower values and the steeper MF increment, from 65 to 85% MVC, was not present. The alteration in the MMG and EMG parameters vs. %MVC relationships at fatigue seems to be related to the impossibility of recruiting fast, but more fatigable MUs, and to the lowering of the global MUs firing during the short isometric force ramp investigated.     

The influence of muscle length on the fatigue-related reduction in joint range of motion of the human dorsiflexors

The fatigue-related reduction in joint range of motion (ROM) during dynamic contraction tasks may be related to muscle length-dependent alterations in torque and contractile kinetics, but this has not been systematically explored previously. Twelve young men performed a repetitive voluntary muscle shortening contraction task of the dorsiflexors at a contraction load of 30% of maximum voluntary isometric contraction (MVC) torque, until total 40° ROM had decreased by 50% at task failure (POST) to 20° ROM. At both a short (5° dorsiflexion) and long muscle length (35° plantar flexion joint angle relative to a 0° neutral ankle joint position), voluntary activation, MVC torque, and evoked tibialis anterior contractile properties of a 52.8 Hz high-frequency isometric tetanus [peak evoked torque, maximum rate of torque development (MRTD), maximum rate of relaxation (MRR)] were evaluated at baseline (PRE), at POST, and up to 10 min of recovery. At POST, we measured similar fatigue-related reductions in torque (voluntary and evoked) and slowing of contractile kinetics (MRTD and MRR) at both the short and long muscle lengths. Thus, the fatigue-related reduction in ROM could not be explained by length-dependent fatigue. Although torque (voluntary and evoked) at both muscle lengths was depressed and remained blunted throughout the recovery period, this was not related to the rapid recovery of ROM at 0.5 min after task failure. The reduction in ROM, however, was strongly related to the reduction in joint angular velocity (R ²  = 0.80) during the fatiguing task, although additional factors cannot yet be overlooked.