scholarly journals Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy

Neurology ◽  
2020 ◽  
Vol 94 (11) ◽  
pp. e1157-e1170 ◽  
Author(s):  
Saskia Lassche ◽  
Nicol C. Voermans ◽  
Robbert van der Pijl ◽  
Marloes van den Berg ◽  
Arend Heerschap ◽  
...  

ObjectiveTo investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.MethodsWe collected 50 muscle biopsies (26 vastus lateralis, 24 tibialis anterior) from 14 patients with genetically confirmed FSHD and 12 healthy controls. Single muscle fibers (n = 547) were isolated for contractile measurements. Titin content and titin phosphorylation were examined in vastus lateralis muscle biopsies.ResultsSingle muscle fiber specific force was intact at saturating and physiologic calcium concentrations in all FSHD biopsies, with (FSHDFAT) and without (FSHDNORMAL) fatty infiltration, compared to healthy controls. Myofilament calcium sensitivity of force is increased in single muscle fibers obtained from FSHD muscle biopsies with increased fatty infiltration, but not in FSHD muscle biopsies without fatty infiltration (pCa50: 5.77–5.80 in healthy controls, 5.74–5.83 in FSHDNORMAL, and 5.86–5.90 in FSHDFAT single muscle fibers). Cross-bridge cycling kinetics at saturating calcium concentrations and myofilament cooperativity did not differ from healthy controls. Development of single muscle fiber passive tension was changed in all FSHD vastus lateralis and in FSHDFAT tibialis anterior, resulting in increased fiber stiffness. Titin content was increased in FSHD vastus lateralis biopsies; however, titin phosphorylation did not differ from healthy controls.ConclusionMuscle weakness in patients with FSHD is not caused by reduced specific force of individual muscle fibers, even in severely affected tissue with marked fatty infiltration of muscle tissue.

2011 ◽  
Vol 26 (3) ◽  
pp. 1077-1085 ◽  
Author(s):  
Rizwan Qaisar ◽  
Guillaume Renaud ◽  
Kevin Morine ◽  
Elisabeth R. Barton ◽  
H. Lee Sweeney ◽  
...  

2000 ◽  
Vol 89 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Scott Trappe ◽  
David Williamson ◽  
Michael Godard ◽  
David Porter ◽  
Greg Rowden ◽  
...  

The purpose of this study was to examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older men ( n = 7; age = 74 ± 2 yr and weight = 75 ± 5 kg). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsy samples were obtained from the vastus lateralis before and after PRT (pre- and post-PRT, respectively). For analysis, chemically skinned single muscle fibers were studied at 15°C for peak tension [the maximal isometric force (Po)], unloaded shortening velocity ( V o), and force-velocity parameters. In this study, a total of 199 (89 pre- and 110 post-PRT) myosin heavy chain (MHC) I and 99 (55 pre- and 44 post-PRT) MHC IIa fibers were reported. Because of the minimal number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 20% (83 ± 1 to 100 ± 1 μm) and 13% (86 ± 1 to 97 ± 2 μm) in MHC I and IIa fibers, respectively ( P < 0.05). Po was higher ( P < 0.05) in MHC I (0.58 ± 0.02 to 0.90 ± 0.02 mN) and IIa (0.68 ± 0.02 to 0.85 ± 0.03 mN) fibers. Muscle fiber V o was elevated 75% (MHC I) and 45% (MHC IIa) after PRT ( P < 0.05). MHC I and IIa fiber power increased ( P < 0.05) from 7.7 ± 0.5 to 17.6 ± 0.9 μN · fiber lengths · s−1 and from 25.5 to 41.1 μN · fiber lengths · s−1, respectively. These data indicate that PRT in elderly men increases muscle cell size, strength, contractile velocity, and power in both slow- and fast-twitch muscle fibers. However, it appears that these changes are more pronounced in the MHC I muscle fibers.


2001 ◽  
Vol 91 (5) ◽  
pp. 1955-1961 ◽  
Author(s):  
D. L. Williamson ◽  
P. M. Gallagher ◽  
C. C. Carroll ◽  
U. Raue ◽  
S. W. Trappe

The purpose of this investigation was to examine the effects of 12 wk of progressive resistance training (PRT) on single muscle fiber myosin heavy chain (MHC; I, I/IIa, I/IIa/IIx, IIa, IIa/IIx, IIx) isoform proportions in young individuals. Young, untrained men (YM; n = 6) and women (YW; n = 6) (age = 22 ± 1 and 25 ± 2 yr for YW and YM, respectively) received pre- and post-PRT muscle biopsies from the right vastus lateralis for single muscle fiber MHC distribution by electrophoretic analysis (192 ± 5 pre- and 183 ± 6 post-fibers/subject analyzed; 4,495 fibers total). Data are presented as percentages of the total fibers analyzed per subject. The PRT protocol elicited an increase in the pure MHC IIa (Δ = + 24 and + 27; YW and YM, respectively; P < 0.05) with no change in the pure MHC I distribution. The hybrid MHC distributions decreased I/IIa/IIx (Δ = −2; YM and YW; P < 0.05), IIa/IIx (Δ = −13 and −19 for YM and YW, respectively; P < 0.05), and total hybrid fiber proportion (I/IIa + I/IIa/IIx + IIa/IIx) decreased (Δ = −19 and −30 for YM and YW, respectively; P < 0.05) with the training, as did the MHC IIx distribution (Δ = −2; YW only; P < 0.05). Alterations in the predominance of MHC isoforms within hybrid fibers (decrease in MHC I-dominant I/IIa and nondominant MHC IIa/IIx, increase in MHC IIa-dominant IIa/IIx; P < 0.05) appeared to contribute to the increase in the MHC IIa proportion. Electrophoresis of muscle cross sections revealed an ∼7% increase ( P< 0.05) in MHC IIa proportion in both groups, whereas the MHC IIx decrease by 7.5 and 11.6% post-PRT in YW and YM, respectively. MHC I proportions increase in YM by 4.8% ( P < 0.05) post-PRT. These findings further support previous resistance training data in young adults with respect to the increase in the MHC IIa proportions but demonstrate that a majority of the change can be attributed to the decrease in single-fiber hybrid proportions.


1970 ◽  
Vol 55 (2) ◽  
pp. 243-253 ◽  
Author(s):  
B. A. Curtis

An apparatus is described which collects the effluent from the center 0.7 cm of a single muscle fiber or bundle of muscle fibers. It was used to study the efflux of 45Ca from twitch muscle fibers. The efflux can be described by three time constants 18 ± 2 min, 300 ± 40 min, and 882 ± 172 min. These kinetics have been interpreted as those of a three-compartment system. The fastest is thought to be on the surface membrane of the muscle and of the T system. It contains 0.07 ± 0.03 mM Ca/liter of fiber and the Ca efflux is 0.11 ± 0.04 pM Ca/cm2. sec. The intermediate rate compartment is thought to represent the Ca in the longitudinal reticulum. It contains approximately 0.77 mM Ca/liter. Only the efflux from this compartment increases during stimulation. The most slowly exchanging compartment is poorly defined. Neither Ca-free nor Ni-Ringer solutions alter the rate of loss from the fastest exchanging compartment. Ni apparently alters the rate of loss from the slowest compartment.


2016 ◽  
Vol 310 (4) ◽  
pp. C318-C327 ◽  
Author(s):  
Geoffrey A. Power ◽  
Fábio C. Minozzo ◽  
Sally Spendiff ◽  
Marie-Eve Filion ◽  
Yana Konokhova ◽  
...  

Normal adult aging is associated with impaired muscle contractile function; however, to what extent cross-bridge kinetics are altered in aging muscle is not clear. We used a slacken restretch maneuver on single muscle fiber segments biopsied from the vastus lateralis of young adults (∼23 yr), older nonathlete (NA) adults (∼80 yr), and age-matched world class masters athletes (MA; ∼80 yr) to assess the rate of force redevelopment ( ktr) and cross-bridge kinetics. A post hoc analysis was performed, and only the mechanical properties of “slow type” fibers based on unloaded shortening velocity ( Vo) measurements are reported. The MA and NA were ∼54 and 43% weaker, respectively, for specific force compared with young. Similarly, when force was normalized to cross-sectional area determined via the fiber shape angularity data, both old groups did not differ, and the MA and NA were ∼43 and 48% weaker, respectively, compared with young ( P < 0.05). Vo for both MA and NA old groups was 62 and 46% slower, respectively, compared with young. Both MA and NA adults had approximately two times slower values for ktr compared with young. The slower Vo in both old groups relative to young, coupled with a similarly reduced ktr, suggests impaired cross-bridge kinetics are responsible for impaired single fiber contractile properties with aging. These results challenge the widely accepted resilience of slow type fibers to cellular aging.


2020 ◽  
Vol 142 (8) ◽  
Author(s):  
Alex M. Noonan ◽  
Derek P. Zwambag ◽  
Nicole Mazara ◽  
Erin Weersink ◽  
Geoffrey A. Power ◽  
...  

Abstract Studies on single muscle fiber passive material properties often report relatively large variation in elastic modulus (or normalized stiffness), and it is not clear where this variation arises. This study was designed to determine if the stiffness, normalized to both fiber cross-sectional area and length, is inherently different between types 1 and 2 muscle fibers. Vastus lateralis fibers (n = 93), from ten young men, were mechanically tested using a cumulative stretch-relaxation protocol. SDS-PAGE classified fibers as types 1 or 2. While there was a difference in normalized stiffness between fiber types (p = 0.0019), an unexpected inverse relationship was found between fiber diameter and normalized stiffness (r = −0.64; p &lt; 0.001). As fiber type and diameter are not independent, a one-way analysis of covariance (ANCOVA) including fiber diameter as a covariate was run; this eliminated the effect of fiber type on normalized stiffness (p = 0.1935). To further explore the relationship between fiber size and elastic properties, we tested whether stiffness was linearly related to fiber cross-sectional area, as would be expected for a homogenous material. Passive stiffness was not linearly related to fiber area (p &lt; 0.001), which can occur if single muscle fibers are better represented as composite materials. The rule of mixtures for composite materials was used to explore whether the presence of a stiff perimeter-based fiber component could explain the observed results. The model (R2 = 0.38) predicted a perimeter-based normalized stiffness of 8800 ± 2600 kPa/μm, which is within the range of basement membrane moduli reported in the literature.


2016 ◽  
Vol 121 (4) ◽  
pp. 878-884 ◽  
Author(s):  
Greg J. Grosicki ◽  
Robert A. Standley ◽  
Kevin A. Murach ◽  
Ulrika Raue ◽  
Kiril Minchev ◽  
...  

We examined single muscle fiber contractile function of the oldest-old (3F/2M, 89 ± 1 yr old) enrolled in The Health, Aging, and Body Composition Study (The Health ABC Study). Vastus lateralis muscle biopsies were obtained and single muscle fiber function was determined ( n = 105) prior to myosin heavy chain (MHC) isoform identification with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cross-sectional area of MHC I muscle fibers (5,576 ± 333 μm2; n = 58) was 21% larger ( P < 0.05) than MHC IIa fibers (4,518 ± 386 μm2; n = 47). Normalized power (an indicator of muscle fiber quality incorporating size, strength, and speed) of MHC I and IIa muscle fibers was 2.3 ± 0.1 and 17.4 ± 0.8 W/l, respectively. Compared with previous research from our lab using identical procedures, MHC I normalized power was 28% higher than healthy 20 yr olds and similar to younger octogenarians (∼80 yr old). Normalized power of MHC IIa fibers was 63% greater than 20 yr olds and 39% greater than younger octogenarians. These comparative data suggest that power output per unit size (i.e., muscle quality) of remaining muscle fibers improves with age, a phenomenon more pronounced in MHC IIa fibers. Age-related single muscle fiber quality improvements may be a compensatory mechanism to help offset decrements in whole muscle function.


2011 ◽  
Vol 43 (24) ◽  
pp. 1334-1350 ◽  
Author(s):  
Sudhakar Aare ◽  
Julien Ochala ◽  
Holly S. Norman ◽  
Peter Radell ◽  
Lars I. Eriksson ◽  
...  

Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.


2020 ◽  
Vol 7 (4) ◽  
pp. 495-504
Author(s):  
Saskia Lassche ◽  
Benno Küsters ◽  
Arend Heerschap ◽  
Maxime V.P. Schyns ◽  
Coen A.C. Ottenheijm ◽  
...  

Background: Muscle MRI is increasingly used as a diagnostic and research tool in muscle disorders. However, the correlation between MRI abnormalities and histopathological severity is largely unknown. Objective: To investigate correlations between muscle MRI abnormalities and histopathological severity in healthy controls and patients with muscle disease. Methods: We performed quantitative MRI and histopathological analysis in 35 patients with inclusion body myositis, facioscapulohumeral muscular dystrophy or oculopharyngeal muscular dystrophy and 12 healthy controls. Participants contributed needle biopsies of the vastus lateralis and/or tibialis anterior, yielding 77 muscle biopsies with matched T1, T2 and TIRM MRI imaging. Muscle biopsies were evaluated with a semi-quantitative histopathology severity grading scale (range 0–12) and an inflammation severity grading scale (range 0–3). Results: In muscle disease, histopathology sum scores ranged from 0 to 11 and correlated significantly with fat percentage as measured on MRI (Spearman’s rho = 0.594, p < 0.001). Muscle edema on muscle MRI was associated with increased amounts of inflammation (p < 0.001). Mild abnormalities occured in 95% of control biopsies and were more pronounced in tibialis anterior (median sum score of 1±1 in vastus lateralis and 2±1 in tibialis anterior (p = 0.048)). Conclusion: In muscle disease, fatty infiltration on MRI correlates moderately with muscle histopathology. Histopathological abnormalities can occur prior to the onset of fatty infiltration. In middle-aged controls, almost all biopsies showed some histopathological abnormalities. The findings from this study may facilitate the choice for appropriate imaging sequences as outcome measures in therapeutic trials.


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