scholarly journals Intrinsic contractile dysfunction in a surgical model of muscle hypertrophy

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Nao Tokuda ◽  
Daiki Watanabe ◽  
Yuki Ashida ◽  
Iori Kimura ◽  
Azuma Naito ◽  
...  
Keyword(s):  
Muscle Hypertrophy ◽  
Isometric Force ◽  
Force Production ◽  
Compensatory Hypertrophy ◽  
Skinned Fibers ◽  
Contractile Dysfunction ◽  
Specific Force ◽  
Surgical Ablation ◽  
Cross Sectional ◽  
Domain 3

Synergistic ablation (SA) is widely used to induce muscle hypertrophy in rodent studies. However, it has been demonstrated that SA-induced compensatory hypertrophy induces increases in maximum isometric force that are smaller in magnitude than the increase in muscle cross-sectional area, suggesting a reduction in the specific force production due to intrinsic contractile dysfunction in the hypertrophied fibers. Here, by using the mechanical skinned fibers, we investigated the mechanisms behind the reduction in specific force in the compensatory hypertrophied muscles. Rats had unilateral surgical ablation of the gastrocnemius and soleus muscles to induce the compensatory hypertrophy in the plantaris muscles. Two wk after surgery, the mean fiber diameter was increased by 19% in the SA group compared with the contralateral control (CNT) group. In contrast, compared with the CNT group, both the depolarization-induced force (−51%) and the Ca2+-activated maximum specific force (−32%) were markedly reduced in skinned fibers from the SA group. These deleterious functional alterations were accompanied by decreases in the amount of DHPRα1, RYR, junctophilin 1, and SH3 and cysteine-rich domain 3 (STAC3) in SA muscles. Thus, these data clearly show that SA induces not only an increase in skeletal muscle fiber hypertrophy but also leads to a reduction in the intrinsic contractile dysfunction due to the excitation–contraction uncoupling and impaired force-generating capacity.

The α7β1-integrin accelerates fiber hypertrophy and myogenesis following a single bout of eccentric exercise

2011 ◽  
Vol 301 (4) ◽  
pp. C938-C946 ◽  
Author(s):  
Tara N. Lueders ◽  
Kai Zou ◽  
Heather D. Huntsman ◽  
Benjamin Meador ◽  
Ziad Mahmassani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Eccentric Exercise ◽  
Time Course ◽  
Muscle Hypertrophy ◽  
Isometric Force ◽  
Transmembrane Protein ◽  
Mechanical Strain ◽  
Cellular Growth ◽  
Cross Sectional ◽  
Single Bout

The α7β1-integrin is a heterodimeric transmembrane protein that adheres to laminin in the extracellular matrix, representing a critical link that maintains structure in skeletal muscle. In addition to preventing exercise-induced skeletal muscle injury, the α7-integrin has been proposed to act as an intrinsic mechanosensor, initiating cellular growth in response to mechanical strain. The purpose of this study was to determine the extent to which the α7-integrin regulates muscle hypertrophy following eccentric exercise. Wild-type (WT) and α7-integrin transgenic (α7Tg) mice completed a single bout of downhill running exercise (−20°, 17 m/min, 60 min), and gastrocnemius-soleus complexes were collected 1, 2, 4, and 7 days (D) postexercise (PE). Maximal isometric force was maintained and macrophage accumulation was suppressed in α7Tg muscle 1D PE. Mean fiber cross-sectional area was unaltered in WT mice but increased 40% in α7Tg mice 7D PE. In addition, a rapid and striking fivefold increase in embryonic myosin heavy chain-positive fibers appeared in α7Tg mice 2D PE. Although Pax7-positive satellite cells were increased in α7Tg muscle 1D PE, the number of nuclei per myofiber was not altered 7D PE. Phosphorylation of mammalian target of rapamycin (mTOR) was significantly elevated in α7Tg 1D PE. This study provides the first demonstration that the presence of the α7β1-integrin in skeletal muscle increases fiber hypertrophy and new fiber synthesis in the early time course following a single bout of eccentric exercise. Further studies are necessary to elucidate the precise mechanism by which the α7-integrin can enhance muscle hypertrophy following exercise.

scholarly journals Decreased specific force and power production of muscle fibers from myostatin-deficient mice are associated with a suppression of protein degradation

2011 ◽  
Vol 111 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Christopher L. Mendias ◽  
Erdan Kayupov ◽  
Joshua R. Bradley ◽  
Susan V. Brooks ◽  
Dennis R. Claflin
Keyword(s):  
Myosin Heavy Chain ◽  
Muscle Mass ◽  
Heavy Chain ◽  
Extensor Digitorum Longus ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Force Production ◽  
Sectional Area ◽  
Cross Sectional ◽  
Maximum Isometric Force

Myostatin ( MSTN) is a member of the transforming growth factor-β superfamily of cytokines and is a negative regulator of skeletal muscle mass. Compared with MSTN+/+ mice, the extensor digitorum longus muscles of MSTN−/− mice exhibit hypertrophy, hyperplasia, and greater maximum isometric force production (Fo), but decreased specific maximum isometric force (sFo; Fo normalized by muscle cross-sectional area). The reason for the reduction in sFo was not known. Studies in myotubes indicate that inhibiting myostatin may increase muscle mass by decreasing the expression of the E3 ubiquitin ligase atrogin-1, which could impact the force-generating capacity and size of muscle fibers. To gain a greater understanding of the influence of myostatin on muscle contractility, we determined the impact of myostatin deficiency on the contractility of permeabilized muscle fibers and on the levels of atrogin-1 and ubiquitinated myosin heavy chain in whole muscle. We hypothesized that single fibers from MSTN−/− mice have a greater Fo, but no difference in sFo, and a decrease in atrogin-1 and ubiquitin-tagged myosin heavy chain levels. The results indicated that fibers from MSTN−/− mice have a greater cross-sectional area, but do not have a greater Fo and have a sFo that is significantly lower than fibers from MSTN+/+ mice. The extensor digitorum longus muscles from MSTN−/− mice also have reduced levels of atrogin-1 and ubiquitinated myosin heavy chain. These findings suggest that myostatin inhibition in otherwise healthy muscle increases the size of muscle fibers and decreases atrogin-1 levels, but does not increase the force production of individual muscle fibers.

scholarly journals Behaviour of Motor Units during Submaximal Isometric Contractions in Chronically Strength-Trained individuals

2021 ◽  
Author(s):  
Andrea Casolo ◽  
Alessandro Del Vecchio ◽  
Thomas Grant Balshaw ◽  
Sumiaki Maeo ◽  
Marcel Bahia Lanza ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Biceps Brachii ◽  
Isometric Force ◽  
Force Production ◽  
Motor Units ◽  
Surface Emg ◽  
Muscle Size ◽  
Training Experience ◽  
Cross Sectional ◽  
Neural Input

Neural and morphological adaptations combine to underpin the enhanced muscle strength following prolonged exposure to strength training, although their relative importance remains unclear. We investigated the contribution of motor unit (MU) behaviour and muscle size to submaximal force production in chronically strength-trained athletes (ST) vs. untrained controls (UT). Sixteen ST (age, 22.9±3.5 yr; training experience, 5.9±3.5 yr) and fourteen UT (age, 20.4±2.3 yr) performed maximal voluntary isometric force (MViF) and ramp contractions (at 15, 35, 50, 70%MViF) with elbow flexors, whilst high-density surface EMG (HDsEMG) was recorded from the biceps brachii (BB). Recruitment thresholds (RT) and discharge rates (DR) of MUs identified from the submaximal contractions were assessed. The neural drive-to-muscle gain was estimated from the relation between changes in force (ΔFORCE, i.e. muscle output) relative to changes in MU DR (ΔDR, i.e. neural input). BB maximum anatomical cross-sectional area (ACSAMAX) was also assessed by MRI. MViF (+64.8% vs. UT, P<0.001) and BB ACSAMAX (+71.9%, P<0.001) were higher in ST. Absolute MU RT was higher in ST (+62.6%, P<0.001), but occurred at similar normalized forces. MU DR did not differ between groups at the same normalized forces. The absolute slope of the ΔFORCE-ΔDR relationship was higher in ST (+66.9%, P=0.002), whereas it did not differ for normalized values. We observed similar MU behaviour between ST athletes and UT controls. The greater absolute force-generating capacity of ST for the same neural input, demonstrates that morphological, rather than neural, factors are the predominant mechanism for their enhanced force generation during submaximal efforts.

Force deficit during the onset of muscle hypertrophy

1989 ◽  
Vol 67 (6) ◽  
pp. 2600-2607 ◽  
Author(s):  
S. C. Kandarian ◽  
T. P. White
Keyword(s):  
Muscle Mass ◽  
Protein Concentration ◽  
Muscle Hypertrophy ◽  
Structural Changes ◽  
Relative Magnitude ◽  
Interstitial Space ◽  
Cross Sectional Area ◽  
Specific Force ◽  
Sectional Area ◽  
Cross Sectional

The purpose was to study selected structural changes associated with the deficit in maximum specific force (N/cm2) during the early development of skeletal muscle hypertrophy. Ablation of gastrocnemius and plantaris muscles was performed bilaterally in 35-day-old rats (n = 41), and the soleus muscle was studied from days 1 to 30 thereafter. Compared with control muscles from age-matched unoperated rats (n = 48), muscle mass and cross-sectional area increased in parallel from 28 to 52% over the 30-day postoperative period. Specific force of hypertrophied muscle was depressed 38% at days 1 and 3, and by 28% from days 5 to 30 after synergistic muscle ablation compared with age-matched control values. Interstitial space was 38% greater than the control value of 20.4 +/- 1 microliters/100 mg at day 1 only. Protein concentration was depressed 15% for 7 days after the ablation operation, and connective tissue protein concentration was unchanged. The relative magnitude of increased mean fiber cross-sectional area was less than that of muscle mass until day 7 after ablation. Mononuclear cell infiltration in interfascicular spaces occurred from days 3 to 30 without light microscopic evidence of muscle fiber injury. Initial functional deficits are explained in part by an enlarged interstitial space and decreased protein concentration; later deficits are likely accounted for by intracellular changes.

Mechanical deficit persists during long-term muscle hypertrophy

1990 ◽  
Vol 69 (3) ◽  
pp. 861-867 ◽  
Author(s):  
S. C. Kandarian ◽  
T. P. White
Keyword(s):  
Isometric Force ◽  
Force Production ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Plantaris Muscle ◽  
Cross Sectional ◽  
Control Value ◽  
Muscle Cross Sectional Area ◽  
Synergistic Muscle

Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age-matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production.

scholarly journals Impaired overload-induced hypertrophy in obese Zucker rat slow-twitch skeletal muscle

2010 ◽  
Vol 108 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Satyanarayana Paturi ◽  
Anil K. Gutta ◽  
Sunil K. Kakarla ◽  
Anjaiah Katta ◽  
Eric C. Arnold ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Internal Control ◽  
Muscle Hypertrophy ◽  
Surgical Ablation ◽  
Cross Sectional ◽  
Insulin Resistant ◽  
Muscle Loading ◽  
Wet Weight ◽  
Mechanical Overload

The effect of insulin resistance (IR) on the adaptation of skeletal muscle loading is not well understood. Here we examine whether the soleus muscles of the lean Zucker (LZ) and insulin-resistant obese Zucker (OZ) rat exhibit differences in their ability to undergo muscle hypertrophy following 8 wk of mechanical overload. Four-week-old male LZ ( n = 5) and OZ ( n = 5) rats underwent unilateral surgical ablation of the gastrocnemius muscle while the contralateral hindlimb was used as an internal control. Mechanical overload increased soleus muscle wet weight (LZ 57% and OZ 33%, respectively; P < 0 .05) and average type 1 fiber cross-sectional area (LZ 32% and OZ 5%, respectively; P < 0.05) in LZ and OZ rats, while the magnitude of these increases was greater in the LZ animals ( P < 0 .05). The reduced degree of muscle hypertrophy observed in the OZ animals was associated with decreases in the ability of the OZ soleus muscle to phosphorylate p70s6kThr 389 and mTOR, while phosphorylation of p70s6kThr 389 was increased in the LZ overloaded soleus by 83% ( P < 0 .05). The amount of Tuberin/TSC2 phosphorylation, an inhibitor of mTOR, was unchanged in the LZ soleus after overload while it was increased (68.3%, P < 0.05) in OZ animals. Conversely, AMPK phosphorylation was decreased in the LZ (−22.77%, P < 0 .05) but increased (57%, P < 0 .05) in the OZ soleus with overload. Taken together, these data suggest that IR or other related comorbidities may impair the ability of the soleus to activate mTOR signaling and undergo load-induced muscle hypertrophy.

Recovery of muscle transfers replacing the total plantar flexor muscle group in rats

1998 ◽  
Vol 84 (6) ◽  
pp. 1865-1871 ◽  
Author(s):  
Stephanie W. Miller ◽  
Cheryl A. Hassett ◽  
John A. Faulkner
Keyword(s):  
Isometric Force ◽  
Force Production ◽  
Plantar Flexor ◽  
Flexor Muscle ◽  
Average Force ◽  
Cross Sectional ◽  
Individual Control ◽  
Control Value ◽  
Muscle Transfers ◽  
Synergistic Muscles

In rats, combinations of plantar flexor muscles representing ∼20, 40, 60, and 80% of the mass of the total plantar flexor group were transferred orthotopically in the absence of synergistic muscles and allowed to recover for 120 days. We hypothesized that, compared with their individual control values for structural and functional variables, the transfers would display a hierarchical array of deficits, proportional to their initial mass and, consequently, inversely proportional to the relative load on the transfers. Surprisingly, compared with their individual control values, each muscle transfer displayed deficits of 30–40% in muscle mass, total fiber cross-sectional area, and maximum isometric force, with the exception of the smallest transfer, the plantaris (PLN) muscle, which recovered 100% of its control value for each of these variables. Therefore, except for the PLN transfer, the muscle transfers studied displayed deficits similar in magnitude to those reported for muscles transferred in the presence of synergistic muscles. The greater recovery of the PLN transfer was attributed to the relatively large requirement for force production imposed on this transfer due to the average force requirements of the total plantar flexor group.

scholarly journals Excitability and contractility of skeletal muscle engineered from primary cultures and cell lines

2001 ◽  
Vol 280 (2) ◽  
pp. C288-C295 ◽  
Author(s):  
Robert G. Dennis ◽  
Paul E. Kosnik ◽  
Mark E. Gilbert ◽  
John A. Faulkner
Keyword(s):  
Skeletal Muscle ◽  
Relaxation Time ◽  
Cell Lines ◽  
Isometric Force ◽  
Cross Sectional Area ◽  
Specific Force ◽  
Sectional Area ◽  
Cross Sectional ◽  
Peak Tension ◽  
Time To Peak

The purpose of this study was to compare the excitability and contractility of three-dimensional skeletal muscle constructs, termed myooids, engineered from C2C12 myoblast and 10T½ fibroblast cell lines, primary muscle cultures from adult C3H mice, and neonatal and adult Sprague-Dawley rats. Myooids were 12 mm long, with diameters of 0.1–1 mm, were excitable by transverse electrical stimulation, and contracted to produce force. After ∼30 days in culture, myooid cross-sectional area, rheobase, chronaxie, resting baseline force, twitch force, time to peak tension, one-half relaxation time, and peak isometric force were measured. Specific force was calculated by dividing peak isometric force by cross-sectional area. The specific force generated by the myooids was 2–8% of that generated by skeletal muscles of control adult rodents. Myooids engineered from C2C12-10T½ cells exhibited greater rheobase, time to peak tension, and one-half relaxation time than myooids engineered from adult rodent cultures, and myooids from C2C12-10T½ and neonatal rat cells had greater resting baseline forces than myooids from adult rodent cultures.

scholarly journals Specific force of the vastus lateralis in adults with achondroplasia

2018 ◽  
Vol 124 (3) ◽  
pp. 696-703 ◽  
Author(s):  
David T. Sims ◽  
Gladys L. Onambélé-Pearson ◽  
Adrian Burden ◽  
Carl Payton ◽  
Christopher I. Morse
Keyword(s):  
Vastus Lateralis ◽  
Force Production ◽  
Limb Length ◽  
Muscle Size ◽  
Knee Extensors ◽  
Specific Force ◽  
Moment Arm ◽  
Cross Sectional ◽  
Volume Activation

Achondroplasia is a clinical condition defined by shorter stature and disproportionate limb length. Force production in able-bodied individuals (controls) is proportional to muscle size, but given the disproportionate nature of achondroplasia, normalizing to anatomical cross-sectional area (ACSA) is inappropriate. The aim of this study was to assess specific force of the vastus lateralis (VL) in 10 adults with achondroplasia (22 ± 3 yr) and 18 sex-matched controls (22 ± 2 yr). Isometric torque (iMVCτ) of the dominant knee extensors (KE) and in vivo measures of VL muscle architecture, volume, activation, and patella tendon moment arm were used to calculate VL physiological CSA (PCSA), fascicle force, and specific force in both groups. Achondroplasic muscle volume was 53% smaller than controls (284 ± 36 vs. 604 ± 102 cm3, P < 0.001). KE iMVCτ was 63% lower in achondroplasia compared with controls (95 ± 24 vs. 256 ± 47 N⋅m, P < 0.001). Activation and moment arm length were similar between groups ( P > 0.05), but coactivation of bicep femoris of achondroplasic subjects was 70% more than controls (43 ± 20 vs. 13 ± 5%, P < 0.001). Achondroplasic subjects had 58% less PCSA (43 ± 10 vs. 74.7 ± 14 cm2, P < 0.001), 29% lower fascicle force (702 ± 235 vs. 1704 ± 303 N, P < 0.001), and 29% lower specific force than control subjects (17 ± 6 vs. 24 ± 6 N⋅cm−2, P = 0.012). The smaller VL specific force in achondroplasia may be attributed to infiltration of fat and connective tissue, rather than to any difference in myofilament function. NEW & NOTEWORTHY The novel observation of this study was the measurement of normalized force production in a group of individuals with disproportionate limb length-to-torso ratios.

Advantage of normalizing force production to myofibrillar protein in skeletal muscle cross-sectional area

1994 ◽  
Vol 76 (2) ◽  
pp. 974-978 ◽  
Author(s):  
J. A. Taylor ◽  
S. C. Kandarian
Keyword(s):  
Soleus Muscle ◽  
Protein Concentration ◽  
Isometric Force ◽  
Force Production ◽  
Myofibrillar Protein ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Edl Muscle ◽  
Muscle Cross Sectional Area

When maximum isometric force (Po) is normalized to muscle cross-sectional area (CSA), intrinsic differences in force production among muscles may be masked by alterations in myofibrillar protein concentration or extracellular space. We tested the hypothesis that there is a greater deficit in Po when normalized to the average whole muscle CSA than when normalized to the myofibrillar protein CSA under conditions known to alter the concentration of myofibrils or connective tissue protein or interstitial fluid volume. Rats underwent either hindlimb unweighting (HU) to induce atrophy in the soleus muscle, sciatic nerve denervation to induce atrophy in the soleus and extensor digitorum longus (EDL) muscles, or ablation of gastrocnemius and plantaris muscles to induce hypertrophy in the soleus muscle. Po of the soleus muscle normalized to the muscle CSA (specific Po) was 58, 25, and 72% of control muscles with HU, denervation, and hypertrophy, respectively, whereas denervated EDL muscle specific Po was 60% of control muscles (P < 0.05). Soleus muscle Po normalized to the myofibrillar CSA was 80, 53, and 75% of control muscles with HU, denervation, and hypertrophy, respectively, whereas the denervated EDL muscle value was 82% of control muscles (P < 0.05). Both approaches to normalizing Po show force deficits, but normalization to the average myofibrillar protein in the muscle cross section gives values substantially closer to control values for HU and denervated muscles only. Data support the hypothesis because myofibrillar protein concentration is decreased in HU and denervation and interstitial space is increased in HU but neither parameter is altered with hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

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