scholarly journals Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/+ rat model of progressive kidney disease

2015 ◽  
pp. gfv352 ◽  
Author(s):  
Jason M. Organ ◽  
Andrew Srisuwananukorn ◽  
Paige Price ◽  
Jeffery E. Joll ◽  
Kelly C. Biro ◽  
...  
2010 ◽  
Vol 298 (1) ◽  
pp. C149-C162 ◽  
Author(s):  
Nadège Zanou ◽  
Georges Shapovalov ◽  
Magali Louis ◽  
Nicolas Tajeddine ◽  
Chiara Gallo ◽  
...  

Skeletal muscle contraction is reputed not to depend on extracellular Ca2+. Indeed, stricto sensu , excitation-contraction coupling does not necessitate entry of Ca2+. However, we previously observed that, during sustained activity (repeated contractions), entry of Ca2+is needed to maintain force production. In the present study, we evaluated the possible involvement of the canonical transient receptor potential (TRPC)1 ion channel in this entry of Ca2+and investigated its possible role in muscle function. Patch-clamp experiments reveal the presence of a small-conductance channel (13 pS) that is completely lost in adult fibers from TRPC1−/−mice. The influx of Ca2+through TRPC1 channels represents a minor part of the entry of Ca2+into muscle fibers at rest, and the activity of the channel is not store dependent. The lack of TRPC1 does not affect intracellular Ca2+concentration ([Ca2+]i) transients reached during a single isometric contraction. However, the involvement of TRPC1-related Ca2+entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1−/−mice stimulated repeatedly progressively display lower [Ca2+]itransients than those observed in TRPC1+/+fibers, and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1−/−mice display a smaller fiber cross-sectional area, generate less force per cross-sectional area, and contain less myofibrillar proteins than their controls. They do not present other signs of myopathy. In agreement with in vitro experiments, TRPC1−/−mice present an important decrease of endurance of physical activity. We conclude that TRPC1 ion channels modulate the entry of Ca2+during repeated contractions and help muscles to maintain their force during sustained repeated contractions.


2020 ◽  
Vol 33 ◽  
Author(s):  
Regiane Vidal ◽  
Gabriela Volkweis ◽  
Julye Leiko Ywazaki ◽  
Marco Antonio Ferreira Randi ◽  
Ana Paula Cunha Loureiro ◽  
...  

Abstract Introduction: Ageing is responsible for structural alterations, declining of all physiological variables, including range of motion and skeletal muscle function, known as sarcopenia. Objective: The aim of the study was to evaluate the effects of stretching on muscle morphometry in ovariectomized rats. Method: 21 female Wistar rats (12 weeks, 218 ± 22 g) were divided into 4 groups: control (CONTROL, n = 3) intact; ovariectomized and hysterectomized (OH, n = 6); Stretching (STRET, n = 6); ovariectomized and hysterectomized and stretching (OHS, n = 6). The rats were subjected to ovariectomy and hysterectomy. The stretching protocol of the soleus muscle lasted 10 repetitions of 1 minute with 45s interval between each repetition performed 3 times a week for 3 weeks. After 3 weeks, the rats were weighed and the muscles of both hind limbs were removed weighed and analyzed at muscle length; serial sarcomere number; sarcomere length; muscle fiber cross-sectional area (MFCSA) and percentage of connective tissue. Results: The final body weight increased in all groups. The serial sarcomere number of STRET was greater than the OH. The muscle fibers’ cross-sectional area of OHS was higher than CONTROL. Conclusion: It can be concluded that ovariectomy and hysterectomy prevented sarcomerogenesis even when stretching was applied. However, the stretching protocol enhanced muscle trophismof ovariectomized and hysterectomized rats. It might be suggested that longitudinal growth (serial sarcomeres) and radial (ASTFM) are differently regulated by stretching in intact and/or estrogen depleted (ovariectomy and hysterectomy) skeletal muscle.


2005 ◽  
Vol 61 (2) ◽  
Author(s):  
M. A. Gregory ◽  
M. N. Deane ◽  
M. Marsh

Objective: The precise mechanisms by which massage promotes repair in injured soft tissue are unknown. Various authorshave attributed the beneficial effects of massage to vasodilation and increased skin and muscle blood flow. The aim of this study was to determine whether deep transverse friction massage (DTF) causes capillary vasodilation in untraumatised skeletal muscle. Setting: Academic institution.Interventions: Twelve New Zealand white rabbits were anaesthetised and the left biceps femoris muscle received 10 minutes of DTF. Following treatment, wedge biopsies were taken from the musclewithin 10 minutes of treatment (R1 - 4), 24 hours (R5 - 8) and 6 days(R9 - 12) after treatment. To serve as controls, similar biopsies weretaken from the right biceps femoris of animals. The samples were fixed, dehydrated and embedded in epoxy resin.Transverse sections (1µm) of muscle were cut, stained with 1% aqueous alkaline toluidine blue and examined with a light microscope using a 40X objective. Images containing capillaries were captured using an image analyser with SIS software and the cross sectional diameters of at least 60 capillaries were measured from each specimen. Main Outcome Measures: Changes in capillary diameter. Results: The mean capillary diameters in control muscle averaged 4.76 µm. DTF caused a significant immediate increase of 17.3% in cross sectional area (p<0.001), which was not significantly increased by 10.0% after 24 hours (p>0.05). Six days after treatment the cross-sectional area of the treated muscle was 7.6% smaller than the controls. Conclusions: This confirms the contention that DTF stimulates muscle blood flow immediately after treatment and this may account for its beneficial effects in certain conditions. 


1998 ◽  
Vol 26 (4) ◽  
pp. 598-602 ◽  
Author(s):  
Donald T. Kirkendall ◽  
William E. Garrett

Aging results in a gradual loss of muscle function, and there are predictable age-related alterations in skeletal muscle function. The typical adult will lose muscle mass with age; the loss varies according to sex and the level of muscle activity. At the cellular level, muscles loose both cross-sectional area and fiber numbers, with type II muscle fibers being the most affected by aging. Some denervation of fibers may occur. The combination of these factors leads to an increased percentage of type I fibers in older adults. Metabolically, the glycolytic enzymes seem to be little affected by aging, but the aerobic enzymes appear to decline with age. Aged skeletal muscle produces less force and there is a general “slowing” of the mechanical characteristics of muscle. However, neither reduced muscle demand nor the subsequent loss of function is inevitable with aging. These losses can be minimized or even reversed with training. Endurance training can improve the aerobic capacity of muscle, and resistance training can improve central nervous system recruitment of muscle and increase muscle mass. Therefore, physical activity throughout life is encouraged to prevent much of the age-related impact on skeletal muscle.


2012 ◽  
Vol 303 (6) ◽  
pp. L519-L527 ◽  
Author(s):  
Vladimir T. Basic ◽  
Elsa Tadele ◽  
Ali Ateia Elmabsout ◽  
Hongwei Yao ◽  
Irfan Rahman ◽  
...  

Cigarette smoke (CS) is a well-established risk factor in the development of chronic obstructive pulmonary disease (COPD). In contrast, the extent to which CS exposure contributes to the development of the systemic manifestations of COPD, such as skeletal muscle dysfunction and wasting, remains largely unknown. Decreased skeletal muscle capillarization has been previously reported in early stages of COPD and might play an important role in the development of COPD-associated skeletal muscle abnormalities. To investigate the effects of chronic CS exposure on skeletal muscle capillarization and exercise tolerance, a mouse model of CS exposure was used. The 129/SvJ mice were exposed to CS for 6 mo, and the expression of putative elements of the hypoxia-angiogenic signaling cascade as well as muscle capillarization were studied. Additionally, functional tests assessing exercise tolerance/endurance were performed in mice. Compared with controls, skeletal muscles from CS-exposed mice exhibited significantly enhanced expression of von Hippel-Lindau tumor suppressor (VHL), ubiquitin-conjugating enzyme E2D1 (UBE2D1), and prolyl hydroxylase-2 (PHD2). In contrast, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was reduced. Furthermore, reduced muscle fiber cross-sectional area, decreased skeletal muscle capillarization, and reduced exercise tolerance were also observed in CS-exposed animals. Taken together, the current results provide evidence linking chronic CS exposure and induction of VHL expression in skeletal muscles leading toward impaired hypoxia-angiogenesis signal transduction, reduced muscle fiber cross-sectional area, and decreased exercise tolerance.


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Brian T. Bennett ◽  
Junaith S. Mohamed ◽  
Stephen E. Alway

Beta-hydroxy-beta-methylbutyrate (HMB), a naturally occurring leucine metabolite, has been shown to attenuate plantar flexor muscle loss and increase myogenic stem cell activation during reloading after a period of significant muscle wasting by disuse in old rodents. However, it was less clear if HMB would alter dorsiflexor muscle response to unloading or reloading when there was no significant atrophy that was induced by unloading. In this study, we tested if calcium HMB (Ca-HMB) would improve muscle function and alter apoptotic signaling in the extensor digitorum longus (EDL) of aged animals that were unloaded but did not undergo atrophy. The EDL muscle was unloaded for 14 days by hindlimb suspension (HS) in aged (34-36 mo.) male Fisher 344×Brown Norway rats. The rats were removed from HS and allowed normal cage ambulation for 14 days of reloading (R). Throughout the study, the rats were gavaged daily with 170 mg of Ca-HMB or water 7 days prior to HS, then throughout 14 days of HS and 14 days of recovery after removing HS. The animals’ body weights were significantly reduced by ~18% after 14 days of HS and continued to decline by ~22% during R as compared to control conditions; however, despite unloading, EDL did not atrophy by HS, nor did it increase in mass after R. No changes were observed in EDL twitch contraction time, force production, fatigue resistance, fiber cross-sectional area, or markers of nuclear apoptosis (myonuclei + satellite cells) after HS or R. While HS and R increased the proapoptotic Bax protein abundance, BCL-2 abundance was also increased as was the frequency of TUNEL-positive myonuclei and satellite cells, yet muscle mass and fiber cross-sectional area did not change and Ca-HMB treatment had no effect reducing apoptotic signaling. These data indicate that (i) increased apoptotic signaling preceded muscle atrophy or occurred without significant EDL atrophy and (ii) that Ca-HMB treatment did not improve EDL signaling, muscle mass, or muscle function in aged rats, when HS and R did not impact mass or function.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 222-222 ◽  
Author(s):  
Samuel Craig Brondfield ◽  
Vivian K. Weinberg ◽  
Kathryn M. Koepfgen ◽  
Arturo Molina ◽  
Charles J. Ryan ◽  
...  

222 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. Androgen deprivation therapy (ADT) has been shown to result in muscle wasting in prostate cancer pts. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential pts who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 pts were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, pts lost an average of 1.9 kg ± 1.9 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (−0.80 ± 1.71, p = 0.18) and total non-adipose mass (−1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (−0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in pts with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.


2005 ◽  
Vol 99 (3) ◽  
pp. 1085-1092 ◽  
Author(s):  
Nobuo Yasuda ◽  
Elisa I. Glover ◽  
Stuart M. Phillips ◽  
Robert J. Isfort ◽  
Mark A. Tarnopolsky

The purpose of this study was to determine the effects of short-term (14-day) unilateral leg immobilization using a simple knee brace (60° flexion)- or crutch-mediated model on muscle function and morphology in men (M, n = 13) and women (W, n = 14). Isometric and isokinetic (concentric-slow, 0.52 rad/s and fast, 5.24 rad/s) knee extensor peak torque was determined at three time points (Pre, Day-2, and Day-14). At the same time points, magnetic resonance imaging was used to measure the cross-sectional area of the quadriceps femoris and dual-energy X-ray absorptiometry scanning was used to calculate leg lean mass. Muscle biopsies were taken from vastus lateralis at Pre and Day-14 for myosin ATPase and myosin heavy chain analysis. Women showed greater decreases (Pre vs. Day-14) compared with men in specific strength (N/cm2) for isometric [M = 3.1 ± 13.3, W = 17.1 ± 15.9%; P = 0.055 (mean ± SD)] and concentric-slow (M = 4.7 ± 11.3, W = 16.6 ± 18.4%; P < 0.05) contractions. There were no immobilization-induced sex-specific differences in the decrease in quadriceps femoris cross-sectional area (M = 5.7 ± 5.0, W = 5.9 ± 5.2%) or leg lean mass (M = 3.7 ± 4.2, W = 2.7 ± 2.8%). There were no fiber-type transformations, and the decreases in type I (M = 4.8 ± 5.0, W = 5.9 ± 3.4%), IIa (M = 7.9 ± 9.9, W = 8.8 ± 8.0%), and IIx (M = 10.7 ± 10.8, W = 10.8 ± 12.1%) fiber areas were similar between sexes. These findings indicate that immobilization-induced loss of knee extensor muscle strength is greater in women compared with men despite a similar extent of atrophy at the myofiber and whole muscle levels after 14 days of unilateral leg immobilization. Furthermore, we have described an effective and safe knee immobilization method that results in reductions in quadriceps muscle strength and size.


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