scholarly journals Skeletal muscle function and water permeability in aquaporin-4 deficient mice

2000 ◽  
Vol 278 (6) ◽  
pp. C1108-C1115 ◽  
Author(s):  
Baoxue Yang ◽  
Jean-Marc Verbavatz ◽  
Yuanlin Song ◽  
L. Vetrivel ◽  
Geoffrey Manley ◽  
...  

It has been proposed that aquaporin-4 (AQP4), a water channel expressed at the plasmalemma of skeletal muscle cells, is important in normal muscle physiology and in the pathophysiology of Duchenne's muscular dystrophy. To test this hypothesis, muscle water permeability and function were compared in wild-type and AQP4 knockout mice. Immunofluorescence and freeze-fracture electron microscopy showed AQP4 protein expression in plasmalemma of fast-twitch skeletal muscle fibers of wild-type mice. Osmotic water permeability was measured in microdissected muscle fibers from the extensor digitorum longus (EDL) and fractionated membrane vesicles from EDL homogenates. With the use of spatial-filtering microscopy to measure osmotically induced volume changes in EDL fibers, half times ( t 1/2) for osmotic equilibration (7.5–8.5 s) were not affected by AQP4 deletion. Stopped-flow light-scattering measurements of osmotically induced volume changes in plasmalemma vesicles also showed no significant differences in water permeability. Similar water permeability, yet ∼90% decreased AQP4 protein expression was found in EDL from mdx mice that lack dystrophin. Skeletal muscle function was measured by force generation in isolated EDL, treadmill performance time, and in vivo muscle swelling in response to water intoxication. No differences were found in EDL force generation after electrical stimulation [42 ± 2 (wild-type) vs. 41 ± 2 (knockout) g/s], treadmill performance time (22 vs. 26 min; 29 m/min, 13° incline), or muscle swelling (2.8 vs. 2.9% increased water content at 90 min after intraperitoneal water infusion). Together these results provide evidence against a significant role of AQP4 in skeletal muscle physiology in mice.

2020 ◽  
Vol 21 (20) ◽  
pp. 7466
Author(s):  
Frank J. Raucci ◽  
Anand Prakash Singh ◽  
Jonathan Soslow ◽  
Larry W. Markham ◽  
Lin Zhong ◽  
...  

Brain-derived neurotrophic factor (BDNF) is a neuronal growth and survival factor that harbors cardioprotective qualities that may attenuate dilated cardiomyopathy. In ~30% of the population, BDNF has a common, nonsynonymous single nucleotide polymorphism rs6265 (Val66Met), which might be correlated with increased risk of cardiovascular events. We previously showed that BDNF correlates with better cardiac function in Duchenne muscular dystrophy (DMD) patients. However, the effect of the Val66Met polymorphism on cardiac function has not been determined. The goal of the current study was to determine the effects of rs6265 on BDNF biomarker suitability and DMD cardiac functions more generally. We assessed cardiovascular and skeletal muscle function in human DMD patients segregated by polymorphic allele. We also compared echocardiographic, electrophysiologic, and cardiomyocyte contractility in C57/BL-6 wild-type mice with rs6265 polymorphism and in mdx/mTR (mDMD) mouse model of DMD. In human DMD patients, plasma BDNF levels had a positive correlation with left ventricular function, opposite to that seen in rs6265 carriers. There was also a substantial decrease in skeletal muscle function in carriers compared to the Val homozygotes. Surprisingly, the opposite was true when cardiac function of DMD carriers and non-carriers were compared. On the other hand, Val66Met wild-type mice had only subtle functional differences at baseline but significantly decreased cardiomyocyte contractility. Our results indicate that the Val66Met polymorphism alters myocyte contractility, conferring worse skeletal muscle function but better cardiac function in DMD patients. Moreover, these results suggest a mechanism for the relative preservation of cardiac tissues compared to skeletal muscle in DMD patients and underscores the complexity of BDNF signaling in response to mechanical workload.


2003 ◽  
Vol 27 (4) ◽  
pp. 171-182
Author(s):  
Susan V. Brooks

Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest both scientifically and clinically. Injury, disease, and old age are among the factors that commonly contribute to impairment in skeletal muscle function. The goal of this article is to update current concepts of skeletal muscle physiology. Particular emphasis is placed on mechanisms of injury, repair, and adaptation in skeletal muscle as well as mechanisms underlying the declining skeletal muscle structure and function associated with aging. For additional materials please refer to the “Skeletal Muscle Physiology” presentation located on the American Physiological Society Archive of Teaching Resources Web site ( https://www.lifescitrc.org ).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Z. Darabseh ◽  
Thomas M. Maden-Wilkinson ◽  
George Welbourne ◽  
Rob C. I. Wüst ◽  
Nessar Ahmed ◽  
...  

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.


2009 ◽  
Vol 602 (1) ◽  
pp. 143-147 ◽  
Author(s):  
Benoît Giannesini ◽  
Marguerite Izquierdo ◽  
Yann Le Fur ◽  
Patrick J. Cozzone ◽  
Marc Verleye ◽  
...  

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michael D. Tarpey ◽  
Adam J. Amorese ◽  
Elizabeth R. LaFave ◽  
Everett C. Minchew ◽  
Kelsey H. Fisher-Wellman ◽  
...  

1990 ◽  
pp. 647-654
Author(s):  
Richard L. Mooney ◽  
Gerald C. Llewellyn ◽  
T. Daniel Kimbrough

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