scholarly journals Skeletal muscle contractile properties in a novel murine model for limb girdle muscular dystrophy 2i

2017 ◽  
Vol 123 (6) ◽  
pp. 1698-1707 ◽  
Author(s):  
Jordan D. Rehwaldt ◽  
Buel D. Rodgers ◽  
David C. Lin
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Muscle Function ◽  
Contractile Properties ◽  
Limb Girdle Muscular Dystrophy ◽  
Medial Gastrocnemius ◽  
Active Force ◽  
Wild Type ◽  
Muscle Contractile Properties ◽  
Muscle Contractile

Limb-girdle muscular dystrophy (LGMD) 2i results from mutations in fukutin-related protein and aberrant α-dystroglycan glycosylation. Although this significantly compromises muscle function and ambulation, the comprehensive characteristics of contractile dysfunction are unknown. Therefore, we quantified the in situ contractile properties of the medial gastrocnemius in young adult P448L mice, an affected muscle of a novel model of LGMD2i. Normalized maximal twitch force, tetanic force, and power were significantly smaller in P448L mice, compared with sex-matched, wild-type mice. These differences were consistent with the replacement of contractile fibers by passive tissue. The shape of the active force-length relationships were similar in both groups, regardless of sex, consistent with an intact sarcomeric structure in P448L mice. Passive force-length curves normalized to maximal isometric force were steeper in P448L mice, and passive elements contribute disproportionately more to total contractile force in P448L mice. Sex differences were mostly noted in the force-velocity curves, as normalized values for maximal and optimal velocities were significantly slower in P448L males, compared with wild-type, but not in P448L females. This suggests that the dystrophic phenotype, which may include possible changes in cross-bridge kinetics and fiber-type proportions, progresses more quickly in P448L males. These results together indicate that active force and power generation are compromised in both sexes of P448L mice, while passive forces increase. More importantly, the results identified several functional markers of disease pathophysiology that could aid in developing and assessment of novel therapeutics for LGMD2i and possibly other dystroglycanopathies as well. NEW & NOTEWORTHY Comprehensive assessments of muscle contractile function have, until now, never been performed in an animal model for any dystroglycanopathy. This study suggests that skeletal muscle contractile properties are significantly compromised in a recently developed model for limb-girdle muscular dystrophy 2i, the P448L mouse. It further identifies novel pathological markers of muscle function that are suitable for developing therapeutics and for better understanding of disease pathogenesis.

Sexually dimorphic skeletal muscle and cardiac dysfunction in a mouse model of limb girdle muscular dystrophy 2i

2017 ◽  
Vol 123 (5) ◽  
pp. 1126-1138 ◽  
Author(s):  
Joseph W. Maricelli ◽  
Denali R. Kagel ◽  
Yemeserach M. Bishaw ◽  
O. Lynne Nelson ◽  
David C. Lin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Muscle Function ◽  
Mutant Mouse ◽  
Striated Muscle ◽  
Cardiac Performance ◽  
Limb Girdle Muscular Dystrophy ◽  
Voluntary Exercise ◽  
Drug Trials ◽  
Wild Type

The fukutin-related protein P448L mutant mouse replicates many pathologies common to limb girdle muscular dystrophy 2i (LGMD2i) and is a potentially strong candidate for relevant drug screening studies. Because striated muscle function remains relatively uncharacterized in this mouse, we sought to identify metabolic, functional and histological metrics of exercise and cardiac performance. This was accomplished by quantifying voluntary exercise on running wheels, forced exercise on respiratory treadmills and cardiac output with echocardiography and isoproterenol stress tests. Voluntary exercise revealed few differences between wild-type and P448L mice. By contrast, peak oxygen consumption (VO2peak) was either lower in P448L mice or reduced with repeated low intensity treadmill exercise while it increased in wild-type mice. P448L mice fatigued quicker and ran shorter distances while expending 2-fold more calories/meter. They also received over 6-fold more motivational shocks with repeated exercise. Differences in VO2peak and resting metabolic rate were consistent with left ventricle dysfunction, which often develops in human LGMD2i patients and was more evident in female P448L mice, as indicated by lower fractional shortening and ejection fraction values and higher left ventricle systolic volumes. Several traditional markers of dystrophinopathies were expressed in P448L mice and were exacerbated by exercise, some in a muscle-dependent manner. These include elevated serum creatine kinase and muscle central nucleation, smaller muscle fiber cross-sectional area and more striated muscle fibrosis. These studies together identified several markers of disease pathology that are shared between P448L mice and human subjects with LGMD2i. They also identified novel metrics of exercise and cardiac performance that could prove invaluable in preclinical drug trials.NEW & NOTEWORTHY Limb-girdle muscular dystrophy 2i is a rare dystroglycanopathy that until recently lacked an appropriate animal model. Studies with the FKRP P448L mutant mouse began assessing muscle structure and function as well as running gait. Our studies further characterize systemic muscle function using exercise and cardiac performance. They identified many markers of respiratory, cardiac and skeletal muscle function that could prove invaluable to better understanding the disease and more importantly, to preclinical drug trials.

scholarly journals Procedures for Rat in situ Skeletal Muscle Contractile Properties

10.3791/3167 ◽  
2011 ◽  
Author(s):  
Brian R. MacIntosh ◽  
Shane P. Esau ◽  
R. John Holash ◽  
Jared R. Fletcher
Keyword(s):  
Skeletal Muscle ◽  
Contractile Properties ◽  
Muscle Contractile Properties ◽  
Muscle Contractile

Effect of caffeine on skeletal muscle function before and after fatigue

1983 ◽  
Vol 54 (5) ◽  
pp. 1303-1305 ◽  
Author(s):  
J. M. Lopes ◽  
M. Aubier ◽  
J. Jardim ◽  
J. V. Aranda ◽  
P. T. Macklem
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Relaxation Rate ◽  
Voluntary Contraction ◽  
Contractile Properties ◽  
Double Blind ◽  
Caffeine Ingestion ◽  
Muscle Contractile Properties ◽  
Before And After ◽  
Muscle Contractile

We studied the effect of caffeine on voluntary and electrically stimulated contractions of the adductor pollicis muscle in five adult volunteers. Caffeine (500 mg) was administered orally in a double-blind fashion. Electrical stimulation of the ulnar nerve was performed at 10, 20, 30, 50, and 100 Hz before and after a sustained voluntary contraction held at 50% of the maximal voluntary contraction (MVC). A brief tetanus at 30 Hz was also performed to calculate relaxation rate in the fresh muscle. Contractile properties, relaxation rate, and endurance were then assessed after caffeine and placebo, as well as the response of the fatigued muscle to different frequencies of stimulation. There was no difference in the maximal tension obtained with electrical stimulation (T100) or in the MVC between placebo and caffeine. The tensions developed with electrical stimulation at lower frequencies increased significantly with caffeine ingestion, shifting the frequency-force curve to the left, both before and after fatigue. Mean plasma caffeine concentration associated with these responses was 12.2 +/- 4.9 mg/l. We conclude that caffeine has a direct effect on skeletal muscle contractile properties both before and after fatigue as demonstrated by electrical stimulation.

Effect of Cold-Water Immersion on Skeletal Muscle Contractile Properties in Soccer Players

2011 ◽  
Vol 90 (5) ◽  
pp. 356-363 ◽  
Author(s):  
Juan Manuel García-Manso ◽  
Darío Rodríguez-Matoso ◽  
David Rodríguez-Ruiz ◽  
Samuel Sarmiento ◽  
Yves de Saa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cold Water ◽  
Water Immersion ◽  
Cold Water Immersion ◽  
Contractile Properties ◽  
Soccer Players ◽  
Muscle Contractile Properties ◽  
Muscle Contractile

scholarly journals Peanut protein reduces body protein mass and alters skeletal muscle contractile properties and lipid metabolism in rats

2009 ◽  
Vol 103 (9) ◽  
pp. 1331-1339 ◽  
Author(s):  
Hélène Jacques ◽  
Nadine Leblanc ◽  
Roxanne Papineau ◽  
Denis Richard ◽  
Claude H. Côté
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Lipid Metabolism ◽  
Liver Weight ◽  
Peanut Protein ◽  
Contractile Properties ◽  
Body Protein ◽  
Protein Mass ◽  
Muscle Contractile Properties ◽  
Muscle Contractile

It is well known that diets high in nuts or peanuts favourably affect plasma lipid concentrations. However, few studies have examined the effects of nut and peanut protein (PP) on body composition and skeletal muscle properties. The present study was aimed at evaluating the effect of dietary PP compared with two animal proteins, casein (C) and cod protein (CP) on body composition, skeletal muscle contractile properties and lipid metabolism in rats. Thirty-two male rats were assigned to one of the following four diets containing either C, CP, PP or C+peanut protein (CPP, 50:50) mixture. After 28 d of ad libitum feeding and after 12-h fast, blood, liver and muscle were collected for measurements of plasma and hepatic cholesterol and TAG, plasma glucose and insulin and contractile properties. Rats fed with the low-quality protein, PP, had lower body weight gain, body protein mass, soleus mass and liver weight than those fed with the high-quality dietary proteins, C and CP. PP also caused a deficit in contractile properties in soleus. Likewise, PP increased plasma cholesterol and body fat mass compared with CP. However, these elevations were accompanied with increased hepatic TAG concentrations and lowered intestinal fat excretion. These results show that PP intake alters body composition by reducing skeletal muscle mass and liver weight as well as muscle contractility and lipid metabolism. Adding a complete protein such as C might partially counteract these adverse effects.

scholarly journals Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males

2014 ◽  
Vol 114 (6) ◽  
pp. 1309-1320 ◽  
Author(s):  
Daniel J. Owens ◽  
Daniel Webber ◽  
Samuel G. Impey ◽  
Jonathan Tang ◽  
Timothy F. Donovan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Human Skeletal Muscle ◽  
Vitamin D Supplementation ◽  
Contractile Properties ◽  
Young Males ◽  
Muscle Contractile Properties ◽  
Muscle Contractile
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