A Strategy for Research in Space Biology and Medicine in the New Century (1998) / Chapter Skim
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7 Skeletal Muscle
7 Skeletal Muscle
Pages 97-117
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From page 97... ...
The other measures may include strategies such as the concomitant utilization of hormones, growth factors, drugs, and lower-body negative-pressure devices. To date, microgravity has been only minimally exploited as a unique tool for understanding the fundamental mechanisms that underlie its effects on neuromuscular function and provide the basis for development of effective countermeasures.
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From page 98... ...
Most spaceflight investigations have focused on growing or mature animals. Preliminary spaceflight results and hindlimb unloading studies involving developing animals suggest that gravity loading may not only be necessary for the maintenance of mature skeletal muscle but may also be essential for differentiation of the developing neuromuscular system in a direction appropriate for functioning efficiently in terrestrial gravity.
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From page 99... ...
The phenotype of the secondary fibers is modulated by impulse patterns from the motor innervation. Thyroid hormone levels can also profoundly affect expression of myosin heavy and light chain isoforms.~2~3 Mounting evidence indicates that cis- and trans-acting regulatory factors, as yet uncharacterized, control specific fiber-type differentiation at the transcriptional level.~4 Myogenin mRNA levels are higher in slow fibers, and MyoD transcript levels are higher in fast fibers.~5 The characterization of cis- and trans-acting factors that regulate transcription of fiber-type-specific protein isoforms is an important area to pursue in understanding muscle plasticity.
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From page 100... ...
results indicate that gravity loading is required for normal development of the neuromuscular system of the weight-bearing soleus muscle, whereas loading is not critical for the non-weight-bearing extensor digitorum longus muscle. In the absence of weight-bearing, soleus muscle fibers failed to grow in size and differentiate normally into slow fibers, and elaboration of the motor nerve terminals was retarded.
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From page 101... ...
The metabolically adapted cells are better equipped biochemically to derive energy anaerobically and tolerate ischemia.58~60 The reduced blood flow in and dehydration of the leg muscles cause enhanced heart rate responses. The adaptation toward glycolysis is as yet unexplained and is accompanied by a compromised ability to oxidize long-chain fatty acids.62 This shift has the downside of rendering the muscle more fatigable, even though the capacity to transport glucose is enhanced.63 64 The shift in metabolism is evident in the increased content of glycolytic energy-deriving enzymes, elevated storage of glycogen, and disappearance of peripheral mitochondria.65~69 Following bed rest, glycogen storage increased within the I bands and occupied spaces within myofibrils vacated by thin filaments lost during fiber atrophy.70 Astronauts and rats returning from a short-duration spaceflight of 1 to 2 weeks may experience muscle fatigue, weakness, incoordination, and delayed-onset muscle soreness.7~~73 The greater reliance on glycolysis contributes to the reduced endurance and increased fatigability.
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From page 102... ...
The elevated speed of shortening, resulting from decreased contractile-filament packing density and increased fast myosin expression, compensates for the reduced force by diminishing the loss in power output (power is the product of velocity times force) .~09~~3 Another example is the increased capillary density and cross-sectional area of tissue that occurs when muscle fibers shrink more rapidly than the downsizing of the microvascular network.~4 ll5 This theoretically compensates for lower blood flow and greater susceptibility to fatigue because the average diffusion distance is decreased from the capillary to the centers of muscle fibers.
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From page 103... ...
Spaceflown rats walked significantly more slowly than normal the first 2 days, but they moved as rapidly as ground controls by the third day. The jerky, stilted stepping of the hindlimbs quickly evolved to the smooth walking pattern of a terrestrially readapted rat.~27 Unloading studies with immature rats indicate that gravity loading during the third and fourth weeks after birth is essential for normal development of 1-g locomotion.
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From page 104... ...
It appears that underused microvessels adapt to low flow and pressure during spaceflight or HU and may become inherently "more leaky" during the rapid onset of high blood flow and pressure when gravity-loaded muscle contractions are resumed.~60~~62 Furthermore, the unloading-induced shift to glycolytic metabolism away from oxidative metabolism results in a more robust stimulation of blood pressure during muscle contraction.~63 The results suggest that avoiding strenuous muscle contractions during reacclimatization to gravity and possibly medicating before landing with drugs that block mast cell degranulation may minimize edema in returning astronauts. Possible countermeasures that should be investigated to minimize reentry and reloading-induced edema and ischemic tissue necrosis include flushing the interstitium of excess proteins by exercise-induced muscle contractions, combined with lower body negative pressure (LBNP)
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From page 105... ...
involves autocrine/paracrine growth factors signal transduction, immediate-early genes, and multiple second messengers (phospholipase, eicosinoids, tyrosine kineses, RAF-1, MAP kineses, stretch-activated ion channels, and protein translation regulators) .204 The in vitro model of applying stretch to skeletal muscle cells has shown a convincing correlation between active tension and prostaglandin release; these autocrine factors modulate protein degradation and synthesis.205 Absence of a single component protein of the dystrophin glycoprotein complex can result in greater susceptibility to contraction-induced sarcolemma tearing.206~208 This is seen in human dystrophies and mouse dystrophy mutants.209 Muscles of the mdx dystrophic mouse are more easily torn during contraction than the same muscles in normal animals.2l0 HU renders the atrophic soleus muscle more susceptible to contraction-induced muscle tearing.21 1 The nonatrophic extensor digitorum longus muscle in the same animals did not exhibit increased vulnerability.212 Fortunately, genetically normal muscle fibers rapidly repair sarcomere lesions by Z-line-like patching and restore segmental necrosis by membrane sealing and satellite cell regeneration.2l3~2l7 In human muscles, the number of satellite cell divisions normally may be limited.
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From page 106... ...
Microgravity has proven an excellent tool for noninvasively perturbing the synthesis of muscle proteins in the search for molecular signals and gene regulatory factors influencing differentiation, growth, maintenance, plasticity, and atrophy of muscle. The relationships between blood flow history and interstitial edema and between workload history and structural failure are but two of the important problems that require serious attention.
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From page 107... ...
Development from conception to the mature adult and the F1 generations are needed to determine whether critical periods require gravitation influences for normal gene expression.223 As described in other chapters of this report, a key question is how cells detect the effects of gravity. The myotendinous junctions and costameres are the most likely sites at which loading imparts stresses on the connective tissues and tendons and the basement membrane, which signals through integral membrane proteins to the cytoskeleton and contractile proteins.224~226 These pathways will involve multiple second messengers, such as signaling through kinase activation and eicosinoids.227 Mechanisms of sensing working length remain undefined.
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From page 108... ...
The mechanisms should be determined whereby muscle cells sense working length and the mechanical stress of gravity. Signal transduction pathways for growth factors, stretch-activated ion channels, regulators of protein synthesis, and interactions of extracellular matrix and membrane proteins with cytoskeleton should be investigated.
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From page 109... ...
1987. Hypogravity-induced atrophy of rat soleus and extensor digitorum longus muscles.
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From page 110... ...
1994. Force-velocity and power characteristics of rat soleus muscle fibers after hindlimb suspension.
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From page 111... ...
1994. Force-velocity and power characteristics of rat soleus muscle fibers after hindlimb suspension.
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From page 112... ...
1994. Force-velocity and power characteristics of rat soleus muscle fibers after hindlimb suspension.
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From page 113... ...
1997. Effect of 17 days bedrest on peak isometric force and maximal shortening velocity of human soleus fibers.
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From page 114... ...
1987. Hypogravity-induced atrophy of rat soleus and extensor digitorum longus muscles.
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From page 115... ...
1987. Hypogravity-induced atrophy of rat soleus and extensor digitorum longus muscles.
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From page 116... ...
1995. Review of spaceflight and hindlimb suspension unloading induced sarcomere damage and repair.
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From page 117... ...
1995. Review of spaceflight and hindlimb suspension unloading induced sarcomere damage and repair.
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