scholarly journals Molecular Mechanisms of Muscle Tone Impairment under Conditions of Real and Simulated Space Flight

Acta Naturae ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 85-97
Author(s):  
Boris S. Shenkman ◽  
Andrey K. Tsaturyan ◽  
Ivan M. Vihlyantsev ◽  
Inessa B. Kozlovskaya ◽  
Anatoliy I. Grigoriev

Kozlovskaya et al. [1] and Grigoriev et al. [2] showed that enormous loss of muscle stiffness (atonia) develops in humans under true (space flight) and simulated microgravity conditions as early as after the first days of exposure. This phenomenon is attributed to the inactivation of slow motor units and called reflectory atonia. However, a lot of evidence indicating that even isolated muscle or a single fiber possesses substantial stiffness was published at the end of the 20th century. This intrinsic stiffness is determined by the active component, i.e. the ability to form actin-myosin cross-bridges during muscle stretch and contraction, as well as by cytoskeletal and extracellular matrix proteins, capable of resisting muscle stretch. The main facts on intrinsic muscle stiffness under conditions of gravitational unloading are considered in this review. The data obtained in studies of humans under dry immersion and rodent hindlimb suspension is analyzed. The results and hypotheses regarding reduced probability of cross-bridge formation in an atrophying muscle due to increased interfilament spacing are described. The evidence of cytoskeletal protein (titin, nebulin, etc.) degradation during gravitational unloading is also discussed. The possible mechanisms underlying structural changes in skeletal muscle collagen and its role in reducing intrinsic muscle stiffness are presented. The molecular mechanisms of changes in intrinsic stiffness during space flight and simulated microgravity are reviewed.

1997 ◽  
Vol 273 (1) ◽  
pp. R86-R92 ◽  
Author(s):  
E. Gallasch ◽  
M. Moser ◽  
I. B. Kozlovskaya ◽  
T. Kenner ◽  
A. Noordergraaf

Microgravity was used to study accelerometrically recorded microvibration (MV) and postural tremor (PT) at reduced muscle tone on one cosmonaut before, during, and after an 8-day space flight on the Russian Mir station. MV of the relaxed forearm in the 1 g environment showed the typical 7- to 13-Hz resonance oscillations triggered by the heart beat. In 0 g, these pulsations shifted to below 5 Hz and the waveform became similar to an ultralow frequency acceleration ballistocardiogram. PT of the arm stretched forward showed an irregular waveform in 1 g. In 0 g, the higher-frequency components were reduced and again an ultralow frequency ballistocardiogram emerged. As a control, hand force tremor was recorded as well; it was not affected by the gravity condition. A second-order analog with muscle stiffness (C) as parameter was used to evaluate the measurements. For MV it could be shown that cardiac impacts produce damped resonance oscillations when C is high enough (1 g). At low C (0 g), this resonance phenomenon is essentially filtered out. For PT both neuromuscular and cardiovascular forces produce an irregular output; when C is lowered (0 g) the higher-frequency content is strongly reduced. It is concluded that both MV and PT waveforms are sensitive to musculoskeletal stiffness, such that at the lowest stiffness achieved the cardiac impact dominates. In 1 g, the cosmonaut's data were not significantly different from the results in a control group (n = 6).


2021 ◽  
pp. 096452842110275
Author(s):  
Carolina Jiménez-Sánchez ◽  
Julio Gómez-Soriano ◽  
Elisabeth Bravo-Esteban ◽  
Orlando Mayoral-del Moral ◽  
Pablo Herrero-Gállego ◽  
...  

Background: Myofascial trigger points (MTrPs) are hypersensitive nodules in a taut band (TB) of skeletal muscle. Dry needling (DN) is an invasive technique recommended for the treatment of MTrPs. However, to our knowledge, no studies have investigated the influence of the DN technique on modification of muscle stiffness and neurophysiological properties of MTrPs. Objective: The objective was to examine the effect of DN on muscle stiffness and motoneuron excitability of a latent medial MTrP (nodule and TB) of the soleus muscle in non-injured subjects. Methods: A double-blinded randomised controlled trial of 46 subjects with latent medial MTrPs of the soleus was conducted, in which all received one session of DN. The intervention group (n = 23) were subjected to DN into the MTrP (the nodule), while the control group (n = 23) were subjected to DN into the TB. Assessment was carried out at baseline (pre-test), after the intervention (post-test) and 1 week after the intervention (follow-up). Biomechanical variables (muscle resistive force at 10°/s and 180°/s, muscle extensibility and strength), as measured with an isokinetic dynamometer, and neurophysiological variables (H-reflex), were recorded. Results: There were no statistically significant differences in biomechanical or neurophysiological assessments between groups. Considering the intra-group analysis, subjects in the intervention group exhibited increased maximal isometric voluntary force to ankle plantarflexion (MIVFp) at both post-intervention and follow-up assessment (p < 0.0125; 0.2 < d < 0.5), while no changes were found in the control group. Conclusion: One session of DN targeting latent MTrPs did not change muscle stiffness, muscle extensibility or motoneuron excitability. Further research on subjects with muscle tone disorders should be considered to better address the impact of DN on muscle tone. Trial registration number: NCT02575586 (ClinicalTrials.gov).


1994 ◽  
Vol 266 (5) ◽  
pp. C1257-C1262 ◽  
Author(s):  
Y. Ohira ◽  
K. Saito ◽  
T. Wakatsuki ◽  
W. Yasui ◽  
T. Suetsugu ◽  
...  

Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity.


2019 ◽  
Author(s):  
Kathryn P. Wall ◽  
Harold Hart ◽  
Thomas Lee ◽  
Cynthia Page ◽  
Taviare L. Hawkins ◽  
...  

ABSTRACTMicrotubules are biopolymers that perform diverse cellular functions. The regulation of microtubule behavior occurs in part through post-translational modification of both the α- and β- subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and glutamate residues to the disordered C-terminal tails of tubulin. Due to their prevalence in stable, high stress cellular structures such as cilia, we sought to determine if these modifications alter the intrinsic stiffness of microtubules. Here we describe the purification and characterization of differentially-modified pools of tubulin from Tetrahymena thermophila. We found that glycylation on the α-C-terminal tail is a key determinant of microtubule stiffness, but does not affect the number of protofilaments incorporated into microtubules. We measured the dynamics of the tail peptide backbone using nuclear magnetic resonance spectroscopy. We found that the spin-spin relaxation rate (R2) showed a pronounced decreased as a function of distance from the tubulin surface for the α-tubulin tail, indicating that the α-tubulin tail interacts with the dimer surface. This suggests that the interactions of the α-C-terminal tail with the tubulin body contributes to the stiffness of the assembled microtubule, providing insight into the mechanism by which glycylation and glutamylation can alter microtubule mechanical properties.SIGNIFICANCEMicrotubules are regulated in part by post-translational modifications including the heterogeneous addition of glycine and glutamate residues to the C-terminal tails. By producing and characterizing differentially-modified tubulin, this work provides insight into the molecular mechanisms of how these modifications alter intrinsic microtubule properties such as flexibility. These results have broader implications for mechanisms of how ciliary structures are able to function under high stress.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Konstantinos E Hatzistergos ◽  
Lauro M Takeuchi ◽  
Wayne Balkan ◽  
Joshua M Hare

Introduction: Space flight has profound negative impacts on cardiac health. Whereas microgravity appears to benefit cardiomyogenesis, long-duration space flight results in increased risk for cardiomyopathy. Here, we focused on cKit+ cardiac progenitor cells (CPCs) to elucidate the effects of microgravity in the heart. Hypothesis: Microgravity inhibits migration, proliferation and differentiation of CPCs. Methods: Adult heart tissue or induced pluripotent stem cells (iPSCs) from cKitCreErt2;IRG mice were grown for up to 24- (n=5) or 21-days (n=6), respectively, in static (SC) or a rotary cell-culture system (RCCS, simulated microgravity) in the presence of 4-OH tamoxifen to irreversibly label CPCs with EGFP. Expression of EGFP was quantified at selected time points in heart explants and iPSC-derived beating embryoid bodies (EBs). In addition, microarray analysis was performed on EBs at selected time points (n=11). Results: We found that, although explants in SC consistently produced EGFP+ CPCs with full capacity to proliferate and migrate, expression of EGFP was abolished in RCCS (p<0.05). Similarly, when day-4 EBs (formed via the hanging-drop method) were transferred to RCCS, they generated significantly fewer spontaneously beating EBs compared to EBs grown in SC (p=0.0005), whereas expression of EGFP in beating EBs was downregulated ~10-fold (p=0.01). Microarray analysis of EBs illustrated that the effect of CPs was accompanied by downregulation of genes related to migration, differentiation and development of the cardiac neural crest cell (CNC) lineage (i.e. Pax3, semaphorins, endothelin) without affecting the expression of cardiac mesoderm-related genes (i.e. GATA4, NKX2-5, MEF2C). Intriguingly, the effect of RCCS in CNC-related genes could be partly rescued upon transfer of EBs from RCCS to SC. Conclusions: cKit expression and CNC pathways are inhibited under simulated microgravity but can be reversed by returning to normal gravity. Our findings provide novel insights into the role of gravity in cardiomyogenesis and suggest that CPCs should be targeted therapeutically for the prevention and treatment of microgravity-induced cardiomyopathy.


2001 ◽  
Vol 280 (5) ◽  
pp. L965-L973 ◽  
Author(s):  
Catherine Benoit ◽  
Barbara Renaudon ◽  
Dany Salvail ◽  
Eric Rousseau

Epoxyeicosatrienoic acids (EETs) are produced from arachidonic acid via the cytochrome P-450 epoxygenase pathway. EETs are able to modulate smooth muscle tone by increasing K+ conductance, hence generating hyperpolarization of the tissues. However, the molecular mechanisms by which EETs induce smooth muscle relaxation are not fully understood. In the present study, the effects of EETs on airway smooth muscle (ASM) were investigated using three electrophysiological techniques. 8,9-EET and 14,15-EET induced concentration-dependent relaxations of the ASM precontracted with a muscarinc agonist (carbamylcholine chloride), and these relaxations were partly inhibited by 10 nM iberiotoxin (IbTX), a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker. Moreover, 3 μM 8,9- or 14,15-EET induced hyperpolarizations of −12 ± 3.5 and −16 ± 3 mV, with EC50 values of 0.13 and 0.14 μM, respectively, which were either reversed or blocked on addition of 10 nM IbTX. These results indicate that BKCa channels are involved in hyperpolarization and participate in the relaxation of ASM. In addition, complementary experiments demonstrated that 8,9- and 14,15-EET activate reconstituted BKCa channels at low free Ca2+ concentrations without affecting their unitary conductance. These increases in channel activity were IbTX sensitive and correlated well with the IbTX-sensitive hyperpolarization and relaxation of ASM. Together these results support the view that, in ASM, the EETs act through an epithelium-derived hyperpolarizing factorlike effect.


Author(s):  
Silvana Galvão ◽  
Denise Xerez ◽  
Renato de Lima ◽  
Alexandre V. Pino ◽  
Liliam Fernandes de Oliveira ◽  
...  

1979 ◽  
Vol 101 (1) ◽  
pp. 28-37 ◽  
Author(s):  
G. I. Zahalak ◽  
S. J. Heyman

This paper describes an investigation of the frequency-response characteristics of active human skeletal muscle in vivo over the frequency range 1 Hz to 15 Hz. The applied force, forearm position, and surface electromyograms (from biceps, triceps, and brachioradialis) were recorded simultaneously in four normal adult male subjects for small oscillations of the forearm about a mean position of 90 deg flexion. Two modes of oscillatory behavior are discussed: externally forced oscillations under constant muscle force and voluntary oscillations against an elastic resistance. The observed amplitude and phase relations are presented herein and are compared to the response predicted by a simple model for neuromuscular dynamics. It appears that the small amplitude frequency response of normal skeletal muscle in vivo can be represented by a second order model. The main muscle parameters of this model are a muscular stiffness K, two time constants τ1 and τ2 associated with contraction dynamics, and a time delay τ: typical values of these parameters at moderate contraction levels (approximately 20 percent of maximum voluntary effort) are K = 100 N · m/rad, τ1 and τ2 = 50 ms, and τ = 10 ms. Reflex feedback under forced-oscillation conditions was also examined and may be characterized by a gain parameter (ΔE/Δθ), the ratio of the surface EMG amplitude to the angular displacement of the forearm, and the phase by which the EMG leads muscle stretch. The reflex EMG is observed to lead muscle stretch at all frequencies between 1 Hz and 15 Hz. The muscle stiffness K and the reflex gain parameter (ΔE/Δθ) are approximately proportional to the average force of contraction.


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