scholarly journals PO-064 A potential role of stretch-activated channels in anabolic mechanotransduction in the atrophied rat soleus muscle

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Timur Mirzoev ◽  
Sergey Tyganov ◽  
Boris Shenkman
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Contractile Function ◽  
Mammalian Skeletal Muscle ◽  
Mechanical Unloading ◽  
Mtorc1 Signaling ◽  
Significant Difference ◽  
Rat Soleus Muscle ◽  
Isolated Rat

Objective Prolonged immobilization or unloading of skeletal muscle causes muscle disuse atrophy, which is characterized by a reduction in muscle cross-sectional area and compromised contractile function. To date, the mechanisms of anabolic mechanotransduction in the atrophied mammalian skeletal muscle remain poorly understood. The aim of the present study was to assess a possible role of stretch-activated ion channels (SAC) in the propagation of a mechanical signal to anabolic signaling and protein synthesis (PS) in an isolated rat soleus muscle following mechanical unloading. Methods The mechanical unloading was performed via hindlimb suspension (HS). Twenty-eight male Wistar rats weighing were randomly assigned to the following 4 groups (n=7/group): 1) vivarium control (C), 2) control + SAC inhibitor (gadolinium) (C+Gd3+), 3) 7-day HS (HS), 4) 7-day HS + SAC inhibitor (HS+Gd3+). Following unloading, an isolated rat soleus was placed in an organ culture medium and subjected to a bout of eccentric contractions (EC). Upon completion of the EC, muscles were collected for Western blot analyses to determine the content of the key anabolic markers. The rate of PS was measured by SUnSET technique. Results EC-induced increase in PS was significantly less in the HS and HS+ Gd3+ groups vs. the C group. There was no statistically significant difference between the HS and HS+ Gd3+ groups in terms of EC-induced increase in muscle PS. A decrease in EC-induced phosphorylation of p70S6K, 4E-BP1, RPS6 and GSK-3beta in the 7-day unloaded soleus treated with SAC inhibitor did not differ from that of the 7-day unloaded soleus without SAC blockade. Thus, the inhibition of SAC with gadolinium did not lead to further decline in EC-induced phosphorylation of the key anabolic markers and muscle PS. Conclusions The results of the study suggest that attenuation of mTORC1-signaling and PS in response to EC in unloaded soleus muscle may be associated with inactivation of SAC. The study was supported by the RFBR grant # 16-34-60055.

On the role of 5-hydroxytryptamine in the peripheral action of fenfluramine: studies with the isolated rat soleus muscle

1990 ◽  
Vol 39 (5) ◽  
pp. 965-968 ◽  
Author(s):  
Shlomo Sasson ◽  
Baruch Kunievsky ◽  
Christine Nathan ◽  
Erol Ceras
Keyword(s):  
Soleus Muscle ◽  
Rat Soleus Muscle ◽  
Peripheral Action ◽  
Isolated Rat

The importance of limitations in aerobic metabolism, glycolysis, and membrane excitability for the development of high-frequency fatigue in isolated rat soleus muscle

2007 ◽  
Vol 292 (5) ◽  
pp. R2001-R2011 ◽  
Author(s):  
K. T. Murphy ◽  
T. Clausen
Keyword(s):  
Soleus Muscle ◽  
High Frequency ◽  
Receptor Agonist ◽  
Aerobic Metabolism ◽  
Membrane Excitability ◽  
M Wave ◽  
Force Transducers ◽  
Rat Soleus Muscle ◽  
Isolated Rat

We investigated the role of limitations in aerobic metabolism, glycolysis, and membrane excitability for development of high-frequency fatigue in isolated rat soleus muscle. Muscles mounted on force transducers were incubated in buffer bubbled with 5% CO2 and either 95% O2 (oxygenated) or 95% N2 (anoxic) and stimulated at 60 Hz continuously for 30–120 s or intermittently for 120 s. Cyanide (2 mM) and 2-deoxyglucose (10 mM) were used to inhibit aerobic metabolism and both glycolysis and aerobic metabolism, respectively. Excitability was reduced by carbacholine (10 μM), a nicotinic ACh receptor agonist, or ouabain (10 μM), an Na+-K+ pump inhibitor. Membrane excitability was measured by recording M waves. Intracellular Na+ and K+ contents and membrane potentials were measured by flame photometry and microelectrodes, respectively. During 120 s of continuous stimulation, oxygenated and anoxic muscles showed the same force loss. In oxygenated muscles, cyanide did not alter force loss for up to 90 s, whereas 2-deoxyglucose increased force loss (by 19–69%; P < 0.01) from 14 s of stimulation. In oxygenated muscles, 60 s of stimulation reduced force, M wave area, and amplitude by 70–90% ( P < 0.001). Carbacholine or ouabain increased intracellular Na+ content ( P < 0.001), induced a 7- to 8-mV membrane depolarization ( P < 0.001), and accelerated the rate of force loss (by 250–414%) during 30 s of stimulation ( P < 0.001). Similar effects were seen with intermittent stimulation. In conclusion, limitations in glycolysis and subsequently also in aerobic metabolism, as well as membrane excitability but not aerobic metabolism alone, appear to play an important role in the development of high-frequency fatigue in isolated rat soleus muscle.

scholarly journals Factors determining the subunit composition of tropomyosin in mammalian skeletal muscle

1985 ◽  
Vol 226 (2) ◽  
pp. 461-468 ◽  
Author(s):  
D H Heeley ◽  
G K Dhoot ◽  
S V Perry
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Reciprocal Relationship ◽  
Mammalian Skeletal Muscle ◽  
Adult Rat ◽  
Fast Twitch Muscle ◽  
Rat Soleus Muscle ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Developing Muscle

Adult rat fast-twitch skeletal muscle such as extensor digitorum longus contains alpha- and beta-tropomyosin subunits, as is the case in the corresponding muscles of rabbit. Adult rat soleus muscle contains beta-, gamma- and delta-tropomyosins, but no significant amounts of alpha-tropomyosin. Evidence for the presence of phosphorylated forms of at least three of the four tropomyosin subunit isoforms was obtained, particularly in developing muscle. Immediately after birth alpha- and beta-tropomyosins were the major components of skeletal muscle, in both fast-twitch and slow-twitch muscles. Differentiation into slow-twitch skeletal muscles was accompanied by a fall in the amount of alpha-tropomyosin subunit and its replacement with gamma- and delta-subunits. After denervation and during regeneration after injury, the tropomyosin composition of slow-twitch skeletal muscle changed to that associated with fast-twitch muscle. Thyroidectomy slowed down the changes in tropomyosin composition resulting from the denervation of soleus muscle. The results suggest that the ‘ground state’ of tropomyosin-gene expression in the skeletal muscle gives rise to alpha- and beta-tropomyosin subunits. Innervation by a ‘slow-twitch’ nerve is essential for the expression of the genes controlling gamma- and delta-subunits. There appears to be reciprocal relationship between expression of the gene controlling the synthesis of alpha-tropomyosin and those controlling the synthesis of gamma- and delta-tropomyosin subunits.

scholarly journals Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle

2021 ◽  
Vol 22 (8) ◽  
pp. 3920
Author(s):  
Violetta V. Kravtsova ◽  
Inna I. Paramonova ◽  
Natalia A. Vilchinskaya ◽  
Maria V. Tishkova ◽  
Vladimir V. Matchkov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Single Injection ◽  
Chronic Administration ◽  
Motor Dysfunction ◽  
Hindlimb Suspension ◽  
Muscle Disuse ◽  
Rat Soleus Muscle ◽  
Amp Activated Protein Kinase ◽  
Specific Ligand

Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is characteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis and prevents its disuse-induced disturbances. Isolated soleus muscles from rats intraperitoneally injected with ouabain alone or subsequently exposed to muscle disuse by 6-h hindlimb suspension (HS) were studied. Conventional electrophysiology, Western blotting, and confocal microscopy with cytochemistry were used. Acutely applied 10 nM ouabain hyperpolarized the membrane. However, a single injection of ouabain (1 µg/kg) prior HS was unable to prevent the HS-induced membrane depolarization. Chronic administration of ouabain for four days did not change the α1 and α2 Na,K-ATPase protein content, however it partially prevented the HS-induced loss of the Na,K-ATPase electrogenic activity and sarcolemma depolarization. These changes were associated with increased phosphorylation levels of AMP-activated protein kinase (AMPK), its substrate acetyl-CoA carboxylase and p70 protein, accompanied with increased mRNA expression of interleikin-6 (IL-6) and IL-6 receptor. Considering the role of AMPK in regulation of the Na,K-ATPase, we suggest an IL-6/AMPK contribution to prevent the effects of chronic ouabain under skeletal muscle disuse.

scholarly journals Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle

2015 ◽  
Vol 309 (3) ◽  
pp. R295-R303 ◽  
Author(s):  
Laelie A. Snook ◽  
Emery M. Nelson ◽  
David J. Dyck ◽  
David C. Wright ◽  
Graham P. Holloway
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Serum Insulin ◽  
Current Data ◽  
Signaling Mechanism ◽  
Akt Phosphorylation ◽  
Glucose Challenge ◽  
Muscle Glucose Transport

Several gastrointestinal proteins have been identified to have insulinotropic effects, including glucose-dependent insulinotropic polypeptide (GIP); however, the direct effects of incretins on skeletal muscle glucose transport remain largely unknown. Therefore, the purpose of the current study was to examine the role of GIP on skeletal muscle glucose transport and insulin signaling in rats. Relative to a glucose challenge, a mixed glucose+lipid oral challenge increased circulating GIP concentrations, skeletal muscle Akt phosphorylation, and improved glucose clearance by ∼35% ( P < 0.05). These responses occurred without alterations in serum insulin concentrations. In an incubated soleus muscle preparation, GIP directly stimulated glucose transport and increased GLUT4 accumulation on the plasma membrane in the absence of insulin. Moreover, the ability of GIP to stimulate glucose transport was mitigated by the addition of the PI 3-kinase (PI3K) inhibitor wortmannin, suggesting that signaling through PI3K is required for these responses. We also provide evidence that the combined stimulatory effects of GIP and insulin on soleus muscle glucose transport are additive. However, the specific GIP receptor antagonist (Pro3)GIP did not attenuate GIP-stimulated glucose transport, suggesting that GIP is not signaling through its classical receptor. Together, the current data provide evidence that GIP regulates skeletal muscle glucose transport; however, the exact signaling mechanism(s) remain unknown.

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