Non‐technical summary
Glucose is stored as glycogen in skeletal muscle. The importance of glycogen as a fuel during exercise has been recognized since the 1960s; however, little is known about the ...precise mechanism that relates skeletal muscle glycogen to muscle fatigue. We show that low muscle glycogen is associated with an impairment of muscle ability to release Ca2+, which is an important signal in the muscle activation. Thus, depletion of glycogen during prolonged, exhausting exercise may contribute to muscle fatigue by causing decreased Ca2+ release inside the muscle. These data provide indications of a signal that links energy utilization, i.e. muscle contraction, with the energy content in the muscle, thereby inhibiting a detrimental depletion of the muscle energy store.
Little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. The aim of the present study was to examine the effect of glycogen on sarcoplasmic reticulum (SR) function in the arm and leg muscles of elite cross‐country skiers (n= 10, 72 ± 2 ml kg−1 min−1) before, immediately after, and 4 h and 22 h after a fatiguing 1 h ski race. During the first 4 h recovery, skiers received either water or carbohydrate (CHO) and thereafter all received CHO‐enriched food. Immediately after the race, arm glycogen was reduced to 31 ± 4% and SR Ca2+ release rate decreased to 85 ± 2% of initial levels. Glycogen noticeably recovered after 4 h recovery with CHO (59 ± 5% initial) and the SR Ca2+ release rate returned to pre‐exercise levels. However, in the absence of CHO during the first 4 h recovery, glycogen and the SR Ca2+ release rate remained unchanged (29 ± 2% and 77 ± 8%, respectively), with both parameters becoming normal after the remaining 18 h recovery with CHO. Leg muscle glycogen decreased to a lesser extent (71 ± 10% initial), with no effects on the SR Ca2+ release rate. Interestingly, transmission electron microscopy (TEM) analysis revealed that the specific pool of intramyofibrillar glycogen, representing 10–15% of total glycogen, was highly significantly correlated with the SR Ca2+ release rate. These observations strongly indicate that low glycogen and especially intramyofibrillar glycogen, as suggested by TEM, modulate the SR Ca2+ release rate in highly trained subjects. Thus, low glycogen during exercise may contribute to fatigue by causing a decreased SR Ca2+ release rate.
Mammalian hibernation is composed of multiple episodes of torpor bout, separated by phases of interbout arousal. During torpor, the skeletal muscles of mammals are undoubtedly inactive, but it has ...been proven to mitigate disuse atrophy. While interbout arousal has been implicated in the prevention of muscle atrophy, the underlying mechanisms sustaining muscle contraction remain to be explored. In the present study, Daurian ground squirrels (Spermophilus dauricus) were divided into four groups: pre-hibernation (PRE), torpor (TOR), interbout arousal (IBA), and post-hibernation (POST). The contractile performance of slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL) was detected both in situ and in vitro. Concurrently, mitochondrial respiratory chain complex activity in these muscles was quantified. Our findings revealed that in situ contractile properties of both muscles, including force, power output, time duration, and force development/relaxation rates of twitch contraction, and force and power output of tetanic contraction declined in the TOR group compared to the PRE group, but improved in the IBA and POST groups. Fatigue resistance of muscles, determined by the power output of repetitive tetanic contractions in situ, decreased in the TOR group but recovered in the IBA and POST groups. In vitro studies demonstrated that tetanic contraction power output in isolated muscles increased with muscle temperature in both TOR and IBA groups. However, at the same temperature, power output was consistently lower in the TOR group compared to the IBA group. Moreover, the activity of the mitochondrial respiratory chain complex, especially Complexes I and II, decreased in the TOR group but showed recovery in the IBA and POST groups. These findings suggest that both the contractile performance and fatigue resistance of mammalian skeletal muscle are compromised during torpor but can be improved during interbout arousal and post-hibernation. The rebound in body temperature and rise in mitochondrial respiratory chain complex activity in skeletal muscle are involved in enhancing contractile performance and fatigue resistance. This study suggests that interbout arousal functions as a vital temporal interval during which skeletal muscles can transition from the inactivity induced by torpor to a state of restored contractile functionality. Thus, interbout arousal serves as a behavioral safeguard against disuse-induced damage to skeletal muscles during hibernation.
In skeletal muscle, nebulin stabilizes and regulates the length of thin filaments, but the underlying mechanism remains nebulous. In this work, we used cryo-electron tomography and subtomogram ...averaging to reveal structures of native nebulin bound to thin filaments within intact sarcomeres. This in situ reconstruction provided high-resolution details of the interaction between nebulin and actin, demonstrating the stabilizing role of nebulin. Myosin bound to the thin filaments exhibited different conformations of the neck domain, highlighting its inherent structural variability in muscle. Unexpectedly, nebulin did not interact with myosin or tropomyosin, but it did interact with a troponin T linker through two potential binding motifs on nebulin, explaining its regulatory role. Our structures support the role of nebulin as a thin filament "molecular ruler" and provide a molecular basis for studying nemaline myopathies.
Background
Regenerative peripheral nerve interfaces (RPNIs) transduce neural signals to provide high‐fidelity control of neuroprosthetic devices. Traditionally, rat RPNIs are constructed with ~150 mg ...of free skeletal muscle grafts. It is unknown whether larger free muscle grafts allow RPNIs to transduce greater signal.
Methods
RPNIs were constructed by securing skeletal muscle grafts of various masses (150, 300, 600, or 1200 mg) to the divided peroneal nerve. In the control group, the peroneal nerve was transected without repair. Endpoint assessments were conducted 3 mo postoperatively.
Results
Compound muscle action potentials (CMAPs), maximum tetanic isometric force, and specific muscle force were significantly higher for both the 150 and 300 mg RPNI groups compared to the 600 and 1200 mg RPNIs. Larger RPNI muscle groups contained central areas lacking regenerated muscle fibers.
Conclusions
Electrical signaling and tissue viability are optimal in smaller as opposed to larger RPNI constructs in a rat model.
Objectives
Chemical shift encoding-based water–fat MRI derived proton density fat fraction (PDFF) of the paraspinal muscles has been emerging as a surrogate marker in subjects with sarcopenia, lower ...back pain, injuries and neuromuscular disorders. The present study investigates the performance of paraspinal muscle PDFF and cross-sectional area (CSA) in predicting isometric muscle strength.
Methods
Twenty-six healthy subjects (57.7% women; age: 30 ± 6 years) underwent 3T axial MRI of the lumbar spine using a six-echo 3D spoiled gradient echo sequence for chemical shift encoding-based water–fat separation. Erector spinae and psoas muscles were segmented bilaterally from L2 level to L5 level to determine CSA and PDFF. Muscle flexion and extension maximum isometric torque values Nm at the back were measured with an isokinetic dynamometer.
Results
Significant correlations between CSA and muscle strength measurements were observed for erector spinae muscle CSA (r = 0.40;
p
= 0.044) and psoas muscle CSA (r = 0.61;
p
= 0.001) with relative flexion strength. Erector spinae muscle PDFF correlated significantly with relative muscle strength (extension: r = -0.51;
p
= 0.008; flexion: r = -0.54;
p
= 0.005). Erector spinae muscle PDFF, but not CSA, remained a statistically significant (
p
< 0.05) predictor of relative extensor strength in multivariate regression models (R
2
adj
= 0.34;
p
= 0.002).
Conclusions
PDFF measurements improved the prediction of paraspinal muscle strength beyond CSA. Therefore, chemical shift encoding-based water–fat MRI may be used to detect subtle changes in the paraspinal muscle composition.
Key Points
• We investigated the association of paraspinal muscle fat fraction based on chemical shift encoding-based water–fat MRI with isometric strength measurements in healthy subjects.
• Erector spinae muscle PDFF correlated significantly with relative muscle strength.
• PDFF measurements improved prediction of paraspinal muscle strength beyond CSA.
OBJECTIVESTo characterize muscle involvement and evaluate disease severity in patients with GNE myopathy using skeletal muscle MRI and proton magnetic resonance spectroscopy (H-MRS).
METHODSSkeletal ...muscle imaging of the lower extremities was performed in 31 patients with genetically confirmed GNE myopathy, including T1-weighted and STIR images, T1 and T2 mapping and H-MRS. Measures evaluated included longitudinal relaxation time (T1), transverse relaxation time (T2), and H-MRS fat fraction (FF). Thigh muscle volume was correlated with relevant measures of strength, function, and patient-reported outcomes.
RESULTSThe cohort was representative of a wide range of disease progression. Contractile thigh muscle volume ranged from 5.51% to 62.95%, and correlated with thigh strength (r = 0.91), the 6-minute walk test (r = 0.82), the adult myopathy assessment tool (r = 0.83), the activities-specific balance confidence scale (r = 0.65), and the inclusion body myositis functional rating scale (r = 0.62). Four stages of muscle involvement were distinguished by qualitative (T1W and STIR images) and quantitative methodsstage I) Unaffected muscle (T1 = 1,033 ± 74.2 ms, T2 = 40.0 ± 1.9 ms, FF = 7.4 ± 3.5%); Stage II) STIR hyperintense muscle with minimal or no fat infiltration (T1 = 1,305 ± 147 ms, T2 = 50.2 ± 3.5 ms, FF = 27.6 ± 12.7%); Stage III) Fat infiltration and STIR hyperintensity (T1 = 1,209 ± 348 ms, T2 = 73.3 ± 12.6 ms, FF = 57.5 ± 10.6%); and Stage IV) Complete fat replacement (T1 = 318 ± 39.9 ms, T2 = 114 ± 21.2 ms, FF = 85.6 ± 4.2%). H-MRS showed a significant decrease in intramyocellular lipid and trimethylamines (TMA) between stage I and II, suggesting altered muscle metabolism at early stages.
CONCLUSIONMRI biomarkers can monitor muscle involvement and determine disease severity non-invasively in patients with GNE myopathy.
CLINICALTRIALS.GOV IDENTIFIERNCT01417533.
PDF
