scholarly journals Biomechanical Properties of the Sarcolemma and Costameres of Skeletal Muscle Lacking Desmin

2021 ◽  
Vol 12 ◽  
Author(s):  
Karla P. Garcia-Pelagio ◽  
Robert J. Bloch
Keyword(s):  
Skeletal Muscle ◽  
Lateral Force ◽  
Biomechanical Properties ◽  
Contractile Force ◽  
Contractile Apparatus ◽  
Force Transmission ◽  
Fast Twitch Muscle ◽  
Intracellular Organelles ◽  
Time Required ◽  
Fast Twitch

Intermediate filaments (IFs), composed primarily by desmin and keratins, link the myofibrils to each other, to intracellular organelles, and to the sarcolemma. There they may play an important role in transfer of contractile force from the Z-disks and M-lines of neighboring myofibrils to costameres at the membrane, across the membrane to the extracellular matrix, and ultimately to the tendon (“lateral force transmission”). We measured the elasticity of the sarcolemma and the connections it makes at costameres with the underlying contractile apparatus of individual fast twitch muscle fibers of desmin-null mice. By positioning a suction pipet to the surface of the sarcolemma and applying increasing pressure, we determined the pressure at which the sarcolemma separated from nearby sarcomeres, Pseparation, and the pressure at which the isolated sarcolemma burst, Pbursting. We also examined the time required for the intact sarcolemma-costamere-sarcomere complex to reach equilibrium at lower pressures. All measurements showed the desmin-null fibers to have slower equilibrium times and lower Pseparation and Pbursting than controls, suggesting that the sarcolemma and its costameric links to nearby contractile structures were weaker in the absence of desmin. Comparisons to earlier values determined for muscles lacking dystrophin or synemin suggest that the desmin-null phenotype is more stable than the former and less stable than the latter. Our results are consistent with the moderate myopathy seen in desmin-null muscles and support the idea that desmin contributes significantly to sarcolemmal stability and lateral force transmission.

scholarly journals Osteocytic Connexin43 Channels Regulate Bone–Muscle Crosstalk

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 237
Author(s):  
Guobin Li ◽  
Lan Zhang ◽  
Kaiting Ning ◽  
Baoqiang Yang ◽  
Francisca M. Acosta ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Transgenic Mice ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Contractile Force ◽  
Fast Twitch Muscle ◽  
And Function ◽  
Fast Twitch ◽  
Muscle Contractile

Bone–muscle crosstalk plays an important role in skeletal biomechanical function, the progression of numerous pathological conditions, and the modulation of local and distant cellular environments. Previous work has revealed that the deletion of connexin (Cx) 43 in osteoblasts, and consequently, osteocytes, indirectly compromises skeletal muscle formation and function. However, the respective roles of Cx43-formed gap junction channels (GJs) and hemichannels (HCs) in the bone–muscle crosstalk are poorly understood. To this end, we used two Cx43 osteocyte-specific transgenic mouse models expressing dominant negative mutants, Δ130–136 (GJs and HCs functions are inhibited), and R76W (only GJs function is blocked), to determine the effect of these two types of Cx43 channels on neighboring skeletal muscle. Blockage of osteocyte Cx43 GJs and HCs in Δ130–136 mice decreased fast-twitch muscle mass with reduced muscle protein synthesis and increased muscle protein degradation. Both R76W and Δ130–136 mice exhibited decreased muscle contractile force accompanied by a fast-to-slow fiber transition in typically fast-twitch muscles. In vitro results further showed that myotube formation of C2C12 myoblasts was inhibited after treatment with the primary osteocyte conditioned media (PO CM) from R76W and Δ130–136 mice. Additionally, prostaglandin E2 (PGE2) level was significantly reduced in both the circulation and PO CM of the transgenic mice. Interestingly, the injection of PGE2 to the transgenic mice rescued fast-twitch muscle mass and function; however, this had little effect on protein synthesis and degradation. These findings indicate a channel-specific response: inhibition of osteocytic Cx43 HCs decreases fast-twitch skeletal muscle mass alongside reduced protein synthesis and increased protein degradation. In contrast, blockage of Cx43 GJs results in decreased fast-twitch skeletal muscle contractile force and myogenesis, with PGE2 partially accounting for the measured differences.

Alpha-actin and cytochrome c mRNAs in atrophied adult rat skeletal muscle

1988 ◽  
Vol 254 (5) ◽  
pp. C651-C656 ◽  
Author(s):  
P. Babij ◽  
F. W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Muscle Atrophy ◽  
Weight Bearing ◽  
Skeletal Muscle Atrophy ◽  
Rna Content ◽  
Mrna Content ◽  
Fast Twitch Muscle ◽  
Alpha Actin ◽  
Fast Twitch

Specific complementary DNA (cDNA) hybridization probes were used to estimate the levels of alpha-actin and cytochrome c mRNAs and also 18S rRNA in three models of skeletal muscle atrophy. After 7 days of hindlimb suspension, or immobilization, or denervation, protein content decreased 26-32% in all muscles studied except suspended fast-twitch muscle, which lost only half as much protein. alpha-Actin mRNA content decreased 51-66% and cytochrome c mRNA content decreased 42-61% in slow- and fast-twitch muscles in all three models of atrophy. However, total RNA content did not show similar directional changes; RNA content decreased 27-44% in suspended and immobilized muscle but was unchanged in denervated fast-twitch muscle. The results were interpreted to suggest that loss of weight-bearing function of skeletal muscle is a major factor affecting the levels of alpha-actin and cytochrome c mRNAs during muscle atrophy.

Dynamics and Consequences of Potassium Shifts in Skeletal Muscle and Heart During Exercise

2000 ◽  
Vol 80 (4) ◽  
pp. 1411-1481 ◽  
Author(s):  
Ole M. Sejersted ◽  
Gisela Sjøgaard
Keyword(s):  
Skeletal Muscle ◽  
Force Production ◽  
Membrane Conductance ◽  
Cell Swelling ◽  
Modifying Factors ◽  
Fast Twitch Muscle ◽  
T Tubules ◽  
Exercise Induced ◽  
Fast Twitch ◽  
Muscle Excitability

Since it became clear that K+shifts with exercise are extensive and can cause more than a doubling of the extracellular [K+] ([K+]s) as reviewed here, it has been suggested that these shifts may cause fatigue through the effect on muscle excitability and action potentials (AP). The cause of the K+shifts is a transient or long-lasting mismatch between outward repolarizing K+currents and K+influx carried by the Na+-K+pump. Several factors modify the effect of raised [K+]sduring exercise on membrane potential ( Em) and force production. 1) Membrane conductance to K+is variable and controlled by various K+channels. Low relative K+conductance will reduce the contribution of [K+]sto the Em. In addition, high Cl−conductance may stabilize the Emduring brief periods of large K+shifts. 2) The Na+-K+pump contributes with a hyperpolarizing current. 3) Cell swelling accompanies muscle contractions especially in fast-twitch muscle, although little in the heart. This will contribute considerably to the lowering of intracellular [K+] ([K+]c) and will attenuate the exercise-induced rise of intracellular [Na+] ([Na+]c). 4) The rise of [Na+]cis sufficient to activate the Na+-K+pump to completely compensate increased K+release in the heart, yet not in skeletal muscle. In skeletal muscle there is strong evidence for control of pump activity not only through hormones, but through a hitherto unidentified mechanism. 5) Ionic shifts within the skeletal muscle t tubules and in the heart in extracellular clefts may markedly affect excitation-contraction coupling. 6) Age and state of training together with nutritional state modify muscle K+content and the abundance of Na+-K+pumps. We conclude that despite modifying factors coming into play during muscle activity, the K+shifts with high-intensity exercise may contribute substantially to fatigue in skeletal muscle, whereas in the heart, except during ischemia, the K+balance is controlled much more effectively.

scholarly journals S-Glutathionylation of troponin I (fast) increases contractile apparatus Ca2+sensitivity in fast-twitch muscle fibres of rats and humans

2012 ◽  
Vol 590 (6) ◽  
pp. 1443-1463 ◽  
Author(s):  
J. P. Mollica ◽  
T. L. Dutka ◽  
T. L. Merry ◽  
C. R. Lamboley ◽  
G. K. McConell ◽  
...  
Keyword(s):  
Troponin I ◽  
Muscle Fibres ◽  
Contractile Apparatus ◽  
Fast Twitch Muscle ◽  
Fast Twitch

scholarly journals Insulin-sensitive regulation of glucose transport and GLUT4 translocation in skeletal muscle of GLUT1 transgenic mice

1998 ◽  
Vol 337 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Garret J. ETGEN ◽  
William J. ZAVADOSKI ◽  
Geoffrey D. HOLMAN ◽  
E. Michael GIBBS
Keyword(s):  
Skeletal Muscle ◽  
Cell Surface ◽  
Transgenic Mice ◽  
Glucose Transport ◽  
Hind Limb ◽  
Glucose Transporter ◽  
Glut4 Translocation ◽  
Transport Activity ◽  
Fast Twitch Muscle ◽  
Fast Twitch

Skeletal muscle glucose transport was examined in transgenic mice overexpressing the glucose transporter GLUT1 using both the isolated incubated-muscle preparation and the hind-limb perfusion technique. In the absence of insulin, 2-deoxy-d-glucose uptake was increased ∼ 3–8-fold in isolated fast-twitch muscles of GLUT1 transgenic mice compared with non-transgenic siblings. Similarly, basal glucose transport activity was increased ∼ 4–14-fold in perfused fast-twitch muscles of transgenic mice. In non-transgenic mice insulin accelerated glucose transport activity ∼ 2–3-fold in isolated muscles and to a much greater extent (∼ 7–20-fold) in perfused hind-limb preparations. The observed effect of insulin on glucose transport in transgenic muscle was similarly dependent upon the technique used for measurement, as insulin had no effect on isolated fast-twitch muscle from transgenic mice, but significantly enhanced glucose transport in perfused fast-twitch muscle from transgenic mice to ∼ 50–75% of the magnitude of the increase observed in non-transgenic mice. Cell-surface glucose transporter content was assessed via 2-N-4-(l-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(d -mannos-4-yloxy)-2-propylamine photolabelling methodology in both isolated and perfused extensor digitorum longus (EDL). Cell-surface GLUT1 was enhanced by as much as 70-fold in both isolated and perfused EDL of transgenic mice. Insulin did not alter cell-surface GLUT1 in either transgenic or non-transgenic mice. Basal levels of cell-surface GLUT4, measured in either isolated or perfused EDL, were similar in transgenic and non-transgenic mice. Interestingly, insulin enhanced cell-surface GLUT4 ∼ 2-fold in isolated EDL and ∼ 6-fold in perfused EDL of both transgenic and non-transgenic mice. In summary, these results reveal differences between isolated muscle and perfused hind-limb techniques, with the latter method showing a more robust responsiveness to insulin. Furthermore, the results demonstrate that muscle overexpressing GLUT1 has normal insulin-induced GLUT4 translocation and the ability to augment glucose-transport activity above the elevated basal rates.

scholarly journals Actin scaffolding by clathrin heavy chain is required for skeletal muscle sarcomere organization

2014 ◽  
Vol 205 (3) ◽  
pp. 377-393 ◽  
Author(s):  
Stéphane Vassilopoulos ◽  
Christel Gentil ◽  
Jeanne Lainé ◽  
Pierre-Olivier Buclez ◽  
Agathe Franck ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heavy Chain ◽  
Neuromuscular Disorders ◽  
Contractile Force ◽  
Contractile Apparatus ◽  
Intracellular Membrane ◽  
Clathrin Heavy Chain ◽  
Attachment Sites ◽  
Main Component

The ubiquitous clathrin heavy chain (CHC), the main component of clathrin-coated vesicles, is well characterized for its role in intracellular membrane traffic and endocytosis from the plasma membrane (PM). Here, we demonstrate that in skeletal muscle CHC regulates the formation and maintenance of PM–sarcomere attachment sites also known as costameres. We show that clathrin forms large coated lattices associated with actin filaments and the muscle-specific isoform of α-actinin at the PM of differentiated myotubes. Depletion of CHC in myotubes induced a loss of actin and α-actinin sarcomeric organization, whereas CHC depletion in vivo induced a loss of contractile force due to the detachment of sarcomeres from the PM. Our results suggest that CHC contributes to the formation and maintenance of the contractile apparatus through interactions with costameric proteins and highlight an unconventional role for CHC in skeletal muscle that may be relevant to pathophysiology of neuromuscular disorders.

scholarly journals Syncoilin is required for generating maximum isometric stress in skeletal muscle but dispensable for muscle cytoarchitecture

2008 ◽  
Vol 294 (5) ◽  
pp. C1175-C1182 ◽  
Author(s):  
Jianlin Zhang ◽  
Marie-Louise Bang ◽  
David S. Gokhin ◽  
Yingchun Lu ◽  
Li Cui ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Striated Muscle ◽  
Neuromuscular Diseases ◽  
Eccentric Contraction ◽  
Lateral Force ◽  
Force Transmission ◽  
Skeletal Muscle Contraction ◽  
Supportive Role

Syncoilin is a striated muscle-specific intermediate filament-like protein, which is part of the dystrophin-associated protein complex (DPC) at the sarcolemma and provides a link between the extracellular matrix and the cytoskeleton through its interaction with α-dystrobrevin and desmin. Its upregulation in various neuromuscular diseases suggests that syncoilin may play a role in human myopathies. To study the functional role of syncoilin in cardiac and skeletal muscle in vivo, we generated syncoilin-deficient ( syncoilin−/−) mice. Our detailed analysis of these mice up to 2 yr of age revealed that syncoilin is entirely dispensable for cardiac and skeletal muscle development and maintenance of cellular structure but is required for efficient lateral force transmission during skeletal muscle contraction. Notably, syncoilin−/− skeletal muscle generates less maximal isometric stress than wild-type (WT) muscle but is as equally susceptible to eccentric contraction-induced injury as WT muscle. This suggests that syncoilin may play a supportive role for desmin in the efficient coupling of mechanical stress between the myofibril and fiber exterior. It is possible that the reduction in isometric stress production may predispose the syncoilin skeletal muscle to a dystrophic condition.

Prolonged contraction-relaxation cycle of fast-twitch muscles in parvalbumin knockout mice

1999 ◽  
Vol 276 (2) ◽  
pp. C395-C403 ◽  
Author(s):  
B. Schwaller ◽  
J. Dick ◽  
G. Dhoot ◽  
S. Carroll ◽  
G. Vrbova ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Calcium Binding ◽  
Muscle Fibers ◽  
Relaxation Cycle ◽  
Single Twitch ◽  
Intracellular Ca ◽  
Fast Twitch Muscle ◽  
High Concentrations ◽  
Time Required ◽  
Fast Twitch

The calcium-binding protein parvalbumin (PV) occurs at high concentrations in fast-contracting vertebrate muscle fibers. Its putative role in facilitating the rapid relaxation of mammalian fast-twitch muscle fibers by acting as a temporary buffer for Ca2+ is still controversial. We generated knockout mice for PV (PV −/−) and compared the Ca2+ transients and the dynamics of contraction of their muscles with those from heterozygous (PV +/−) and wild-type (WT) mice. In the muscles of PV-deficient mice, the decay of intracellular Ca2+ concentration ([Ca2+]i) after 20-ms stimulation was slower compared with WT mice and led to a prolongation of the time required to attain peak twitch tension and to an extension of the half-relaxation time. The integral [Ca2+]iin muscle fibers of PV −/− mice was higher and consequently the force generated during a single twitch was ∼40% greater than in PV +/− and WT animals. Acceleration of the contraction-relaxation cycle of fast-twitch muscle fibers by PV may confer an advantage in the performance of rapid, phasic movements.

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