The striations are created by the organization of actin and myosin resulting in the banding pattern of myofibrils.
Watch this video to learn more about what happens at the neuromuscular junction. Can you give an example of each? A small motor has one neuron supplying few skeletal muscle fibers for very fine movements, like the extraocular eye muscles, where six fibers are supplied by one neuron. Muscles would lose their integrity during powerful movements, resulting in muscle damage.
When a muscle contracts, the force of movement is transmitted through the tendon, which pulls on the bone to produce skeletal movement. Produce movement of the skeleton, maintain posture and body position, support soft tissues, encircle openings of the digestive, urinary, and other tracts, and maintain body temperature.
What are the opposite roles of voltage-gated sodium channels and voltage-gated potassium channels? Skip to content Muscle Tissue. Learning Objectives By the end of this section, you will be able to: Describe the layers of connective tissues packaging skeletal muscle Explain how muscles work with tendons to move the body Identify areas of the skeletal muscle fibers Describe excitation-contraction coupling.
The Three Connective Tissue Layers. Bundles of muscle fibers, called fascicles, are covered by the perimysium. Muscle fibers are covered by the endomysium. Skeletal Muscle Fibers Because skeletal muscle cells are long and cylindrical, they are commonly referred to as muscle fibers. Muscle Fiber. A skeletal muscle fiber is surrounded by a plasma membrane called the sarcolemma, which contains sarcoplasm, the cytoplasm of muscle cells. A muscle fiber is composed of many fibrils, which give the cell its striated appearance.
The sarcomere, the region from one Z-line to the next Z-line, is the functional unit of a skeletal muscle fiber. Excitation-Contraction Coupling All living cells have membrane potentials, or electrical gradients across their membranes. Motor End-Plate and Innervation. The motor end-plate is the location of the ACh-receptors in the muscle fiber sarcolemma.
When ACh molecules are released, they diffuse across a minute space called the synaptic cleft and bind to the receptors. Narrow T-tubules permit the conduction of electrical impulses. The SR functions to regulate intracellular levels of calcium. Chapter Review Skeletal muscles contain connective tissue, blood vessels, and nerves.
Interactive Link Questions Watch this video to learn more about macro- and microstructures of skeletal muscles. Critical Thinking Questions What would happen to skeletal muscle if the epimysium were destroyed? Describe how tendons facilitate body movement. Finally, the newly formed SR engages couplings at the A-I interface with the T-tubule originating from the sarcolemma. The molecular determinants implicated in the functional and structural organization of the SR have been reviewed elsewhere [ 16 ].
The chronology of SR biogenesis was well investigated using electron microscopy EM during muscle differentiation in mouse [ 17 ]. These observations were also supported by studies employing chicken embryo [ 18 ]. In mouse, the SR is detected from as early as embryonic day 14 E14 with punctate RyR clusters that are located in the periphery of the myofiber [ 17 ].
At this stage, the content of the feet RyR in the junctional SR is poor, and some SR elements without any feet are observed. At E16, RyR containing elements become abundant and start to be associated with the edges of A bands A-I junctions of the newly formed sarcomeres. This association results in a distinct banding pattern of a discrete SR network at the I-band with thin longitudinal connecting SR elements [ 17 ].
During the next days E17 and E18 , junctional SR acquires a predominant transverse distribution taking their final position by forming triad rows at each side of the Z-line two SR sacs connecting one T-tubule in each triad [ 17 ].
During the maturation of SR membranes, the frequency of feet increases, in particular, between E16 and E18, when all junctions become filled by feet.
The width of the junctional gap is between 9 and 12 nm. The maturation of the RyR containing elements is accomplished at birth [ 17 ]. Elegant experiments using tagged SR proteins in differentiating myotubes showed that the SR organization was paralleled by a dynamic localization of longitudinal and junctional SR proteins [ 19 ].
T-tubules are invaginations of the plasma membrane, which are present exclusively in striated muscle. Their role is to maintain the SR calcium store under the tight control of membrane depolarization via the voltage sensor channel DHPR [ 2 ]. Morphological studies in chicken and mouse embryos have revealed that the T-tubules start their formation after the SR [ 17 , 18 ].
In mouse embryos, the first defined tubules can be observed at E At this stage they take the aspect of short cylinders invaginating from the sarcolemma within the myotubes [ 17 ]. At E16, the newly formed T-tubules extend deeper within the myofiber, maintaining a connection with the surface by short transverse segments however they stay predominantly longitudinal.
During the last days of gestation E17, 18, 19 , T-tubules progressively invade the entire fiber; the majority of them are longitudinal with some transverse connecting elements [ 17 , 18 ]. The transverse orientation of T-tubules is achieved during the postnatal period. Final maturation of T-tubules is completed in mouse 3 weeks after birth [ 17 , 20 ].
Although the events characterizing T-tubule biogenesis and triad formation are morphologically defined, molecular mechanisms remain elusive. In this context, one should distinguish between mechanisms leading to T-tubule biogenesis and those involved in the proper assembling of triad components i. Proteins implicated in triad organization, roles and associated human diseases a.
Caveolae are subcompartments of the plasma membrane which take the aspect of nm vesicular invaginations, and have an important role in signal transduction and vesicular transport [ 21 ]. In contrast to the other plasma membrane regions which are composed mainly of phospholipids, caveolae are considered as cholesterol-sphingolipid rich raft domains [ 22 ].
The principal protein components of the caveolae are the caveolins CAV , which are cholesterol-binding proteins [ 22 ]. The caveolin family is represented in mammals by three members; both CAV1 and CAV2 are co-expressed in non-muscle cells especially adipocytes [ 21 , 23 ] whereas CAV3 is found essentially in striated muscles, and its expression is induced during muscle differentiation [ 24 ]. In skeletal muscle, CAV3 localizes at the sarcolemma where it can form a complex with dystrophin and its associated glycoproteins [ 25 ].
In addition to the sarcolemma, CAV3 is localized to the developing T-tubules [ 26 ]. Mutations within CAV3 are associated with several muscular disorders. In addition, CAV3 is found mutated in rippling muscle disease [ 28 ], familial hypertrophic cardiomyopathy [ 29 ] and long QT syndrome 9 [ 30 ].
Moreover, its expression is increased in tibialis anterior from the mdx mouse, suggesting that CAV3 may contribute to the pathogenesis of DMD [ 31 ]. Mice lacking CAV3 display a mild myopathic phenotype similar to the human pathology [ 32 ]. Besides, the ectopic expression of CAV3 in mice leads to Duchenne-like muscular dystrophic phenotype [ 33 ]. This provides evidence that CAV3 is crucial for muscle function and has a role in T-tubules biogenesis.
Several evidences lead to the hypothesis that similar mechanisms control the formation of the T-tubule system and the caveolae. Indeed, the mature and the developing T-tubules are associated with CAV3 and contain approximately four times more cholesterol than the plasma membrane [ 34 , 35 ]. Moreover, treatment of epithelial cells with Amphotericin B, a cholesterol-binding drug, results in a loss of morphologically defined caveolae at the cell surface.
Interestingly, other cholesterol-rich compartments such as the trans-Golgi network do not seem affected [ 34 ]. Proteins implicated in triad organization in skeletal muscle. Note that dyads are localized in proximity to the Z-line similar to vertebrate.
The Journal of Cell Biology, , Mutations in BIN1 are associated to the autosomal recessive form of centronuclear myopathy [ 36 ], a disease characterized by muscle weakness, myofiber atrophy, and abnormal positioning of nuclei within muscle fibers.
The ubiquitous amphiphysin 2, encoded by the BIN1 gene, is highly expressed in skeletal muscle and is proposed to participate in T-tubule biogenesis. Its role in this process is provided by a polybasic amino-acid stretch encoded by exon 11, which is important for its recruitment to T-tubule membranes [ 37 , 38 ].
In addition, BIN1 can tubulate membranes separately or in cooperation with dynamin 2 DNM2 , another protein mutated in centronuclear myopathy [ 40 , 41 ]. However, this interaction may not occur prior to BIN1 association to membranes, as the polybasic sequence binds to the SH3 domain when it is not membrane bound [ 42 ]. While the existence of this intramolecular regulation has been deciphered in cultured cells, it is not determined whether a similar mechanism regulates T-tubules curvature.
Nevertheless, myotubes expressing a BIN1 mutant lacking the polybasic sequence failed to form a normal membrane tubules network [ 42 ]. A drosophila mutant lacking the orthologue of BIN1 amphiphysin exhibits a skeletal muscle defect associated to alterations in T-tubule morphology and EC coupling Figure 3c-f [ 43 ].
Interestingly, EM analysis of muscle biopsies from patients with BIN1 mutations revealed abnormal morphology of T-tubules [ 44 ]. In cultured COS-1 cells, overexpression of a mutation related to CNM in the BAR domain failed to form membrane tubules compared to the wild-type construct, suggesting that the lack of BIN1-mediated membrane remodeling could be at the basis of the muscle disease [ 36 ].
However, these mice are dying perinatally due to cardiomyopathy, precluding a detailed analysis of skeletal muscle after birth [ 45 ]. It contains a C-terminal transmembrane domain and multiple C2 domains implicated in calcium binding and calcium-dependent membrane fusion and repair. Mutations within the DYSF gene are associated with allelic muscular disorders including autosomal recessive limb-girdle muscular dystrophy type 2B [ 46 ], Miyoshi myopathy [ 47 ], and distal anterior compartment myopathy [ 48 ].
DYSF has a sarcolemmal localization in differentiated skeletal muscle, which is related to its role in membrane repair [ 49 ].
However, studies performed in C2C12 cells have shown that during myotubes differentiation, DYSF is associated to the T-tubules network in addition to sites of cells fusion, and can translocate to the sarcolemma upon myofiber injury [ 50 ]. Interestingly, studies performed in adult rat muscles, in which regeneration was induced by subcutaneous injection of notexin, have revealed that during early stage of muscle fiber regeneration within the first week after notexin treatment , DYSF is mainly localized to T-tubules and translocates toward the sarcolemma in later stages of regeneration [ 51 ].
Several mouse lines have been generated to manipulate the level and the function of DYSF, and the spontaneous SJL strain was shown to encompass an in-frame deletion in the C-terminal of the Dysf gene [ 49 , 52 - 55 ].
Similarly to CAV3 mouse mutants, mice deficient for DYSF display alterations in T-tubule structure, with more dilated and longitudinally oriented tubules [ 51 ] Figure 3m-n. These defects are considered as primary, as they are observed at early stage of the disease when abnormalities in the myofibrillar architecture and the sarcolemma are minimal.
This hypothesis is also supported by the accumulation of subsarcolemmal vacuoles contiguous with the T-tubule system in dysferlinopathy patients [ 58 ]. In addition to the proteins mentioned above, which are involved in the biogenesis of T-tubules, other proteins are implicated in the maturation of SR terminal cisternae, and the junction between T-tubules and SR.
This is the case of members of the Synaptophysin family such as mitsugumin 29 MG29 or synaptophysin-like 2, SYPL2 , a transmembrane proteins highly enriched in heavy SR vesicles preparation [ 59 ].
MG29 is expressed early during myogenesis, even before the apparition of triads. It first associates to newly formed SR vesicles and then to triads, which appear later during myogenesis [ 59 ]. These observations implicate MG29 in the early formation of junctional SR and its connection to T-tubules [ 59 , 60 ]. In MG29 -KO mice, decreased muscle mass and a slight decrease in the force generation capacity were observed [ 61 ].
Dysfunction of store-operated calcium entry SOCE leading to defects in intracellular calcium homeostasis, and increased muscle fatigability were also reported in these mice [ 62 , 63 ]. EM analysis of mutant muscles revealed morphological alterations in triad structures, including a swollen SR and longitudinal T-tubules Figure 3g-j [ 61 ].
However, the actual association between SR and T-tubules does not appear altered. It thus remains unclear whether such disorders in the triad structure have a link with the observed defect in SOCE. Another mitsugumin, MG53 also called TRIM72 , has been identified as a key player in intracellular membrane trafficking and membrane repair machinery in striated muscles [ 64 , 65 ]. In addition to it specific expression in striated muscles, MG53 was shown to bind to dysferlin and caveolin 3, two proteins directly implicated in T-tubule biogenesis [ 64 , 66 ].
There are no studies demonstrating a direct implication of MG53 in the biogenesis of triad membranes; however, the current evidences sustain its implication as a potential new partner in this mechanism. More specifically, the N-terminal domain can bind to membrane phospholipids including sphingomyelin and phosphatidylcholine [ 67 ].
If the nerve supply to a muscle is destroyed, for example in an accident, its muscle fibres are no longer stimulated to contract in this way. This will cause the muscle to lose its tone and become flaccid. Eventually the muscle will start to waste away. What is Triad system? In the histology of skeletal muscle, a triad is the structure formed by a T tubule with a sarcoplasmic reticulum SR known as the terminal cisterna on either side.
What are T tubules made of? T-tubules are tubules formed from the same phospholipid bilayer as the surface membrane or sarcolemma of skeletal or cardiac muscle cells. What three structures make up a triad? A The triad is a structure formed by the interface between the T-tubule and 2 portions of the sarcoplasmic reticulum SR. It is normally seen on electron microscopy of longitudinal sections as a triplet of structures arrows between myo- fibrils and slightly offset from the Z-line.
What is a bundle of muscle fibers called? Each compartment contains a bundle of muscle fibers. Curtis BM, Catterall WA: Purification of the calcium antagonist receptor of the voltage-sensitive calcium channel from skeletal muscle transverse tubules.
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Takekura H, Franzini-Armstrong C: Correct targeting of dihydropyridine receptors and triadin in dyspedic mouse skeletal muscle in vivo. J Physiol. Marieb Elaine: Human Anatomy and Physiology. Google Scholar. Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Jocelyn Laporte. This article is published under license to BioMed Central Ltd.
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