Muscle (Exam II) Flashcards
What is the distinction between a structural syncytium and a functional syncytium? Is skeletal muscle a structural or a functional syncytium? Cardiac muscle? Smooth muscle?
A structural syncytium (a “true” syncytium) is a multinucleated cell formed by the fusion of previously independent cells. Skeletal muscle is a structural syncytium since each mature cell is formed by the fusion of uninucleate myoblasts during development. The syncytiotrophoblast of the placenta is another example of a structural syncytium.
In contrast, a functional syncytium is a group of separate cells that function in a coordinated way, as if they were all part of one single cell. In order to do this they must be joined together by communicating junctions such as gap junctions that allow direct cell-to-cell passage of the ions and small signaling molecules that control the coordinated activity. A ciliated epithelium where the cilia beat in synchronous waves is a functional syncytium, as is cardiac muscle where the cells contract in a coordinated fashion.
In most locations in the body, smooth muscle cells are connected to one another by gap junctions to form a group of cells that function as a syncytium.
What specific name is given to the layer of connective tissue that immediately surrounds each muscle cell? Each fascicle (bundle) of muscle cells? An entire muscle?
The connective tissue that surrounds each individual muscle cells is the endomysium. It is composed mainly of fine reticular fibers. It contains small capillaries and nerve terminals. Perimysium is the connective tissue that surrounds groups of muscle cells and thus forms a bundle or fascicle of cells. It is best developed in skeletal muscle, but even there it is not always clearly evident. Nerve bundles and vessels larger than capillaries tend to travel in the perimysium. The connective tissue that surrounds an entire muscle is the epimysium. In gross anatomy the epimysium of a skeletal muscle would be called the investing fascia of the muscle. Epimysium is not well defined around cardiac or smooth muscle and the term is rarely used with reference to them.
What is the relationship between a myofibril, a sarcomere, and a myofilament?
The thick (myosin) and thin (actin) filaments are myofilaments. In striated muscle they are arranged to form the A band and I band of the sarcomeres.
The sarcomere is the functional unit of striated muscle extending between two adjacent Z-lines (A sarcomere would therefore extend from the mid-point of one I band to the mid-point of the next, with an A-band between). Many sarcomeres joined end-to-end form a myofibril. There are many myofibrils within the cytoplasm of a single skeletal or cardiac muscle cell.
Thus a myofilament is the smallest of the structures listed in this question. It takes many myofilaments to make a sarcomere, many sarcomeres to make a myofibril, and many myofibrils to fill the cytoplasm of a single muscle cell.
During contraction of skeletal or cardiac muscle, do the I bands shorten or remain constant in length? The A bands?
The I bands shorten as the thin filaments overlap more and more with the thick filaments of the A bands. An A band remains constant in length since its length is determined by the length of the thick filaments, which does not change.
Suppose you were looking at a cross section of a sarcomere by EM. If you saw only thick filaments, and these filaments appeared to be cross-linked to one another, you could conclude that this cross section had passed through what part of the sarcomere (Z line, I band, zone of thick-thin overlap in the A band, H zone, or M-line)?
This section passed through the M-line.
In the Z line or the I band you would see only thin filaments, not thick.
In the zone of overlap in the A band, there would be both thick and thin filaments.
In the H zone, there would be only thick filaments, but they would not be cross-connected.
Only in the M-line would you see cross-connected thick filaments and no thin filaments. The cross connections are formed by accessory proteins such as myomesin that hold the thick filaments in register with one another.
In skeletal and cardiac muscle, is the sarcoplasmic reticulum located between myofibrils or between neighboring muscle cells?
The sarcoplasmic reticulum is the equivalent of the smooth endoplasmic reticulum (SER) in skeletal and smooth muscle cells.
As is always the case with SER, it is located in the cytoplasm the cells rather than in the extracellular space between cells. In striated muscle it closely surrounds each of the myofibrils in the sarcoplasm.
The SER of any cell type has the ability to sequester calcium, but in skeletal and cardiac muscle this function is highly developed and essential to the process of contraction.
As a result, the SER in striated muscle is very extensive, has a particular form and arrangement relative to the myofibrils, and is given the special name “sarcoplasmic reticulum”
Into which type of junction in an intercalated disk do the actin filaments of cardiac muscle insert? This junction is analogous to what component of the junctional complexes that are found between epithelial cells?
The actin filaments of the I band in cardiac muscle insert into the fascia adherens of the intercalated disk. The fasciae adherentes are located on the transverse portions of each disk.
This type of junction is analogous to the zonula adherens of a junctional complex between epithelial cells, which also serves as an attachment site for actin filaments.
The two junctions also resemble one another when seen in thin sections, but differ in their 3-dimensional shape. The zonula adherens is a belt-like structure (zonula = belt in Latin) that runs completely around the epithelial cell near its apical end, binding it to all cells that border on it laterally. In contrast, the fascia adherens is a broad irregularly shaped plaque that unites the ends of two adjacent cardiac muscle cells.
Name two characteristic features visible by EM in smooth muscle that distinguish it from skeletal or cardiac muscle.
Two diagnostic features of smooth muscle cells in electron micrographs are dense bodies and caveolae.
- Dense bodies often appear to be small separate structures that are either associated with the plasma membrane or free in the cytosol, but they are actually elongated, branching structures that extend from the membrane throughout the cytoplasm. They are analogous in function to Z lines, in that actin filaments and other components of the cytoskeleton are anchored to them.
- Caveolae are numerous small vesicular invaginations of the plasma membrane that allow calcium to enter smooth muscle cells via calcium channels in their membrane. They are also involved in releasing calcium from nearby SER cisternae into the cytosol.
If you were looking at a cross section of the colon, would the individual smooth muscle cells of the inner circularly arranged muscle layer be cut longitudinally or in cross section?
They will be cut longitudinally, while the cells of the outer longitudinal layer will be cut in cross section. If you were looking at a longitudinal section through the colon rather than a cross section, the appearance of the muscle cells in the two layers would be reversed (cells of the inner circular layer cut in cross section, cells of the outer longitudinal layer cut longitudinally). The appearance of the cells depends on their orientation relative to the plane of section through the organ.
Skeletal Muscle Organization
Thick & thin myofilaments form a sarcomere Sarcomeres are arranged end-to-end form a myofibril Many myofibrils are arranged side by side in the cytoplasm of each skeletal muscle cell. A skeletal muscle cell is also called a muscle fiber Many muscle cells are bundled together by connective tissue (perimysium) to form a muscle fascicle. Many muscle fascicles are bundled together by connective tissue to form a single muscle
Summary: Myofilaments → Sarcomeres → Myofibrils → Cells (Fibers) → Fascicles → Muscles
Connective Tissue in Skeletal Muscle
- Endomysium: Loose connective tissue that surrounds individual muscle cells. Consists mainly of reticular fibers
- Perimysium: Dense irregular connective tissue that surrounds a muscle fascicle; contains the larger blood vessels
- Epimysium: Dense irregular connective tissue that surrounds an entire muscle (= the investing fascia of the muscle)
Development, growth and regeneration of muscle cells
Mesenchymal stem cells form myoblasts → Myoblasts cease dividing, fuse end to end to form myotubes. Immature myotubes have central nuclei. As contractile apparatus (myofilaments) and complex membrane structure (sarcoplasmic reticulum and t-tubules) develop, nuclei displaced to periphery.
Satellite cells represent persistent stem cells. They are found between muscle fibers and have single nucleus.
The Sarcomere
- Specialized smooth endoplasmic reticulum.
- Forms membranous meshwork around each myofibril. At junction of A and I bands, membrane dilates and flattens (terminal cisternae).
- Functions to sequester calcium between contractions (longitudinal portions) and allow its release in preparation release into the cytoplasm in preparation for contraction (at the terminal cisternae).
- Have ryanodine receptors = gated Ca2+ release channels
- It runs from one Z-line to the next and contains: an A band in the center of the sarcomere and half of an I band at each end of the sarcomere
I-Band of Sarcomere
- Light-staining band
- Contains the parts of thin filaments not overlapped by thick filaments
- Bisected by Z-line, which anchors the actin filaments
- Its length decreases during contraction
A-Band of Sarcomere (including H-zone, Bare zone, and M-line).
- Dark staining band of constant length
- Length corresponds to the length of the thick filaments
- Also contains the part of the thin filaments that overlaps the thick filaments.
- At EM level the A-band also contains:
- H-zone: Lighter staining region at center of A band Contains only thick filaments (i.e., is the region of the thick filaments that doesnʼt overlap with thin) Length changes during contraction
- Bare zone: An even lighter staining region within the H zone Contains shafts of thick filaments but no myosin heads Constant in length
- M-line: A darker line at the center of bare zone Site of cross-connections between thick filaments Constant in length
T-tubules in skeletal muscle
- Invaginations of sarcolemma into interior of cell.
- Extend transversely into muscle cell to surround individual myofibrils (at junction of A and I bands in mammalian skeletal muscle).
- Function to conduct nerve impulse into cell, transferring it to the terminal cisternae of sarcoplasmic reticulum
- Have dihydropyridine (DHP) receptors = depolarization-sensitive transmembrane channels organized into tetrads
Triad in skeletal muscle
- A T-tubule, together with a pair of terminal cisternae of the SR
- Located at A and I band junction in mammalian skeletal muscle.
- In muscles of some other vertebrates (i.e. amphibians), located at Z-line.
- Ryanodine and Dihydropyridine receptors closely opposed in the triad
- Site of excitation-contraction (EC) coupling
Skeletal Muscle Cells: description, nucleation, and structure.
- Mature fibers are long, unbranched, cylindrical cells
- Multinucleated, with peripheral nuclei
- Each cell is a syncytium formed by fusion of uninucleate cells (myoblasts)
Thick Filaments of skeletal muscle
- Each thick filament contains 200-300 myosin molecules.
- Each myosin molecule has elongated tail and globular head.
- Head region contains actin-binding site and ATP-binding site.
- Aggregate tail-to-tail forming central bare zone.
- Aggregate head to tail on each side of the bare zone.
- Held together by cross bands formed by Myomesin and C protein at midpoint of A band to form M-line.
- Thick filaments also held in place by a core of titin, an accessory protein that extends from M-line to Z-line.
Thin Filaments on the sarcomere
- Originate at Z-line
- Project towards center of two adjacent sarcomeres
- Constitute I band and extend some distance into A band
Thin Filaments (composition) of skeletal muscle
- Actin filaments are highly polarized with plus end binding to Z-line (via α-actinin) minus end extending to the M line.
- Nebulin runs the length of the thin filament and assists α-actinin in binding thin filament to Z-line
- Tropomyosin = long pencil shaped proteins form long filaments that run in grooves between F-actin molecules.
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Troponin, binds to tropomyosin. It has 3 subunits:
- TnT binds to tropomyosin
- TnC binds calcium
- TnI binds actin, thus inhibiting actin - myosin interaction.
- Length of filament likely regulated by nebulin in conjunction with capping protein called tropomodulin f. Linked to cell membrane and external lamina (equivalent to a basal lamina) by protein complex that includes dystrophin.
Clinical Correlation: Muscular Dystrophy
Muscular dystrophy is attributed to mutations of the genes that encode for proteins of the dystrophin-glycoprotein complex that links dystrophin to the cell membrane (via the extracellular matrix proteins laminin and agrin).
There are several forms of the disease, but all will lead to progressive muscle weakness and cell death.
Summary of Z-line proteins and structures
- α-actinin, assisted by nebulin, anchors thin filaments to the Z-line.
- Ends of titin proteins insert into Z-line, anchoring thick filaments.
- Intermediate filaments (e.g. desmin and vimentin), secure Z-lines in adjacent myofibrils.
- Near sarcolemma, Z-lines attached to inner aspect of membrane by aggregations of intermediate filaments and some microtubular structures
Neuromuscular Junctions (Motor Endplates)
- Terminations of motor neurons on skeletal muscle cells
- Neurons that innervate skeletal muscle cells are called somatic motor neurons The axon branches near its end (terminal arborization)
- NOTE: One neuron plus all the muscle cells innervated by it is known as a motor unit.
- Each muscle cell is innervated by one motor endplate
- Each axonal branch ends in a motor endplate
- Axon loses its myelin sheath at the motor endplate, but remains partially covered by a Schwann cell
- Endplate has many mitochondria in the axon terminal
- Releases acetylcholine (ACh) from round, clear synaptic vesicles into the synaptic cleft
- The motor endplate sits in a depression in the muscle cell sarcolemma called the primary synaptic cleft
- Secondary synaptic clefts are formed by junctional folds of the sarcolemma ACh receptors are located at the crests of the junctional folds
- Subneural clefts (secondary synaptic clefts) are the spaces created between junctional folds
- External lamina of muscle cell (equivalent to a basal lamina) extends into synaptic cleft & subneural clefts
- Acetylcholinesterase is localized in external lamina
Clinical Correlate: Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis, or ALS (commonly known as Lou Gehrig’s Disease) affects motor neurons in the brain and anterior horn of the spinal cord. It causes progressive loss of motor control. This results in grouped atrophy of muscle fibers, as motor units are successively deinnervated.