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What are the connective tissue investment of skeletal muscles?
- Epimysium surrounds an entire muscle and forms aponeuroses, which connect skeletal muscle to muscle, and tendons, which connect and skeletal muscle to bone.
- Perimysium surrounds fascicles (small bundles) of muscle cells.
- Endomysium surrounds individual muscle cells and is composed of reticular fibers and an external lamina
A change in ...............can change a fiber's type.
What are the features of Type 2 muscles?
Low Mb, High ATPase and phosphorylase, few mitochondria, fast, anaerobic glycolysis, low lipid, high glycogen, easily fatigued
.............forms deep tubular invaginations, or T (transverse) tubules
Skeletal muscle cells possess cylindrical collections of ..............., 1 to 2 µm in diameter, which extend the entire length of the cell.
What are the features of myofibrils?
- 1) Composed of longitudinally arranged, cylindrical bundles of thick and thin myofilaments2) Precise alignment of myofibrils results in a characteristic banding pattern visible by light microscopy as alternating dark A bands and light I bands; the latter are bisected by Z disks
- 3)Myofibrils are held in alignment by the intermediate filament desmin (and during embryonic development also vimentin), assisted by plectin, which tethers Z disks of adjacent myofibrils to one another.
- 4) Desmin has also been shown to connect the cytoskeleton, nucleus, motor end plates, and mitochondria to the myofibrils, and in this fashion distribute the force of contraction throughout the entire cell, protecting the structural integrity of the muscle fiber
What are the features of Desmin related myopathy?
- Disorganized myofilaments and skeletal muscle fibers.
- Begin as progressive weakness in the muscles of the legs, followed by weakness in the trunk and the rest of the body.
- Because DRM affects cardiac and smooth muscles also, respiratory insufficiency, heart failure, and gastrointestinal functions follow with possibly fatal consequences
...................distribute the force of contraction throughout the entire cell, protecting the structural integrity of the muscle fiber
What is sarcomere?
The sarcomere is the regular repeating region between successive Z disks and constitutes the functional unit of contraction in skeletal muscle.
The .......forms a pair of dilated terminal cisternae, which encircle the myofibrils at the junction of each A and I band
What are the features of SR?
- Modified smooth endoplasmic reticulum (SER) that surrounds myofilaments and forms a meshwork around each myofibril.
- Forms a pair of dilated terminal cisternae, which encircle the myofibrils at the junction of each A and I band.
- It regulates muscle contraction by sequestering calcium ions (leading to relaxation) or releasing calcium ions (leading to contraction).
What are triads in skeletal muscles?
- Triads are specialized complexes consisting of a narrow central T tubule flanked on each side by terminal cisternae of the SR.
- They are located at the A–I junction in mammalian skeletal muscle cells and help provide uniform contraction throughout the muscle cell.
Which structure help provide uniform contraction throughout the muscle cell?
What are satellite cells?
Satellite cells (myoblastlike cells that probably are left over from embryonic development) lie within the external lamina (basal lamina) of skeletal muscle cells. These regenerative cells differentiate, fuse with one another, and form skeletal muscle cells when the need arises
In order to ensure that a muscle cell does not become overly long or broad, muscle cells manufacture and release a protein,................., a member of the tumor growth factor β superfamily, that restricts the size of individual skeletal muscle cells.
What are the muscle striations?
- 1) A bands are anisotropic with polarized light; they usually stain dark. They contain both thin and thick filaments, which overlap and interdigitate. Six thin filaments surround each thick filament
- 2) I bands are isotropic with polarized light and appear lightly stained in routine histologic preparations. They contain only thin filaments.3) H bands are light regions transecting A bands; they consist of thick filaments only.
- 4) M lines are narrow, dark regions at the center of H bands formed by several cross-connections (M-bridges) at the centers of adjacent thick filaments.
- 5) Z disks (lines) are dense regions bisecting each I band.Z disks contain α-actinin and Cap Z, two proteins that bind to thin filaments and anchor them to Z disks with the assistance of nebulin.
- Desmin, aided by plectin, anchors Z disks to each other. Peripherally located Z disks are anchored to regions of the sarcolemma, known ascostameres, by vinculin and dystrophin.
Z disks contain ....................., two proteins that bind to thin filaments and anchor them to Z disks with the assistance of nebulin
α-actinin and Cap Z
Which protein anchors Z disks to each other?
Desmin, aided by plectin
Peripherally located Z disks are anchored to regions of the sarcolemma, known ascostameres, by ......................................
vinculin and dystrophin.
What is the function of dystrophin?
- actin-binding protein normally present in small amounts in the sarcolemma.
- Dystrophin also stabilizes the sarcolemma and acts as a link between the cytoskeleton and the extracellular matrix.
What are the five thin myofilaments?
What is the structure and function of F actin?
- A polymer of G-actin monomers arranged in a double helix.
- Each monomer possesses an active site that can interact with myosin.
- F-actin is present as filaments (with a diameter of 5–7 nm) that exhibit polarity, having a plus (+) and a minus (-) end, where the plus end is tethered to cap Z of the Z disk and the minus end, capped by tropomodulin, is located at the H band and is the growing end of the F-actin.
- F-actin loses and gains back G-actin molecules at both its plus and minus ends, but this turn over rate is very slow, occurring over a period of several days, whereas in other cells this turnover occurs every few minutes.
Tropomyosin molecules are about 40 nm in length. They bind ........................
head to tail, forming filaments that are located in the grooves of the F-actin helix.
What is the composition of troponin?
- Troponin is associated with each tropomyosin molecule and is composed of the following:
- Troponin T (TnT), which forms the tail of the molecule and functions in binding the troponin complex to tropomyosin.
- Troponin C (TnC), which possesses four binding sites for calcium. It may be related to calmodulin.
- Troponin I (TnI), which binds to actin, inhibiting interaction of myosin and actin.
What is the structure and function of nebulin?
- Nebulin is a long, inelastic protein. Two nebulin molecules wrap around each thin filament and assist in anchoring it to the Z disk.
- Each nebulin molecule is embedded in the Z disk by its carboxy terminal but does not span the entire Z disk.The amino terminal of each nebulin molecule ends in the A band, at or near the free end of its thin filament.
- Nebulin in skeletal muscle is thought to determine the length of its associated thin filament, although in cardiac muscle it extends only one-quarter of the length of the thin filament
...............caps the minus end of each thin filament and prevents the addition of more G-actin molecules to the growing end.
Thick filaments each contain approximately 250 ........... molecules arranged in an antiparallel fashion and three associated proteins—.......,.......,........
myosin II/myomesin, titin, and C protein
Myosin II is composed of .................................................
two identical heavy chains and two pairs of light chains
What is the structure of myosin?
- Myosin heavy chains consist of a long rodlike “tail” and a globular “head.” The tails of the heavy chains wind around each other in an α-helical configuration.Tails function in the self-assembly of myosin molecules into bipolar thick filaments. Actin-binding sites of the heads function in contraction.
- Myosin light chains are of two types; one molecule of each type is associated with the globular head of each heavy chain.
What is the result of digestion of myosin?
1) The enzyme trypsin cleaves myosin into light meromyosin (part of the tail portion) and heavy meromyosin (the two heads and the remainder of the tail)
2) The enzyme papain cleaves the heavy meromyosin, releasing the short tail (S2 fragment) and the two globular heads (S1 fragments). These S1 fragments have adenosine triphosphatase (ATPase) activity but require interaction with actin to release the noncovalently bound adenosine diphosphate (ADP) and Pi.
What is the function of Myomesin?
is a protein at the M line that cross-links adjacent thick filaments to one another to maintain their spatial relations
........... binds to thick filaments in the vicinity of M lines along much of their lengths (between the M line and the end of the thin filament in the vicinity of the A–I junction). This region of the A band is referred to as the ...............
C protein /C zone
What is the function of titin?
- Titin is a large linear springy protein that displays axial periodicity.
- It forms an elastic lattice that parallels the thick and thin filaments, and two titin filaments anchor each thick filament to the Z disk, thus maintaining their architectural relationships to each other.
- Each titin molecule extends from the Z disc to the M line
- The amino terminal of the titin molecule spans the entire thickness of the Z disk and binds to α-actinin and Z proteins.
- The carboxyl terminal of the titin molecule spans the entire M line and overlaps with titin molecules from the other half of the same sarcomere, and binds to the protein myomesin.
- Within the I band, in the vicinity of the Z disk, titin interacts with thin filaments.Within the A band, titin interacts with C protein.
The side-by-side relationship between the myosin and actin filaments is maintained by........
titin extends from ........... to..............
Z disk/ M line
Which part of sarcomere does not change in length during contraction?
True or false, during contraction thick and thin filament shorten
- During contraction, thick and thin filaments do not shorten but increase their overlap
What is the change observed in sarcomere during contraction?
- Thin filaments slide past thick filaments and penetrate more deeply into the A band, which remains constant in length.
- I bands and H bands shorten as Z disks are drawn closer together.
Describe the Ca dynamic during the contraction?
- Depolarization, accompanied by the release of Ca2+, triggers the binding of actin and myosin, leading to muscle contraction.
- The sarcolemma is depolarized at the myoneural junction.T tubules convey the wave of depolarization to the myofibrils.
- Voltage-sensitive dihydropyridine (DHP) receptors alter their conformation as a function of membrane depolarization.
- Ca2+ is released into the cytosol at the A–I junctions via Ca2+-release channels (junctional feet, ryanodine receptors) of the SR terminal cisternae that are opened by activated DHP receptors.
- As long as the Ca2+ level is sufficiently high, the contraction cycle will continue.
- In the resting state, the myosin-binding sites on thin (actin) filaments are partially covered by tropomyosin. Also, TnI is bound to actin and hinders myosin–actin interaction. Ca2+ binding by TnC results in a conformational change that breaks the TnI–actin bond; tropomyosin shifts its position slightly and uncovers the myosin-binding sites (active state)
- Relaxation occurs when Ca2+ concentration in the cytosol is reduced enough that TnC loses its bound Ca2+.
- As a result, tropomyosin returns to its resting position, covering actin's binding sites and restoring the resting state.
- Relaxation depends on a Ca2+ pump in the SR, which pumps Ca2+ from the cytosol to the inner surface of the SR membrane to be bound by calsequestrin.
DHP and Ryanodine receptors are on .... and...... respectively
Ca2+ is released into the cytosol at the........................
Relaxation occurs when ............................................
Ca2+ concentration in the cytosol is reduced enough that TnC loses its bound Ca2
What is rigor mortis?
- Rigor mortis is a postmortem rigidity appearing as hardening of skeletal muscles caused by the inability of muscle cells to synthesize ATP. As a result, myosin remains bound to actin, and the muscles remain contracted
- ATP is required to cause separation of the cross-bridges from the actin
- filaments during the relaxation process
What is the difference between a muscle fiber contraction and a muscle contraction?
- Fiber--> all or none
- Muscle--> variable strength of contraction
What are concentric and isometric contraction?
- Concentric--> sarcomere shorten
- Isometric--> sarcomere remain the same
How is the innervation of skeletal muscle?
Innervation consists of motor nerve endings (myoneural junctions) and two types of sensory nerve endings (muscle spindles and Golgi tendon organs). Both types of sensory nerve endings function in proprioception
What are the structural component of myoneural junction?
- The axon terminal lacks myelin but has a Schwann cell on its nonsynaptic surface.The membrane on the synaptic surface of the axon terminal is called the presynaptic membrane.The axon terminal contains mitochondria, synaptic vesicles (containing the neurotransmitter acetylcholine), and SER elements.
- The synaptic cleft is a narrow space between the presynaptic membrane of the axon terminal and the postsynaptic membrane (also known as the motor end plate) of the muscle cell. The synaptic cleft contains an amorphous external lamina, a basal laminalike material, derived from the muscle cell.
- Muscle cell near the myoneural junction: Sarcolemmal invaginations (of the postsynaptic membrane), called junctional folds, are lined by an external lamina and extend inward from the synaptic cleft. Acetylcholine receptors are located in the postsynaptic membrane.The sarcoplasm is rich in mitochondria, ribosomes, and rough endoplasmic reticulum (RER).
What is the sequence of neuromuscular transmission?
- The presynaptic membrane is depolarized and voltage-gated Ca2+ channels open, permitting the entry of extracellular Ca2+ into the axon terminal.
- The rise in cytosolic Ca2+ triggers the synaptic vesicles to release acetylcholine in multimolecular quantities (quanta) into the synaptic cleft. The released acetylcholine binds to receptors of the postsynaptic membrane, resulting in depolarization of the sarcolemma and generation of an action potential.
- The enzyme, acetylcholinesterase located in the external lamina lining the junctional folds of the motor end plate degrades acetylcholine, thus ending the depolarizing signal to the muscle cell.
- Acetylcholine is recycled as choline and is returned to the axon terminal to be recombined with acetyl coenzyme A (CoA) (from mitochondria) under the influence of the enzyme choline acetyl transferase to form acetylcholine, which is then stored in synaptic vesicles.
- Membranes of the emptied synaptic vesicles are recycled via clathrin-coated endocytic vesicles
What is the structure of muscle spindle?
- The muscle spindle (neuromuscular spindle) is an elongated, fusiform sensory organ within skeletal muscle that functions primarily as a stretch receptor.
- It is bounded by a connective tissue capsule enclosing the fluid-filled periaxial space and 8 to 10 modified skeletal muscle fibers (intrafusal fibers).
- Normal skeletal muscle fibers (extrafusal fibers) surround it.It is anchored via the capsule to the perimysium and endomysium of the extrafusal fibers
What is the function of muscle spindle?
1)Stretching of a muscle also stretches the muscle spindle and thus stimulates the afferent nerve endings to send impulses to the central nervous system
- 2)The response is to both the rate (phasic response) and duration (tonic response) of stretching.
- 3)Depolarization of γ-efferent neurons also stimulates the intrafusal nerve endings; the rate and duration of the stimulation are monitored in the same way as stretching.
4) Muscle overstimulation results from stretching at too great a frequency or for too long a time. Overstimulation causes stimulation of α-efferent neurons to the muscle, initiating contraction and thus counteracting the stretching
What is GTO?
- The Golgi tendon organ, located in tendons, counteracts the effects of muscle spindles.
- It is composed of encapsulated collagen fibers that are surrounded by terminal branches of type Ib sensory nerves.
- It is stimulated when the muscle contracts too strenuously, increasing tension on the tendon. Impulses from type Ib neurons inhibit α-efferent (motor) neurons to the muscle, preventing further contraction.
The main difference between muscle spindle and GTO is that............
the spindle detects muscle length and changes in muscle length, whereas the tendon organ detects muscle tension as reflected by the tension in itself
What are the features of cardiomyocyte?
- May branch at their ends to form connections with adjacent cells.
- Contain one centrally located nucleus, or occasionally two nuclei.
- Contain glycogen granules, especially at either pole of the nucleus, and the sarcoplasm is rich in myoglobin.
- Possess thick and thin filaments arranged in poorly defined myofibrils.
- Exhibit a cross-banding pattern identical to that in skeletal muscle.
- Do not regenerate; injuries to cardiac muscle are repaired by the formation of fibrous connective (scar) tissue by fibroblasts
Shape of skeletal/cardiac/SMC
Long, cylindrical/Blunt-ended, branched/ Short, spindle shaped
Nuclei of skeletal/cardiac/SMC
Many, peripheral/ One or two, central/ One, central
Striations of skeletal/cardiac/SMC
T-tubules and SR of skeletal/cardiac/SMC
Has triads at A–I junctions/Has dyads at Z disks/ Has caveolae (but no T tubules) and some smooth endoplasmic reticulum
Gap junctions of skeletal/cardiac/SMC
No/ Yes (in intercalated disks)/ Yes (in sarcolemma); known as the nexus
Sarcomere of skeletal/cardiac/SMC
Regeneration of skeletal/cardiac/SMC
Restricted/ None/ Extensive
Voluntary contraction in skeletal/cardiac/SMC
Distinctive characteristics skeletal/cardiac/SMC
Peripheral nuclei/ Intercalated disks/ Lack of striations
What is the difference between T-tubules in cardiac muscles and skeletal muscles?
T tubules are larger than those in skeletal muscle and are lined by external lamina. They invaginate from the sarcolemma at Z disks, not at A–I junctions as in skeletal muscle.
SR in cardiac myocyte....
- is poorly defined and contributes to the formation of dyads, each of which consists of one T tubule and one profile of SR.
- SR is also present in the vicinity of Z disks as small, basketlike saccules known as corbular sarcoplasmic reticulum, a region rich in Ca2+-release channels (junctional feet) and, therefore, analogous to the SR terminal cisternae.
Calcium ions in cardiac myocytes...
- During relaxation, Ca2+ leaks into the sarcoplasm at a slow rate, resulting in automatic rhythm.
- Ca2+ also enters cardiac muscle cells from the extracellular environment via voltage-gated Ca2+ channels of T tubules and sarcolemma.
- In response to calcium entering through the voltage-gated Ca2+ channels, Ca2+ is released from the SR and corbular sarcoplasmic reticulum (both via ryanodine receptors) to cause contraction of cardiac muscle.The force of cardiac muscle contraction is directly dependent on the availability of Ca2+ in the sarcoplasm. During basal cardiac contraction, only 50% of the available calcium-binding sites of TnC are occupied.
What is the feature of mitochondria in cardiac myocytes?
Mitochondria are more abundant than in skeletal muscle; they lie parallel to the I bands and often are adjacent to lipids
What are atrial granules?
Atrial granules are present in the atrial cardiac muscle cells and contain the precursor of atrial natriuretic peptide, which acts to decrease resorption of sodium and water in the kidneys, reducing body fluid volume and blood pressure.
What are intercalated disks?
1) Intercalated disks are complex steplike junctions forming end-to-end attachments between adjacent cardiac muscle cells.
- 2) The transverse portion of intercalated disks runs across muscle fibers at right angles and possesses three specializations: fasciae adherentes(analogous to zonula adherentes) to which actin filaments attach, desmosomes (macula adherentes), and gap junctions
- 3) The lateral portion of intercalated disks has desmosomes and numerous large gap junctions, which facilitate ionic coupling between cells and aid in coordinating contraction; thus, cardiac muscle behaves as a functional syncytium
- arrow--> IC disk.
What are the general features of SMC?
nonstriated, fusiform cells that range in length from 20 µm in small blood vessels to 500 µm in the uterus of pregnant women. They contain a single nucleus and actively divide and regenerate. They are surrounded by an external lamina and a reticular fiber network and may be arranged in layers, small bundles, or helices (in arteries)
What are the features of the nuclei of SMC?
- The centrally located nucleus may not be visible in each cell in cross-sections of smooth muscle because some nuclei lie outside the plane of section.
- The nucleus in longitudinal sections of contracted smooth muscle has a corkscrew shape and is deeply indented
What are the features of organelles in SMC?
- Mitochondria, RER, and the Golgi complex are concentrated near the nucleus and are involved in synthesis of type III collagen, elastin, glycosaminoglycans, external lamina, and growth factors.
- Sarcolemmal vesicles (caveolae), present along the periphery of smooth muscle cells, may function in the uptake and release of Ca2+.
- SER is sparse and may be associated with caveolae.
How is the organization of filaments in SMC?
- Contractile filaments (actin and myosin) are not organized into myofibrils. They are attached to peripheral and cytoplasmic densities and aligned obliquely to the longitudinal axis of smooth muscle cells.
- Thick filaments (composed of myosin II) are each surrounded by as many as 15 thin filaments.
- In contrast to striated muscle, the heads of the myosin molecules all point in the same direction.
- Thin filaments are composed of actin, caldesmon, tropomyosin, and calponin.
- Caldesmon functions similarly to TnT and TnI.
- Intermediate filaments are attached to cytoplasmic densities and include vimentin and desmin in vascular smooth muscle cells and desmin only in nonvascular smooth muscle cells.
.................... are believed to be analogous to Z disks, contain α-actinin, and function as filament attachment sites
..............between smooth muscle cells facilitate the spread of excitation and are collectively called a .................
what is the difference between contraction of SMC and skeletal muscles?
Contraction of smooth muscle occurs more slowly and lasts longer than contraction of skeletal muscle because the rate of ATP hydrolysis is slower.
What is the role of Ca is SMC?
- All comes from ECF
- The contraction cycle is stimulated by a transient increase in cytosolic Ca2+.
- Ca2+ binds to calmodulin, altering its conformation.The Ca2+–calmodulin complex activates the enzyme myosin light-chain kinase, which catalyzes phosphorylation of one of the light chains of myosin.
- In the presence of Ca2+, the inhibitory effect of the caldesmon–tropomyosin complex on the actin–myosin interaction is eliminated (caldesmon masks the active site of G-actin).
- Another inhibitor of contraction is calponin, which, when phosphorylated, loses its inhibitory capability.
- The globular head of phosphorylated myosin interacts with actin and stimulates myosin ATPase, resulting in contraction.
- As long as myosin is in its phosphorylated form, the contraction cycle continues.
- Dephosphorylation of myosin disturbs the myosin–actin interaction and leads to relaxation.
How is contraction triggered in each type of SMC?
- In vascular smooth muscle, contraction is usually triggered by a nerve impulse, with little spread of the impulse from cell to cell.
- In visceral smooth muscle, it is triggered by stretching of the muscle itself (myogenic); the signal spreads from cell to cell.
- In the uterus during labor, it is triggered by oxytocin.
- In smooth muscle elsewhere in the body, it is triggered by epinephrine.
What are the features of myoepithelial cells?
- In certain glands, these cells share basal laminae of secretory and duct cells.
- They arise from ectoderm and can contract to express secretory material from glandular epithelium into ducts and out of the gland.
- Although generally similar in morphology to smooth muscle cells, they have a basketlike shape and several radiating processes.
- They are attached to the underlying basal lamina via hemidesmosomes.
- They contain actin, myosin, and intermediate filaments, as well as cytoplasmic and peripheral densities to which these filaments attach.
- Contraction is similar to that of smooth muscle and occurs via a calmodulin-mediated process.
- In lactating mammary glands, they contract in response to oxytocin. In lacrimal glands, they contract in response to acetylcholine.
What are the features of myofibroblasts?
- Although they resemble fibroblasts, they possess higher amounts of actin and myosin and are capable of contraction.
- They may contract during wound healing to decrease the size of the defect (wound contraction).