Structure of Muscle Tissue

Describe the structure and formation of myofibrils

Individual sarcomeres are joined end to end at Z-discs extending more or less from one end of the cell to the other. Each of these long cylindrical strands of sarcomeres is termed a myofibril.

What does IGF-1 do?

Insulin Like Growth Factor 1 (IGF-1) stimulates protein synthesis and growth in muscle (i.e. it is antagonistic to the effects of myostatin)

What is myasthenia gravis?

Myasthenia gravis is an autoimmune disease with progressive muscular weakness and atrophy. It is characterized by a reduction in the number of acetylcholine receptors in the sarcolemma at the NMJ. Circulating auto-antibodies bind to the receptors, which are then removed by endocytosis and lysosomal digestion. Lack of trophic input to the muscle causes denervation atrophy.

What does myostatin do? What is it? How is it activated?

Myostatin exerts an inhibitory effect on muscle growth and differentiation (regulating normal development as well as playing a role in certain pathological conditions). It is a cytokine that circulates in an inactive form; proteolytic cleavage is necessary for activation. It down regulates MyoD transcription.

The spindle apparatus is the basis for the ...

afferent limb of the stretch reflex and it also allows us to know our position in space (proprioception)

Myofibrils are composed of x: these are the individual polymers of myosin (thick filaments) and actin and its associated proteins (thin filaments)

bundles of myofilaments

The regulation of x is central to the mechanism of muscle contraction.

cytoplasmic calcium concentration

What is the H-band?

Distance between end of actin molecules from opposite ends of the sarcomere (no overlap of actin and myosin here)

Describe the motion of the sarcomere

During contraction the I and H bands shorten and the Z lines move together this shortening the entire sarcomere; the opposite occurs with stretch or lengthening. The length of the A band never changes.

Describe the structure and development of muscle cells

Each muscle cell (also called muscle fiber or myofiber) is a multi-nucleated cell with numerous peripherally located nuclei just beneath the plasma membrane (called sarcolemma in muscle). Cross-striations (seen in b in the image) are the result of the regular cytoarchitectural arrangement of the myofilaments. The cytoplasm of the cells (sarcoplasm) is dominated by the contractile filaments, but is also rich in mitochondria, a well developed smooth endoplasmic reticulum (called the sarcoplasmic reticulum) surrounding the myofilaments (actin and myosin)

Myostatin inhibitors have the potential to x; studies are ongoing in this area. Over the counter supplements or "mysotatin inhibitors" have not been adequately researched.

increase muscle mass

Smooth muscle is not x

striated

Skeletal and Cardiac muscle are both types of x muscle

striated muscle (exhibit cross striations at the light microscopic level)

What are the three major proteins of thin filaments?

1) Actin - a globular protein that polymerizes in a double helical structure forming the thin filament 2) Tropomyosin - a protein that also forms a double helical structure lying in the groove of the actin helix. It acts with the troponin complex to regulate myosin-actin binding. 3) Troponin Complex consisting of 3 globular subunits: - TnI - an actin binding protein that prevents binding of actin to myosin - TnT - a tropomyosin binding protein that holds the troponin complex to actin - TnC - a calcium binding protein, the essential step in initiation of muscle contraction

What are the factors affecting hypertrophy?

1) Age: reduced ability to hypertrophy with advanced age 2) Nutrition: adequate supply of amino acids necessary 3) Hormones: testosterone (and to a lesser extent estrogen), growth hormone, FGF and IGF promote hypertrophy; cortisol causes muscle breakdown and atrophy Taking anabolic steroids (including testosterone) as PEDs increases hypertrophy (but is illegal without a medical prescription!)

What are the three connective tissue layers in each muscle?

1) Epimysium - dense irregular connective tissue that surrounds all of the fascicles that constitute a muscle (i.e. entire muscle) 2) Perimysium - a thinner layer of dense irregular connective tissue that surrounds individual fascicles 3) Endomysium - a fine layer of reticular fibers that surround individual muscle fibers

What are the three major proteins of the thick filaments?

1) Myosin Heavy Chain - a large protein with two portions, an alpha helical "rod" portion and a globular "head" portion that has an ATP and actin binding site 2) Myosin Light Chain 1 and Myosin Light Chain 2 - light chain phosphorylation helps regulate calcium stimulation of contraction. This is more important in smooth muscle

What are the three types of muscle fibers?

1) S (Slow-twitch or Type I) [1 in diagram below] have small motor neurons (MN), produce small amounts of force for prolonged time periods (hence also called fatigue resistant FR). Have abundant thin, red fibers (high in myoglobulin), numerous mitochondria and contract weakly but for long periods of time; high concentration in back muscles for long, slow contraction necessary for sustained posture. 2) FR (Fast-twitch, fatigue resistant or Type IIa) [2 in below diagrams] have medium sized MNs, produce moderate amounts of force for moderate durations. Medium sized, paler fibers with moderate amounts of myoglobulin; higher content in middle-distance swimmers, for example. 3) FF (Fast-twitch, fatiguable or Type IIb) [3 in below diagram] have large MNs, produce large amounts of force for short time periods. Large, white (low myoglobulin content) fibers with few mitochondria; adapted for rapid contraction and fine, precise movements; thus high concentration in extraocular and distal and finger muscles. Also found in short distance sprinters.

There are three histologically distinct types of muscle:

1) Skeletal (attach to bone and responsible for movement of body parts) 2) Cardiac 3) Smooth

What is a triad?

A triple structure seen in cross section consisting of two terminal cisternae flanking a T-tubule at the A-I band junction

What is a motor unit? What are the types of motor units?

An alpha motor neuron and all the muscle fibers it innervates; a neuron makes contact with muscle fibers of the same histochemical type. Muscles with many small motor units (ex. 1 neuron innervates 10 muscle fibers) associated with fine motor control (e.g. finger/hand muscles; extraocular muscles) Muscles with many large motor units (1 neuron innervates up to 2000 muscle fibers) associated with gross postural control (e.g. abdominal and back muscles) Most muscles have all 3 types of motor units which are recruited in the order of the size of their motor neurons

Describe muscular dystrophy

Congenital muscle diseases (various types including Duchenne's) with severe weakness, atrophy and destruction of muscle fibers; are caused by genetic mutations in the muscle transmembrane proteins of the dystrophin-glycoprotein complex. The progressive degeneration of skeletal muscle fibers places a constant demand on the satellite cells to replace the degenerating fibers. The satellite pool is ultimately exhausted. Research suggests that during this process additional myogenic cells are recruited from the bone marrow to supplement available satellite cells. These cells might be a target for future treatments for muscular dystrophies.

Describe the structure of an intercalated disc

Contain fascia adherens, macula adherens (desmosomes) and gap junctions. Above is an EM of cardiac muscle fiber showing fascia adherens (FA), macular adherens (MA), and gap junctions (GJ). The many gap junctions present are responsible for the electrotonic coupling between adjacent cardiac myocytes so the heart muscle contracts as a syncytium. Note the numerous mitochondria.

What can lead to disuse atrophy? What is involved in protein loss during atrophy?

Lack of use of exercise, prolonged bedrest and cast immobilization leads to decreased muscle protein synthesis and disuse atrophy (this occurs within 24 hours with casting!). Myostatin signaling as well as other pathways are involved in protein loss during atrophy. Atrophy also occurs with multiple disease states.

What is the M-line?

Located at the center of the sarcomere. The major proteins, C-protein and myomesin stabilize the thick filaments in register at the M line.

Denervation Atrophy

Loss of stimulation to the muscle cell at the neuromuscular junction leads to muscle atrophy

Describe structure, location and function of satellite cells

Responsible for muscle cell's limited ability to regenerate; are interposed just outside sarcolemma but inside the external lamina (difficult to identify in light microscopy). After injury some become activated, reenter the cell cycle, express myogenic regulator factors, and proliferate. As long as the external lamina remains intact, the myoblasts fuse to form myotubes which then mature into a new muscle fiber. Regenerated skeletal muscle has central nuclei. If the external lamina is disrupted, fibroblasts repair the injured site with resultant scar tissue formation.

What are the similarities between cardiac muscle and skeletal muscle? What are the differences?

Similarities: the contractile proteins, cross-striated appearance, and ultrastructure of the sarcomere unit are similar to skeletal muscle. Differences: 1) One (or two) centrally located nucleus per cell 2) Branching pattern of muscle fibers 3) The presence of intercalated discs which are highly specialized attachments that join cardiac muscle fibers together. The structural arrangement of the intercalated discs allows the heart to contract in a wringing fashion. 4) The T-tubules are more prominent in association with reduced SR cisternae, so diads are formed at the vicinity of the Z-line 5) There are more mitochondria, lipid droplets, glycogen and myoglobin in the sarcoplasm of cardiac muscle cells 6) The contraction of cardiac muscle is vigorous, rhythmic, and under the control of both the autonomic nervous system and circulating hormones.

Describe the structure and location of smooth muscle cells

Smooth muscle cells are fusiform, lack cross-striations and T-tubules, and have a single centrally located nucleus. They are found in the wall of tubular organs (in two planes); the iris and ciliary body of the eye, the scrotum, blood vessels and hair follicles. The cells are arranged as sheets joined by gap junctions (GJ) to allow intercellular communication regulating contraction of the entire sheet or bundle of smooth muscle. The arrows in the EM image depict the dense bodies containing a-actin which serve to anchor the actin filaments to the sarcolemma in order to transmit contractile force. The interaction of actin and myosin filaments during contraction is somewhat similar to that for skeletal muscle. Like cardiac muscle, control is both autonomic (adrenergic and cholinergic) and hormonal, but the NMJs are simple, no T-system is present, and the innervation tends to modify rather than initiate activity.

What is the Z-line or disc?

The Z-line serves as an anchor for thin filaments and the protein alpha-actinin is responsible for this function. The protein titin anchors the thick filaments to the Z-line; it also funtions in maintaining appropriate spacing of these filaments in the sarcomere. Titin extends from the end of the thick filament to the Z-line; it functions as a molecular spring which provides for passive elasticity of muscle and keeps thick filaments centered in the sarcomere. The protein nebulin wraps around the thin (actin) filaments and assists alpha-actinin in anchoring actin to the Z-line.

What is the A (anisotropic) Band?

The darker stained band seen in histological slides and is equivalent to the length of the myosin filament. It contains both the thick filament and the portion of the thin filament that overlaps with the thick filament. The extent of overlap depends on the degree of muscle contraction.

What is the I (isotropic) Band?

The lighter stained band seen in histological slides and is equivalent to the portion of thin filaments in adjacent sarcomeres that are not overlapping with thick filaments.

Describe the development of muscle cells

They are unusual cells in that they develop from the end to end fusion of precursor cells called myoblasts, resulting in extremely long multinucleated fibers.

Describe the structure and function of a transverse tubule

Transverse tubule (or T-tubule) is a tubular invagination of the muscle cell plasma membrane. These invaginations of the plasma membrane are normally aligned with the myofibrils at the A-I band junction. They are closely associated with the terminal cisternae of the sarcoplasmic reticulum, which is a highly specialized smooth endoplasmic reticulum. These two structures allow for contraction of myofibrils throughout the muscle cell quickly, despite the very large diameter of the cells. The T-tubule allows for changes in the membrane electrical potential to extend into the center of the cell and by virtue of the close linkage of the T-tubule, with the terminal cisternae of the sarcoplasmic reticulum, whose function is to serve as a reservoir for calcium ions.

Skeletal muscle is stimulated to contract by the release of the neurotransmitter x. Y receptors are located at the junctional folds of the sarcolemma.

x = acetylcholine (Ach) y = cholinergic Ach

Each anatomically identifiable skeletal muscle has a three dimensional structure maintained by x tissue layers. These connective tissue layers also serve as a route for both the y and z supply to access the muscle tissue.

x = connective y = nerve z = circulatory

The muscle spindle has an outer x, within which an y contains two types of modified muscle cells (intrafusal fibers). Z sensory fibers wrapped around the center of these are stimulated by change in length of intrafusal fibers in the spindle. W motor fibers modulate the sensitivity of the spindle by adjusting the tension in the intrafusal fibers, thus maintaining sensitivity to stretch during contraction.

x = connective tissue capsule y = inner capsule z = afferent w = efferent

There are different types of muscle fibers based on differences in x, y and z. Most muscles have w but u depends on function of a particular muscle.

x = contractile speed y = metabolic profile z = fiber morphology w = all 3 fiber types u = proportion

Muscle tissue is specialized of x and y in order to perform movements.

x = contractility y = excitability

Muscle cells are x and have a membrane and organelles which are specialized for y.

x = elongate y = contraction

Skeletal muscle is adaptive to use throughout life and occurs by changes in x and y.

x = fiber size y = fiber type

Physical exercise causes x (increase in cell size) of skeletal muscle fibers, where the increase in cell volume is due to an increase in size of y and the formation of new y. Smooth muscle fibers (e.g. uterus) are capable of x AND z (increase in cell number). Smooth muscle has modest w, but cardiac muscle for the most part cannot regenerate; therefore myocardial infarcts are replaced by connective tissue scars.

x = hypertrophy y = myofibrils z = hyperplasia w = regenerative potential

Cardiac muscle fibers are joined together by x shown by arrows. These x contain 3 types of junctional complexes: (name them)

x = intercalated discs 1) Fasciae Adherens 2) Maculae adherens (desmosomes) 3) Gap junctions

Cardiac and smooth muscle are both x muscle. Skeletal muscle is y.

x = involuntary (under control of hormones and autonomic nervous system) y = voluntary (under cerebral cortical control)

During development myoblasts differentiate from x. This differentiation is associated with expression of the transcription factors y, z and others and causes w.

x = mesodermal progenitor cells y = MyoD z = myogenin w = up-regulation of myofilament protein gene transcription

Skeletal muscles have sensory receptors (proprioceptors) called x which detect the amount of y of a muscle (i.e. length and rate of length changes).

x = muscle spindles y = stretch

Early myoblasts fuse to form multinucleated x that then mature into y. The x originally have centrally located nuclei which then become displaced to the periphery by newly synthesized z.

x = myotubes y = skeletal muscle fibers z = myofilaments Developing muscle fibers in cross (left) and longitudinal (right) section

In muscle, the synaptic junction between a motor axon and the muscle fiber is called a x which includes specializations of the muscle cell. The plasma membrane of the muscle cell has extensive y where the axon terminates on the muscle cell.

x = neuromuscular junction (NMJ) or motor end-plate y = junctional folds (JF)

The number of muscle fibers is determined x and remains essentially constant throughout life. Circumferential muscle growth occurs via y. y occurs by increasing the size of z AND the number of z per muscle cell. New muscle cells are not formed - instead z are formed and then enlarged.

x = prenatally y = hypertrophy z = myofibrils

Myofilaments are linked into a highly structured organization called the x, a unique structural feature of striated (skeletal and cardiac) muscle. x lines up end to end along the length of muscle fiber in small parallel bundles called y. This highly organized arrangement of thin and thick filaments is a specific banding pattern forms the basis for muscle contraction.

x = sarcomere y = myofibrils

Longitudinal growth occurs via adding new x at the ends of y; muscle cells therefore increase in length with skeletal growth.

x = sarcomeres y = myofibrils

All muscle fibers in a single motor unit are of the same fiber type. Motor neurons are recruited in order of size - called the x. Describe x.

x = the size principle As the synaptic drive on the motor neurons increase small motor neurons (S) are recruited first, followed by medium sized ones (FR) and finally large ones (FF). Allows automatic, smooth increase in force generation.

The motor axons lose x at the NMJ. The motor neuron and NMJ and the neural activity occurring there is responsible for y.

x = their myelin sheath y = a trophic effect on the target muscle cell