micro anatomy muscle

7/28/2019 Micro Anatomy Muscle

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Microanatomy: Muscle

There are three types of muscle: skeletal, cardiac, and smooth muscle. Skeletal muscle is surrounded by the epimysium, a layer of dense connective tissue. The perimysium,

derived from the epimysium, surrounds bundles or fascicles of muscle cells, also called muscle fibers.

Each muscle fiber within a fascicle is surrounded by the endomysium, a thin layer of reticular fibers

and extracellular matrix closely associated to a basal lamina enveloping each muscle cell. Skeletal muscle cells are multinucleated cells, resulting from the fusion of myoblasts. Each skeletal

muscle cell is surrounded by a plasma membrane (called sarcolemma). The sarcolemma is

surrounded by a basal lamina and satellite cells. The sarcolemma projects long processes, called

transverse tubules or T tubules, deep into the cytoplasm (called sarcoplasm). The sarcoplasm

contains mitochondria (called sarcosomes). Each T tubule is flanked by sacs of the endoplasmic

reticulum (called sarcoplasmic reticulum) forming a tripartite structure called a triad, found at the

junction of the A band and I band. The nuclei are located at the periphery of the cell. An important

component of the sarcoplasm is the myofibril.

A myofibril is a linear repeat of sarcomeres. Each sarcomere consists of two major cytoskeletalmyofilaments: actin and myosin. Note the difference between myofibril and myofilament. The

arrangement of these two myofilaments generates a banding pattern (or striation), characteristic ofskeletal and cardiac muscle tissue. There is an A band (dark) and I band (light). The A band is at the

center of the sarcomere; the Z disk bisects the I band. The A band is bisected by the H band, which

contains creatine kinase. The M line runs through the midline of the H band.

A sarcomere is limited by two adjacent Z disks. Actin inserts into each side of the Z disk. Myosinmyofilaments do not attach to the Z disk. Actin is associated with the tropomyosin-troponin complex

(formed by troponins I, C, and T) and nebulin. Myosin (called myosin II) consists of two identical

heavy chains (with a globular head) and two pairs of light chains. The globular heads have an actin-

binding region, and ATP-binding region, and a light chain-binding region. Titin is associated with

myosin.


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Each Z disk is encircled by the intermediate filament desmin. Desmin filaments are linked to eachother by plectin. The desmin-plectin complex forms a lattice with the opposite ends attached to

costameres in the sarcolemma. This arrangement stabilizes the myofibrils in the sarcoplasm during

muscle contraction.

During muscle contraction, the length of myosin and actin myofilaments does not change. The lengthof the sarcomere decreases because actin and myosin slide past each other, represented by a

reduction in the width of the I band and H band. ATP is an energy source for muscle contraction.

Creatine phosphate (produced in sarcosomes) is a back up mechanism to maintain steady levels of

ATP during muscle contraction. Creatine kinase catalyzes a reversible reaction generating creatine

and ATP from the hydrolysis of creatine phosphate.

The neuromuscular junction is a specialized structure formed by a nerve associated with a targetmuscle. Inside the muscle, a motor nerve gives rise to numerous branches, each innervating a single

muscle cell. The motor nerve and its innervating branches form a motor unit.

An excitation-contraction signal is produced by the release of acetylcholine from a presynaptic buttoninto a primary synaptic cleft, an invagination on the surface of a muscle cell coated with basal lamina

containing acetylcholinesterase. The primary synaptic cleft forms secondary synaptic clefts, also

covered by basal lamina. Crests of the secondary synaptic clefts contain acetylcholine receptors.

An action potential depolarizes the sarcolemma, and the action potential travels inside the muscle cellalong T tubules, which are in contact with channels of the sarcoplasmic reticulum containing calcium.Calcium ions are released, bind to troponin C, and initiate contraction by regulating myosin-actin

interaction. When depolarization ends, calcium ions are pumped back into the sarcoplasmic reticulum

channels and bind to calsequestrin.

Botulinum toxin binds to the presynaptic membrane of the nerve terminal and blocks the release ofacetylcholine. Curare binds to the acetylcholine receptor, prevents binding of acetylcholine, and

induces muscle paralysis. In myasthenia gravis, an autoimmune disease that produces fatigue with

exercise, autoantibodies bind to the acetylcholine receptor and prevent binding of acetylcholine.

Muscular dystrophies are a group of congenital muscular diseases characterized by muscle weakness,atrophy, serum levels increases of muscle enzymes, and destructive changes in muscle tissue.

The following protein complexes, some of them part of the dystrophin-associated protein (DAP)complex, are present in the sarcoplasm or in the sarcolemma adjacent to the sarcolemma. Theyprovide mechanical stabilization during muscle contraction:

o 1. Dystroglycan complex consists of dystroglycan- and dystroglycan-. Dystroglycan- bindsto the chain of laminin-2, and dystroglycan- binds to dystrophin. No primary defects in the

dystroglycan complex have been identified.

o 2. Sarcoglycan complex consists of six transmembrane subunits (, , , , , and ).Sarcoglycanopathies (for example, limb-girdle muscular dystrophies) are caused by defects in

components of the sarcoglycan complex.

o 3. Dystrophin binds the dystroglycan complex to actin in the sarcoplasm. Duchenne's musculardystrophy, an X-linked recessive condition, is caused by a deficiency in dystrophin. The

absence of dystrophin results in the loss of syntrophins and other components of the DAP

complex.o 4. Dystrobrevin ( and subunits), present in the sarcoplasm.o 5. Syntrophins (, 1, 2, 1, and 2 subunits) are found in the sarcoplasm and bind to

dystrophin and dystrobrevin.

o 6. Sarcospan, a transmembrane protein. Satellite cells are closely associated to skeletal muscle cells and are covered by a basal lamina. In

mature muscle, satellite cells are quiescent. Activated satellite cells activated by trauma or mechanical

stress can self-renew and proliferate. The expression of myogenic regulatory factors (for example,

Myf5 and MyoD) activates satellite cells, which become myogenic precursor cells (to form muscle

cells) or side-population cells (to differentiate into hematopoietic cells).


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The neuromuscular spindle is a specialized encapsulated sensor of the contraction of various muscles.It contains sensory and motor components and specialized muscle fibers called intrafusal fibers

(designated nuclear bag fiber and nuclear chain fiber). Intrafusal fibers are in parallel with the

striated extrafusal fibers. When extrafusal fibers contract, the neuromuscular spindle becomes slack.

This information is transmitted to the spinal cord, which activates gamma motor neurons that stretch

the spindle. In contrast to the neuromuscular spindle, the Golgi tendon organs are located in series

with the extrafusal muscle fibers. They provide information about the force of contraction of the

skeletal muscle.

There are three major types of skeletal muscle fibers: red fibers (involved in maintenance of posture),white fibers (responsible for rapid contraction), and intermediate fibers (a combination of the

characteristics of red and white fibers). Muscles contain a mixture of the three types of fibers.

Cardiac muscle consists of branched cylindrical cells called cardiocytes. They contain a centralnucleus and myofibrils in the cytoplasm. The organization of the sarcomere is similar to skeletal

muscle. The following differences are observed:

o (1) T tubules and short portions of the sarcoplasmic reticulum form diads (instead of triads).o (2) Diads are found at the level of the Z disk (instead of the A-I band junction).o (3) Mitochondria contain abundant cristae.o (4) Cardiocytes are joined end-to-end by intercalated disks.o (5) Intercalated disks display steplike arrangement with yransverse portion (containing

desmosomes and fasciae adherentes), and longitudinal portion (where gap junctions located).

A specialized type of cardiac fiber is the Purkinje fiber, a glycogen-rich cell with fewer myofibrils,involved in conductivity.

Smooth muscle cells are found in the wall of the alimentary tube, urinary excretory passages,respiratory tract, uterus, and blood vessels.

Smooth muscle cells are spindle-shaped, tapering cells, with a central nucleus and surrounded by abasal lamina. We discussed the ability of smooth muscle cells to synthesize and secrete components of

collagen and elastic fibers. The cytoplasm contains actin, myosin, and intermediate filaments.

A typical feature of muscle cells are caveolae, regarded as a primitive T tubule system. Caveolaedevelop from lipid rafts, a domain in the plasma membrane enriched in cholesterol and sphingolipids.

The protein caveolin binds to cholesterol. Caveolae are not seen when the caveolin gene is notexpressed. The detachment of caveolae forms pynocytotic vesicles, involved in vesicular trafficking

and signaling.

The contraction of smooth muscle cells differs from skeletal and cardiac muscle cells. Smooth musclecells lack sarcomeres and troponin, and calcium ions initiate contraction from outside the cell, rather

than from the sarcoplasmic reticulum.

Myosin light-chain kinase is responsible for the calcium sensitivity of the contractile actin-myosincomponent of smooth muscle. An equivalent to the Z disk of striated muscle are the dense bodies.

In response to a stimulus, an increase in cytoplasmic calcium binds to calmodulin. The calcium-calmodulin complex activates myosin light-chain kinase, which catalyzes phosphorylation of the

myosin light chain and enables binding of activated myosin to actin.


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Spindle: small, consists of intrafusal fibers together with neural elements (Sensory and motor nerve

fibers) enclosed within double layer of connective tissue

2 kinds of intrafusal fibers designated by histological appearanceo Nuclear bag fiber (Static and dynamic): central sensory (noncontractile) bag like region)o Nuclear chain fiber: central portion contains chain like array of nuclei

Distal portion of both nuclear bag and nuclear chain fibers consist of striated muscle withcontractile properties

Sensory nerve fiberso Static (II) - connect with nuclear chain fibers and static nuclear bag fiberso Dynamic (Ia) - connect with all intrafusal fibers

Innervated by 2 types of afferent axons making contact with central region of intrafusal fiberso Large diameter alpha motor neuronso Small diameter gamma motor neurons innervate intrafusal fibers in spindle

Static gamma motor neurons - reach chain fibers and static nuclear bag fibers Dynamic motor neurons - innervate only dynamic bag fibers

When muscle is stretched, sensory nerve fibers are activatedo Ia fivers innervating dynamic nuclear bag fibers respond to rate of change of muscle stretcho Through reflex arc in SC, firing of muscle spindle sensory nerves activates contraction of

extrafusal fibers via alpha motor neurons

Gamma MN modulate tension on intrafusal fibers to adjust sensitivity of muscle spindleo Stimulation of dynamic gamma MN increases tension on the dynamic nuclear bag fibers

increasing sensitivity to rate of muscles stretch


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o Stimulation of static gamma MN increase overall responsiveness in nuclear chain fibers andstatic nuclear bag fivers but decreases the dynamic nuclear bag response

Intrafusal muscle fibers are in parallel with extrafusal muscle fiberso When extrafusal MF contract, muscle spindle becomes slacko If spindle remains slack, no further info about changes in muscle length can be transmitted

to spinal cord

o Situation is corrected by feedback control mechanism by which sensory region of spindleactivates gamma motor neurons which contract the poles of the spindle (contractile

region) spindle stretches

Golgi tendon organs - located in series with the extrafusal fiberso Provide info about tension or force of contraction of skeletal muscleso Monitor force of muscle contractiono Consists of free Ib sensory nerve endings in the collagen fivers of the tendon connecting

muscle to bone

As muscle contracts, tension of the tendon increase , thereby causing firing of the Ibnerve fibers

Provides negative feedback to alpha motor neuronso Golgi tendon reflex: protects the muscle from excessively heavy loads by causing muscle to

t relax and drop the load

Neuron from GTO fires Motor neuron is inhibited Muscles relaxes Load is dropped

I. Muscle receptors and proprioceptionA. Muscle spindle- collections of 6-8 specialized muscle fibers

1. Specialized receptors that signal length and the rate of change of length (velocity) ofthe muscle

2. Intrafusal fibersB.

Types of muscle spindle fibers1. Nuclear chain fibers: nuclei aligned in a single row in center of fiber. Signal

information about static length of the muscle

2. Nuclear bag fibers: nuclei collected in a bundle in middle of fibera. Static: signal info about the static length of the muscleb. Dynamic nuclear bag fiber: signal info about the rate of change of muscle

length


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c.C. Sensory innervation of muscle spindles - signals muscles length and velocity to CNS

through 2 types of specialized sensory fibers that innervate intrafusal muscles

1. Group 1a afferents: primary afferentsa. Wrap around all 3 types of intrafusal fibersb.

Provide info about length and velocityc. Respond at highest rate when muscle is actively stretching but also signalsthe static length of he muscle

2. Group II afferents:a. Innervate ends of nuclear chain fibers and static nuclear bag fibersb. Signal info about muscle length onlyc. Increases firing rate linearly as function of muscle length

D. Gamma motor neurons1. Innervate intrafusal fibers to keep the muscle spindle taut and sensitive to stretch2. Alpha-gamma co activation

a. Muscle starts at certain length, encoded by firing of Ia afferentb.

When muscles is stretched, muscle spindle becomes stretched sending moreIa afferent signals

c. When muscles is released from stretch and contracts, the muscle spindlebecomes slack causing Ia afferents to cease firing

d. Muscle spindle is rendered insensitive to further stretches of musclee. To restore sensitivity, gamma motor neurons fire and cause the spindle to

contract, thereby becoming taut an able to single the muscle length again

E. Golgi tendon organ - specialized receptor located between the muscle and tendon1. GTO is located in series with muscle spindle, and signals info about the load or force

being applied to muscle


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2. Innervated by primary afferents called Group Ib fibers which have specializedendings that weave in between collagen fibers

3. When force applied to a muscle, GTO is stretched causing collagen fibers to squeezeand distort membrane of primary afferent sensory endings

a. Afferent is depolarized and fire action potential to signal amount of force

micro anatomy muscle

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