MUSCLE

TISSUE

Tayseer J. M. Afifi

Medical Student - IUG

OUTLINES

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INTRODUCTION

• Muscle tissue is the only one which has the property of contractility.
• Essentially all muscle cells are of mesodermal origin and differentiate by a gradual process to cell lengthening with abundant synthesis of the myofibrillar proteins actin and myosin.
• Three types of muscle tissue can be distinguished on the basis of morphologic and functional characteristics with the structure of each adapted to its physiologic role. These three types are:

1- Skeletal muscle.

2- Cardiac muscle.

3- Smooth muscle.

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FIGURE 10-1

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INTRODUCTION

• Muscle specialists refer to certain muscle cell organelles with special names.

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Cytoplasm

Smooth ER

Cell membrane & external lamina

Sarcoplasm

Sarcoplasmic Reticulum

Sarcolemma

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SKELETAL

MUSCLE

Skeletal Muscle

• Organization of Skeletal Muscle.
• Organization within muscle fibers.
• SR & transverse tubule system.
• Mechanism of contraction.
• Innervation.
• Muscle spindles & tendon organs.
• Skeletal muscle fibers type.

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Skeletal Muscle

• Skeletal muscle fibers, which are long, cylindrical multinucleated cells with diameters of 10-100 μm.
• Elongated nuclei are found peripherally just under the sarcolemma, a characteristic nuclear location unique to skeletal muscle fibers.
• Skeletal muscles are voluntary muscles except in:

* The upper third of esophagus.

* Some muscles of the pharynx.

* Cremasteric muscles of the spermatic cord.

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FIGURE 10-7

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FIGURE 10-8

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Skeletal Muscle

A small population of reserve progenitor cells called muscle satellite cells remains adjacent to most fibers of differentiated skeletal muscle.

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Organization of Skeletal Muscle

• Thin layers of C.T surround the fibers in all three types of muscle. They are best seen in skeletal muscle. They are arranged as follows:

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Organization of Skeletal Muscle

FIGURE 10-4

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FIGURE 10-4

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FIGURE 10-5

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Organization of Skeletal Muscle

• All three layers, plus the deep fascia which overlies the epimysium, are continuous with the tough C.T of a tendon at myotendinous junctions which join the muscle to bone, skin, or another muscle.

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Organization within Muscle fibers

• Myofibrils: Long cylindrical filament bundles run parallel to the long axis of the fiber.
• A Band: The dark bands on the myofibrils ( anisotropic ).
• I Band: The light bands on the myofibrils ( isotropic ).
• Z Disk: A dark transverse line bisect I band.
• Sarcomere: It is the functional subunit of contractile apparatus, extends from Z line to Z line. It is 2.5 μm in resting muscle.
• Mitochondria and SR are found between myofibrils.
• Myofibrils consist of an end-to-end repetitive arrangement of sarcomeres. Muscle transverse striations result from lateral registration of sarcomeres in adjacent myofibrils.

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Organization within Muscle fibers

• Myosin Filaments.
• They are 1.6-μm long and 15-nm wide, occupy A band at middle of sarcomere.
• They extend in the dark bands only.
• They consist of 2 identical heavy (thin, rodlike, motor) chains, twisted together as myosin tails. And 4 light chains contained on globular projections to form a head at one end of each heavy chain.
• Heads bind to actin filaments and ATP.

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Organization within Muscle fibers

• Actin Filaments.
• They are helical with 1-μm long and 8-nm wide, run between myosin filaments.
• Each G-actin monomer contains a binding site for myosin.
• They extend from the Z line till the middle of the dark band.
• The thin filaments have 2 tightly associated regulatory proteins:

1- Tropomyosin: located in the groove between the two twisted actin strands.

2- Troponin: has 3 subunits (TnT, attaches to tropomyosin. TnC, binds calcium. TnI, regulates actin-myosin interaction). Troponin attaches at specific site spaced along each tropomyosin molecule.

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Organization within Muscle fibers

• Cross-bridges between thin and thick filaments.

These bridges, which are known to be formed by the head of the myosin molecule plus a short part of its rodlike portion, are involved in the conversion of chemical energy into mechanical energy.

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Organization within Muscle fibers

• I bands are more lightly than A bands.
• The table below shows the important components of myofibril.

• H Zone: Light zone in the middle of A band, contains only myosin molecule.
• M Line: Bisects H zone, contains myosin binding protein myomesin and Creatine Kinase enzyme.

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SR & Transverse Tubule System

• SR contains pumps and proteins for Ca sequestration and surrounds the myofibrils.
• Ca release through voltage-gated channels is triggered by membrane depolarization produced by a motor nerve.
• In order to produce uniform contraction, the sarcolemma has transverse T-tubules.
• Transverse T-tubules are long finger like invaginations of cell membrane penetrate deeply into the sarcoplasm and encircle each myofibril near the aligned A- and I-band boundaries of sarcomeres.

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SR & Transverse Tubule System

• Adjacent to T-tubules are expanded terminal cisternae of SR, this complex of T-tubule and two terminal cisternae is called a triad.
• Triad complex functions:

1- Allows depolarization of sarcolemma in T-tubules to affect SR.

2- Trigger release of Ca ions into cytoplasm to initiate contraction of sarcomeres.

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Mechanism of Contraction

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Mechanism of Contraction

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Mechanism of Contraction

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Mechanism of Contraction

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Innervation

• Myelinated motor nerves branch out within the perimysial connective tissue, where each nerve gives rise to several terminal twigs.
• At the site of innervation, the nerve loses its myelin sheath and forms a dilated termination that sits within a trough on the muscle cell surface. This structure is called the motor end plate ,or neuromuscular junction.
• Synapses at axon terminal contains: 1- Mitochondria. 2- Synaptic vesicles: contains neurotransmitter Acetylcholine.
• Between axon and muscle is synaptic cleft. Adjacent to it, numerous junctional folds, which provide greater postsynaptic surface area and acetylcholine receptors.

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Muscle Spindles & Tendon Organ

• Striated muscles and myotendinous junctions provide the CNS with data through proprioceptors.
• Muscle spindles are stretch-detectors fascicles, also encapsulated by modified perimesyium. They contain concentric layers of flattened cells. These cells contain interstitial fluid and a few thin muscle fibers filled with nuclei and called intrafusal fibers.
• Sensory nerve axons penetrate muscle spindle and wrap around intrafusal fibers.
• Different types of sensory and intrafusal fibers mediate reflexes of varying complexity to help maintain posture and to regulate the activity of opposing muscle groups involved in motor activities such as walking.

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Muscle Spindles & Tendon Organ

• In tendons, near the insertion sites of muscle fibers, a connective tissue sheath encapsulates several large bundles of collagen fibers that are continuous with the collagen fibers that make up the myotendinous junction.
• These structures, known as Golgi tendon organs, contribute to proprioception by detecting tensional differences in tendons.

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Skeletal Muscle Fiber Types

CARDIAC

MUSCLE

Characteristics of Cardiac Muscle Fibers

• Cardiac muscle cells form complex junctions between interdigitating processes.
• Cells within one fiber often branch and join with cells in adjacent fibers.
• The heart consists of tightly knit bundles of cells, interwoven in spiraling layers that provide for a characteristic wave of contraction that resembles wringing out of the heart ventricles.
• Cardiac muscle cells have a striated banding pattern comparable to that of skeletal muscle.
• Each cardiac muscle cell usually has only one nucleus and is centrally located.
• Muscle cells is surrounded by a delicate sheath of endomysium with a rich capillary network.

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Characteristics of Cardiac Muscle Fibers

• A thicker perimysium separates bundles and layers of muscle fibers and in specific areas forms larger masses of fibrous connective tissue comprising the “cardiac skeleton.”
• Cardiac muscle is the presence of transverse lines that cross the fibers at irregular intervals where the myocardial cells join.
• These intercalated discs represent the interfaces between adjacent cells and consist of many junctional complexes.
• Transverse regions of these irregular, steplike discs are composed of many desmosomes and fascia adherens junctions.
• The less abundant, longitudinally oriented regions of each intercalated disc run parallel to the myofibrils and are filled with gap junctions.

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Characteristics of Cardiac Muscle Fibers

• These regions serve as “electrical synapses,” promoting rapid impulse conduction through many cardiac muscle cells.
• Mitochondria occupy up to 40% o the cell volume.
• Fatty acids, the major fuel of the heart, are stored as triglycerides in small lipid droplets. Glycogen granules may also be present.
• T-tubules in ventricular muscle fibers are well-developed. In atrial muscle T-tubules are much smaller or entirely absent. Sarcoplasmic reticulum is less well-organized. The junctions between its terminal cisterns and T-tubules form profiles called dyads rather than triads.

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Characteristics of Cardiac Muscle Fibers

• Cardiac muscle fiber contraction is intrinsic and spontaneous.
• Contractions are initiated, regulated, and coordinated locally by nodes of unique myocardial fibers specialized for impulse generation and conduction.
• Secretory granules are found near atrial muscle nuclei and are associated with small Golgi complexes. These granules release the peptide hormone atrial natriuretic actor (ANF) that acts on target cells in the kidney to affect Na excretion and water balance.

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SMOOTH

MUSCLE

Characteristics of Smooth Muscle

• Also called visceral muscle.
• Smooth muscle cells are fusiform.
• They are elongated, tapering, and unstriated cells, enclosed by an external lamina and a network of type I and type III collagen fibers comprising the endomysium.
• The cells stain uniformly along their lengths.
• Cross sections of smooth muscle show a range of cell diameters, with only the largest pro les containing a nucleus.
• All cells are linked by numerous gap junctions.

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The borders of the cell become scalloped when smooth muscle contracts and the nucleus becomes distorted.

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Characteristics of Smooth Muscle

• Concentrated near the nucleus are mitochondria, polyribosomes, RER, and vesicles of a Golgi apparatus. The short plasmalemma invaginations resembling caveolae (contain major Ca ion channels) are often numerous at the surface of smooth muscle cells.
• The fibers have rudimentary sarcoplasmic reticulum, but lack –tubules.
• Smooth muscle is not under voluntary motor control and its fibers typically lack well-defined neuromuscular junctions.
• The gastrointestinal tract smooth muscle is controlled by various paracrine secretions and in the uterus by oxytocin from the pituitary gland.
• Smooth muscle cells also supplement fibroblast activity, synthesizing collagen, elastin, and proteoglycans, with a major influence on the (ECM).

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Contraction in Smooth Muscle Cells

• The contractile activity of smooth muscle is generated by actin and myosin filaments arranged differently from striated muscle.
• The myofilaments crisscross the sarcoplasm obliquely.
• There is less cross bridges than in striated muscle.
• Thin filament is associated with calmodulin and Ca sensitive myosin light chain kinase (MLCK). NOT with troponin and tropomyosin.

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Contraction in Smooth Muscle Cells

• Actin inserts into anchoring dense bodes which contain α-actinin.
• Smooth muscle cells have an elaborate arrays composed of desmin, intermediate filament, also attached to dense bodies.
• Dense bodies include cadherins of desmosomes linking adjacent smooth muscle cells.
• Dense bodies transmit the contractile force.
• The endomysium and other connective tissue layers help combine the force generated into a concerted action, for example peristalsis in the intestine.

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Sites of Smooth Muscles

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Regeneration of

Muscle Tissue

Regeneration of Muscle Tissue

• Cardiac muscle has almost no regenerative capacity beyond early childhood. Defects or damage in heart muscle are generally replaced by scars.
• Skeletal muscle the tissue can undergo limited regeneration. The source of regenerating cells is believed to be the satellite cells.
• Smooth muscle is capable of an active regenerative response.

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Medical

Applications

Hypertrophy vs Hyperplasia

• Hypertrophy: a process characterized by increased cell volume.
• Hyperplasia: Tissue growth by an increase in the number of cells.
• Hyperplasia takes place very readily in smooth muscle, whose cells have not lost the capacity to divide by mitosis.
• The variation in diameter of muscle fibers depends on factors such as the specific muscle, age, gender, nutritional status, and physical training of the individual.
• Hyperplasia is rather frequent in organs such as the uterus, where both hyperplasia and hypertrophy occur during pregnancy.

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Myasthenia Gravis

• An autoimmune disorder characterized by progressive muscular weakness caused by a reduction in the number of functionally active acetylcholine receptors in the sarcolemma of the myoneural junction.
• This reduction is caused by circulating antibodies that bind to the acetylcholine receptors in the junctional folds and inhibit normal nerve muscle communication.

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Muscle Dystrophy

• Dystrophin is a large actin-binding protein located just inside the sarcolemma of skeletal muscle fibers which is involved in the functional organization of myofibrils.
• Mutations of the dystrophin gene can lead to defective linkages between the cytoskeleton and the ECM.
• Muscle contractions can disrupt these weak linkages, causing the atrophy of muscle fibers typical o this disease.

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Cardiac Ischemia

• The most common cardiac muscle injury or tissue damage is due to O2 .
• Mammalian cardiac muscle has little potential to regenerate because it lacks satellite cells.
• Some other creatures, fish and newborn mice, do form new cardiac muscle when it is partially removed.

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Muscle Tumors

• Leiomyomas are benign tumors commonly develop from smooth muscle fibers but are seldom problematic.
• Fibroids occur in the wall of the uterus, where they can become sufficiently large to produce painful pressure and unexpected bleeding.

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Review

Questions

The basal lamina of a muscle fiber is part o which structure?

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A. Perimysium

B. Epimysium

C. Fascia

D. Endomysium

E. Sarcoplasmic reticulum

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With the transmission electron microscope skeletal muscle fibers can be seen to contain structures called triads. What do the two lateral components of a triad represent?

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A. Attachment sites for thick myofilaments

B. Sites for calcium sequestration and release

C. Sites for impulse conduction into the fiber

D. Sites for ATP production

E. Sites for synthesis o proteins to be secreted outside the cell

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Which characteristic is unique to cardiac muscle?

A. Contain centrally located nuclei

B. Striated

C. Often branched

D. Multinucleated

E. Lack T-tubules

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In smooth muscle calcium released by the smooth ER initiates contraction by binding to what protein?

A. Actin

B. Calmodulin

C. Desmin

D. Myosin light chain kinase

E. Tropomyosin

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Which feature typifies T-tubules?

A. Evaginations of the sarcoplasmic reticulum

B. Sequester calcium during muscle relaxation, releasing it during contraction

C. Carry depolarization to the muscle fiber interior

D. Overlie the A-I junction in cardiac muscle cells

E. Rich supply o acetylcholine receptors

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Which characteristic is unique to smooth muscle?

A. T-tubules lie across Z lines

B. Each thick lament is surrounded by six thin filaments

C. Thin filaments attach to dense bodies

D. Cells are multinucleated

E. Cells have centrally located nuclei

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In one type of muscle, numerous gap junctions, desmosomes, and adherens junctions are specifically localized in which structures?

A. Myofilaments

B. Dense bodies

C. Sarcomeres

D. Neuromuscular spindles

E. Intercalated discs

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A 66-year-old man who lives alone has a severe myocardial infarction and dies during the night. The medical examiner’s office is called the following morning and describes the man’s body as being in rigor mortis. This state of rigor mortis is due to which one of the following?

A. Inhibition of Ca2+ leakage from the extracellular fluid and sarcoplasmic reticulum

B. Enhanced retrieval of Ca2+ by the sarcoplasmic reticulum

C. Failure to disengage tropomyosin and troponin from the myosin active sites

D. Absence of ATP preventing detachment of the myosin heads from actin

E. Increased lactic acid production

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A 5-year-old boy sustains a small tear in his gastrocnemius muscle when he is involved in a bicycle accident. Regeneration of the muscle will occur through which of the following mechanisms?

A. Dedifferentiation of muscle cells into myoblasts.

B. Differentiation of muscle satellite cells.

C. Fusion of damaged myofibers to form new myotubes.

D. Hyperplasia of existing muscle fibers.

E. Differentiation of fibroblasts to form myoblasts

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