Chapter 10: Muscle Tissue

Muscle Tissue – has cells that contract.

➢ Actin microfilaments and proteins generate force for contraction which drives movement.
➢ Mesodermal origin

3 Types
1. Skeletal Muscle – bundles of very long multinucleated cells with cross-striations

➢ Contraction is quick, forceful, and voluntary

2. Cardiac Muscle – cross-striations and has elongated, often branched cells bound to intercalated discs

➢ Intercalated Discs – unique to cardiac muscle.

➢ Contraction is involuntary, vigorous, and rhythmic

3. Smooth Muscle – collection of fusiform cells which lack striations

➢ Contraction is involuntary and slow

Skeletal Muscle Cross-striations Strong Voluntary

Cardiac Muscle Cross-striations Strong Involuntary
Smooth Muscle Lack striations Weak Involuntary

Contraction – caused by sliding interaction of myosin

filaments along actin filaments.

➢ Forces necessary for sliding are made by other

proteins.

Sarcoplasm – cytoplasm of muscle cells

Sarcoplasmic Reticulum – smooth ER

Sarcolemma – muscle cell membrane and external Hypertrophy – increased cell volume
lamina Hyperplasia – tissue growth by increase in
the number of cells

> SKELETAL MUSCLE

Consists of muscle fibers

Muscle fibers – long, cylindrical multinucleated cells.

Mesenchymal Myoblasts – during embryonic muscle development, it fuses

to form myotubes with many nuclei.
 ➢ Elongated nuclei found under the sarcolemma (unique to skeletal muscle fibers/cells)

Satellite Cells – reserve progenitor cells, adjacent to most fivers of differentiated skeletal muscle.

Organization of a Skeletal Muscle

Thin connective tissue surrounds and organize contractile
fibers in all types of muscle. Seen well in skeletal.

Supportive layers in large peripheral nerves:

1. Epimysium – external sheath of dense irregular

connective tissue, surrounds the entire muscle.
a. Septa – extends inward, carrying larger nerves,
blood vessels, and lymphatics of the muscle.
2. Perimysium – thin connective tissue layer that
surrounds a fascicle
a. Fascicle – bundle of muscle fibers, makes up a
functional unit where fibers work together.
b. Nerves, blood vessels, lymphatics supply each
fascicle.
3. Endomysium – located within the fascicles, surrounds
the external lamina of individual muscle fibers.
a. Capillaries bring O2 to the muscle fibers.

Collagen – transmit the mechanical forces

Myotendinous Junctions – tough connective tissue of a tendon

that joins the muscle to bone, skin, or another muscle.

Organization Within Muscle Fibers

Myofibrils – long cylindrical filament bundles that run parallel to the long axis of the fiber.

➢ A bands – DARK bands

➢ I bands – LIGHT bands, do not overlap the thick filaments in the A bands.
➢ Z disc – bisects I band by a dark transverse line.
➢ Sarcomere – repetitive subunit of the contractile apparatus and extends from Z disc to Z disc.

Myofilaments – thick and thin regular arrangement that causes the A and I banding pattern in
sarcomeres.

➢ Have myosin (thick) and f-actin (thin) organized in a symmetric pattern

Myosin (1.6µm long 15nm wide) – thick filaments that occupy the A band at the middle region of the
sarcomere.
 ➢ Large complexes with two identical heavy chains and two pairs of light chains.
➢ Heavy chains – thin, rodlike motor proteins twisted as myosin tails.
➢ Light chains – four chains that form a head at one end of each heavy chain.
o Binds both actins, forming bridges between the thick and thin filaments, and ATP,
catalyzing energy release.

Actin (1.0µm long and 8nm wide) – run between the thick filaments.

➢ Each G-actin monomer contains a binding site for myosin

➢ Anchored perpendicularly on the Z disc

Two Regulatory Proteins:

1. Tropomyosin – coil of two polypeptide chains in the groove between two twisted actin strands.
2. Troponin – complex of three subunits:
a. TnT – attaches to tropomyosin
b. TnC – binds Ca2+
c. TnI – regulates actin-myosin interaction

I Bands

α-actin – actin-binding protein, exhibits opposite polarity on each side of the Z disc.

Titin – accessory protein in I bands, largest protein in the body

➢ Supports the thick myofilaments and connects them to the Z disc.

Nebulin – large accessory protein, binds each thin myofilament laterally.

➢ Helps anchor them to α-actin

➢ Specifies the length of the actin polymers during myogenesis.

A Bands

Contains the thick filaments and overlapping portions of thin filaments.

H zone – light zone in its center, a region with only rodlike portions of the myosin molecule and no thin
filaments.

M line – inside the H zone, contains myomesin

Myomesin – holds thick filaments in place and creatine kinase

Creatine Kinase – enzyme that catalyzes transfer of phosphate groups form phosphocreatine helping
supply ATP for muscle contraction.

Phosphocreatine – storage form of high-energy phosphate groups

Myosin & Actin – represent over half of the total protein in striated muscle.

➢ Cause of the striated appearance of the skeletal muscle.

Sarcoplasmic Reticulum & Transverse Tubule System
Sarcoplasmic Reticulum – smooth ER of skeletal muscle fibers.

➢ Contain pumps and other proteins for Ca2+ sequestration and surrounds the myofibrils.
➢ Calcium release from cisternae of sarcoplasmic reticulum through Ca2+ channels to muscle fiber.
➢ Simultaneous release of calcium and contraction of all myofibrils

Transverse or T-tubules – tubular infoldings of the sarcolemma

➢ Ling fingerlike invagination that penetrates into the sarcoplasm and encircle each myofibril near
the aligned A- and I- band boundaries of sarcomeres.

Terminal Cisternae – adjacent to each T-tubule.

➢ Triad – complex of T-tubule with two terminal cisternae

➢ Allows depolarization of the sarcolemma in a T-tubule to affect the sarcoplasmic reticulum and
release calcium ions into cytoplasm.
➢ Calcium initiates contraction of sarcomeres.

Mechanism of Contraction
Contraction – occurs due to the overlapping of thin and thick filaments of each sarcomere as they slide
past one another.

1. Neuromuscular Junction (NMJ) – action potential

2. Action potential arrives to trigger calcium release.
a. Resting muscle, myosin heads cannot bind actin because sites are blocked by troponin-
tropomyosin complex on the F-actin filaments.
3. Calcium ions bind to troponin
4. Change in shape and moving tropomyosin on the F-actin to expose myosin-binding active sites.
5. Binding actin produce a change or pivot in the myosins
a. Energy from hydrolysis of ATP
b. Continued presence of calcium and ATP, attach-pivot-detach repeats about 50
milliseconds.
c. Shortens the sarcomere and contract the muscle
6. Pulling thin filaments farther into the A band to the Z disc.
7. When neural impulse stops tropomyosin covers the myosin-binding sites on actin.
8. Filaments passively slide back and sarcomeres return to their relaxed length.

Rigor mortis – rigidity of skeletal muscles that occurs as mitochondrial activity stops after death.
Innervation
Myelinated (inside perimysium) → Unmyelinated terminal twigs → Endomysium → Synapses → Muscle
Fibers

Schwann cells – enclose small axon branches and cover their points of contact with the muscle cells.
 ➢ External lamina fuses with sarcolemma

Motor end plates (MEPs) – axonal branch forms dilated termination within a trough on the muscle cell
surface, part of the synapses termed the neuromuscular junctions.

Axon terminal have:

➢ Mitochondria
➢ Several synaptic vesicles
o Acetylcholine – neurotransmitter

Synaptic cleft – between the axon and muscle

Junctional folds – adjacent to the synaptic cleft, where sarcolemma is thrown in.

➢ Provides greater postsynaptic surface area and more transmembrane acetylcholine receptors.

Nerve action potential → MEP → Acetylcholine liberated from axon terminal → Diffuses to the cleft →
binds receptors in the folded sarcolemma

Acetylcholine receptor – has nonselective cation channel that opens upon neurotransmitter binding.

➢ Allows influx of cations, depolarizing the sarcolemma, and producing muscle action potential.

Acetylcholinesterase – extracellular enzyme that removes free neurotransmitter from the synaptic cleft.

➢ Prevents prolonged contact of the transmitter with its receptors.

Muscle action potential → sarcolemma → T-tubules → sarcoplasm

➢ Triads – depolarization signal release calcium from terminal cisterns of sarcoplasmic reticulum,
initiating contraction cycle

Innervation (single muscle fibers by single motor neurons) – provide precise control of muscle activity.

➢ Occurs in extraocular muscles for eye movements

Motor Unit – single axon and all muscle fibers branch and
make up this

Individual striated muscle fibers – do not show graded

contraction, contract either all the

To vary contraction – muscle fibers don’t contract at the

same time.

Large muscles:
Myasthenia gravis – autoimmune disorder
involving circulating antibodies against ➢ Coarser movements
proteins of acetylcholine receptors.
 ➢ Have motor axons that branch profusely and innervate 100 or more muscle fibers.
➢ Composed of many motor units
➢ Firing single motor axon generate tension proportional to the number of muscle fiber it
innervates.
➢ Number of motor units and their variable size control the intensity and precision of muscle
contraction.

Muscle Spindles & Tendon Organs

Proprioceptors – sensory receptors in striated muscle and myotendinous junctions

➢ Provides the central nervous system (CNS) data from the musculoskeletal system.
Muscle spindles – detectors of the muscle fascicles (2mm long and 0.1mm wide)

➢ Encapsulated by modified perimysium with intrafusal fibers

➢ Intrafusal fibers – concentric layers of flattened cells with interstitial fluid and a few thin muscle
fibers filled with nuclei.
➢ Have many sensory nerve axons.
➢ Detects changes in length (distension) of the surrounding (extrafusal) muscle fibers caused by
body movements.
➢ Sensory nerves relay info to the spinal cord.

Golgi Tendon Organs – smaller encapsulated structures that enclose sensory axons penetrating among
the collagen bundles at the myotendinous junction.

➢ Detect changes in tension within tendons produced by muscle contraction.

➢ Act to inhibit motor nerve activity if tension becomes excessive.
➢ Help regulate the amount of effort required to perform movements that call for variable
amounts of muscular force.

Skeletal Muscle Fiber Types

Dystrophin – large actin-binding protein in the
sarcolemma of skeletal muscle fiber.
Functional organization of myofibrils.
Duchenne Muscular Dystrophy – mutations of
the dystrophin can lead to defective linkages
of cytoskeleton and ECM. Muscle contraction
can disrupt the weak linkages causing atrophy
(decrease) of muscle fibers.
Skeletal muscles in:
➢ eyes and eyelids – need to contract rapidly.
➢ For posture – maintain tension for longer
periods while resisting fatigue
Possible due to varied expression in muscle fibers
contractile or regulatory protein isoforms.

Different types of fibers identified:

➢ Maximal rate of contraction (fast or slow fibers)

o Due to myosin isoforms with different maximal rates of ATP hydrolysis.
o Histochemical staining – use to identify fast and slow ATPases
➢ Major pathway for ATP synthesis (oxidative phosphorylation or glycolysis)

➢ Densities of surrounding capillaries

➢ Number of mitochondria
➢ Levels of glycogen and myoglobin

Myoglobin – globular sarcoplasmic protein same to hemoglobin which has iron atoms and allows
oxygen storage
3 Major Types of Fiber Diversity

1. Slow oxidative – slow contractions over long periods without fatigue

a. Many mitochondria
b. Many surrounding capillaries
c. Much myoglobin
d. Dark or red in color
2. Fast glycolytic – rapid short-term contraction
a. Few mitochondria or capillaries
b. Depending on anaerobic metabolism of glucose from glycogen
c. Rapid contraction → rapid fatigues as lactic acid from glycolysis accumulates
d. White
3. Fast oxidative-glycolytic – intermediate between the others.

Metabolic type – determined by the rate of impulse conduction along its motor nerve supply.

Determining fiber types in needle biopsies of skeletal muscle helps diagnosis of:

➢ Myopathies
➢ motor neuron diseases
➢ other causes of atrophy

> CARDIAC MUSCLE

Embryonic Development – mesenchymal cells around the primitive heart tube
align rather than fusing.

Cardiac Muscle – cells form complex junctions between interdigitating

processes.

➢ Cells often branch and join with cells in adjacent fibers.

 ➢ Mature: 15-30µm in diameter and 85-120µm long
➢ Has striated banding pattern
➢ Each cell has only one nucleus and centrally located
➢ Endomysium – delicate sheath with rich capillary
network that surrounds the muscle cells.
➢ Perimysium – separates bundles and layers of muscle
fibers
➢ Cardiac skeleton – large masses of fibrous connective
tissues
Ischemia – tissue damage due to lack
of oxygen in heart diseases.

Heart – consists of tightly knit bundles of cells interwoven in spiraling layers

➢ Wave contraction that resembles wringing out of the heart ventricles.

➢ Muscle of heart ventricles is much thicker than the atria
➢ Ventricular muscle T-tubules fibers are well-developed.
o Large lumens
o Penetrates the sarcoplasm in the vicinity of the myofibrils’ Z disc.
➢ Atrial muscle T-tubules are much smaller or entirely absent

Intercalated Discs – unique characteristic of cardiac muscle

➢ Transverse lines that cross the fibers at irregular intervals

➢ Where myocardial cells join
➢ Represents the interfaces between adjacent cells and consist of many junctional complexes.
➢ Has many desmosomes and fascia adherens junctions – provide strong intercellular adhesion
during constant contract.

Less abundant region of intercalated disc run parallel to the myofibrils and are filled with gap junctions

➢ Provide ionic continuity between cells.

➢ “electrical synapses”
➢ Promotes rapid muscle conduction through many cardiac muscle cells simultaneously and
contraction of many adjacent cells as a unit.

Same contractile apparatus as the skeletal muscle.

➢ Mitochondria 40% of cell volume (higher than slow oxidative skeletal muscle)
➢ Fatty acids – major fuel of the heart
o Stored as triglycerides in small lipid droplets.
➢ Glycogen granules
➢ Perinuclear lipofuscin pigment granules

Sarcoplasmic Reticulum – less well-organized

➢ Junctions between terminal cisterns and T-tubules involve only one structure of each type
forming dyads.
Contractions – intrinsic and spontaneous

➢ Impulses for rhythmic contraction (heartbeat) – are initiated, regulated, and coordinated locally
by nodes.
➢ All-or-none
➢ Rate of contraction is modified by autonomic innervation at the nodes.
➢ Sympathetic nerve supply accelerating
➢ Parasympathetic supply decreases the frequency of the impulses

Secretory Granules – 0.2-0.3µm in diameter, found near atrial muscle nuclei

➢ Associated with small Golgi complexes.

➢ Release the peptide hormone atrial natriuretic factor (ANF)
➢ ANF – target cells in the kidney to affect sodium excretion and water balance
➢ Contractile of cells of the heart’s atria is endocrine function.

> SMOOTH MUSCLE

Specialized for slow, steady contraction under the influence of autonomic nerves
and various hormones.

Visceral Muscle – fibers of smooth muscle

➢ Elongated, tapering and unstriated cells

➢ Enclosed by an external lamina and type I and III collagen fibers
comprising the endomysium

Major component of:

➢ Blood Vessels
➢ Digestive
➢ Respiratory
➢ Urinary
➢ Reproductive tracts

Cells – length from 20µm in small blood vessels to 500µm in the pregnant uterus.

➢ Only largest profile contains a nucleus

➢ Linked by many gap junctions
➢ Concentrated near the nucleus are:
o Mitochondria
o Polyribosomes
o RER
o Vesicles of a Golgi apparatus
➢ In the surface are caveolae
o Small plasmalemma invaginations
o Compartmentalize various signaling components
o Contains major ion channels that control calcium release that initiates contraction.
Fibers – have rudimentary sarcoplasmic reticulum but lack T-tubules

➢ Unnecessary in smaller tapering cells with many gap junctions

Contractile activity – generated by myofibrillar arrays of actin and myosin

➢ Thin and thick myofilaments crisscross the sarcoplasm obliquely.

➢ Myosin filaments – less regular arrangement among the thin filaments and fewer crossbridges
➢ Actin filaments – not associated with troponin and tropomyosin using instead:
o Calmodulin
o Myosin light-chain kinase (MLCK) – calcium sensitive
o to produce contraction
➢ Contraction mechanism is similar to striated muscle
➢ INVOLUNTARY
o Fibers lack neuromuscular junctions
➢ Stimulated by autonomic nerves
➢ Gastrointestinal tract – controlled by various paracrine secretions
➢ Uterus – oxytocin from the pituitary gland

Actin myofilaments → cytoplasmic and dense bodies (have α-actin, functions same to Z discs) →
intermediate filaments

Intermediate filaments – 10nm, composed of desmin

➢ Attach to the dense bodies

Submembranous dense bodies – have cadherins of desmosomes linking adjacent smooth muscle cells

➢ Serve as points for transmitting contractile force in cells and adjacent cells

Endomysium and other connective tissue – help combine the force generated by the smooth muscle
fibers into a concerted action

➢ Peristalsis (wave-like muscle contractions that move food through the digestive tract) in the
intestine

Autonomic nerves Axons – periodic swellings or varicosities is close with muscle fibers

➢ Synaptic vesicles release neurotransmitter (acetylcholine or norepinephrine)

➢ Diffuses and binds receptors in the sarcolemmae of many muscle cells.
➢ No specialized structure to junctions
➢ Stimulation is propagated to distant fibers via gap junctions allow smooth muscle cells to
contract.

Other activity of smooth muscle cells:

➢ Supplement fibroblast activity

➢ Synthesizing collagen
➢ Elastin
 ➢ Proteoglycans (major influence on ECM)
➢ Active synthesis of ECM may reflect less specialization for strong contractions, same function in
myofibroblasts and pericytes.

Leiomyomas – benign tumors in smooth

muscle fibers.

Fibroids – leiomyomas in the uterus.

> REGENERATION OF MUSCLE TISSUE

Skeletal Muscles – limited regeneration

➢ Satellite cells – mesenchymal, source of regeneration

o Inside the external lamina of each muscle fiber.
o Inactive reserve myoblasts which persist after muscle differentiation.
o After injury, is activated, fusing to form new skeletal muscle fibers.
o Cell hypertrophy – muscle growth after extensive exercise, fuse with existing fibers.

Cardiac Muscles – very little regenerative capacity beyond early childhood

➢ No satellite cells
➢ Defects or damage are generally replaced by proliferating fibroblasts and growth of connective
tissue forming myocardial scars

Smooth Muscles – more active regenerative response

➢ Simpler, smaller, mononucleated cells

➢ After injury, viable smooth muscle cells undergo mitosis to replace damaged tissue
➢ Pericytes from walls of small blood vessels participate in the repair of vascular smooth muscle.