THE MUSCULAR SYSTEM

I. Overview of Muscular Tissue

A. Types of Muscular Tissue
1. Skeletal muscle tissue
- Skeletal muscle tissue is striated (Alternating light and dark protein bands).
- Works mainly in a voluntary manner; its activity can be consciously controlled by neurons (nerve cells).
2. Cardiac muscle tissue
- Forms most of the heart wall.
- Cardiac muscle is also striated, but its action is involuntary.
- The heart beats because it has a natural pacemaker that initiates each contraction. This built-in rhythm is
termed autorhythmicity.
3. Smooth muscle tissue
- Located in the walls of hollow internal structures (e.g. blood vessels, airways, most organs in the
abdominopelvic cavity, some found in the skin and hair follicles).
- It is nonstriated; referred to as smooth.
- Action of smooth muscle is usually involuntary.

B. Functions of Muscular Tissue

1. Producing body movement.
- Movements of the whole body such as walking and running, and localized movements such as nodding the
head as a result of muscular contractions that rely on the integrated functioning of skeletal muscles, bones,
and joints.
2. Stabilizing body positions.
- Skeletal muscle contractions stabilize joints and help maintain body positions, such as standing or sitting.
3. Storing and moving substances within the body.
- Sphincters, a ringlike bands of smooth muscle, help prevent outflow of the contents of a hollow organ.
- One example is the temporary storage of food in the stomach or urine in the urinary bladder is possible
because smooth muscle sphincters close off the outlets of these organs.
4. Generating heat.
- As muscular tissue contracts, it produces heat, a process known as thermogenesis. The heat generated by
muscle is used to maintain normal body temperature.
- Involuntary contractions of skeletal muscles, known as shivering, can increase the rate of heat production.

C. Properties of Muscular Tissue

1. Electrical excitability
- It is the ability to respond to certain stimuli by producing electrical signals called action potentials
(impulses). Action potentials in muscles are referred to as muscle action potentials; those in nerve cells
are called nerve action potentials.
2. Contractility
- It is the ability of muscular tissue to contract forcefully when stimulated by an action potential. When a
skeletal muscle contracts, it generates tension (force of contraction) while pulling on its attachment points.
3. Extensibility
- It is the ability of muscular tissue to stretch, within limits, without being damaged. The connective tissue
within the muscle limits the range of extensibility and keeps it within the contractile range of the muscle
cells.
4. Elasticity
- It is the ability of muscular tissue to return to its original length and shape after contraction or extension.

II. Skeletal Muscle Tissue

A. Connective Tissue Components
1. Fascia
- A dense sheet or broad band of irregular connective tissue that lines the body wall and limbs and
supports and surrounds muscles and other organs of the body.
- Holds muscles with similar functions together, allows free movement of muscles, carries nerves, blood
vessels, and lymphatic vessels, and, fills spaces between muscles.
- Three layers of connective tissue extend from the fascia to protect and strengthen skeletal muscle:
a. Epimysium
- Outermost layer of dense, irregular connective tissue.
- Surrounds the entire muscle.
 b. Perimysium
- Layer of dense, irregular connective tissue.
- Surrounds groups of 10 to 100 or more muscle fibers, separating them into bundles called
fascicles.
c. Endomysium
- Penetrates the interior of each fascicle, separates individual muscle fibers from one another.
- Mostly reticular fibers and thin sheath of areolar connective tissue.

B. Microscopic Anatomy of a Skeletal Muscle Fiber

1. Sarcolemma
- Plasma membrane of a muscle cell.
- Thousands of tiny invaginations of the sarcolemma, called transverse (T) tubules.
2. Transverse Tubules
- T tubules are open to the outside of the fiber and thus are filled with interstitial fluid.
- Muscle action potentials travel along the sarcolemma and through the T tubules, quickly spreading
throughout the muscle fiber.
- Arrangement ensures that an action potential excites all parts of the muscle fiber at essentially the same
instant.
3. Sarcoplasm
- The cytoplasm of a muscle fiber, it includes a substantial amount of glycogen.
- Contains a red-colored protein called myoglobin.
- Red-colored protein found only in muscles
- Binds oxygen molecules that diffuse into muscles fibers from interstitial fluid
- Releases oxygen when it is needed by the mitochondria for ATP production
4. Myofibrils
- The contractile organelles of skeletal muscle their prominent striations make the entire skeletal muscle fiber
appear striated.
5. Sarcoplasmic Reticulum
- Dilated end sacs of the sarcoplasmic reticulum called terminal cisterns butt against the T tubule from both
sides.
- A transverse tubule and the two terminal cisterns on either side of it form a triad.
6. Filaments
- May either be thick or thin.
- Thin filaments are 8 nm in diameter and 1–2 μm long, while thick filaments are 16 nm in
diameter and 1–2 μm long.
7. Sarcomere
- Basic functional unit of a myofibril.
- The thick and thin filaments overlap one another to a greater or lesser extent, depending on whether the muscle
is contracted, relaxed, or stretched.
- The darker middle part of the sarcomere is the A band, which extends the entire length of the thick filaments.

C. Muscle Proteins
 Myofibrils are built from three kinds of proteins:
1. Contractile proteins
- Generates force during contraction.

2 types:
a. Myosin: Thick filaments; functions as a motor protein in all three types of muscle tissue.
b. Actin: Thin filaments; point of attachment of myosin.
2. Regulatory proteins
- Help switch the contraction process on and off.
2 types:
a. Tropomyosin: Cover the myosin-binding sites on actin in a relaxed muscle.
b. Troponin: Binds to actin to facilitate actin-myosin binding which may cause muscle contraction.
3. Structural proteins
- Keeps the thick and thin filaments in the proper alignment, give the myofibril elasticity and extensibility, and
link the myofibrils to the sarcolemma and extracellular matrix.
4 types:
a. Titin
- Third most plentiful protein in skeletal muscle (after actin and myosin).
- Thereby helping stabilize the position of the thick filament.
b. Actinin
- Bind to actin molecules of the thin filament and to titin.
c. Myomesin
 - Form the M line; The M line proteins bind to titin and connect adjacent thick filaments to one
another.
d. Nebulin
- Long, nonelastic protein wrapped around the entire length of each thin filament. Helps anchor the
thin filaments to the Z discs and regulates the length of thin filaments during development.
e. Dystrophin
- A cytoskeletal protein that links thin filaments of the sarcomere to integral membrane proteins of
the sarcolemma.

III. Levels of Organization within a Skeletal Muscle

A. Skeletal Muscle
- Organ made up of fascicles that contain muscle fibers (cells), blood vessels, and nerves; wrapped in
epimysium.

B. Fascicle
- Bundle of muscle fibers wrapped in perimysium.

C. Muscle fiber (cell)

- Long cylindrical cell covered by endomysium and sarcolemma; contains sarcoplasm, myofibrils, many
peripherally located nuclei, mitochondrial transverse tubules, sarcoplasmic reticulum, and terminal cisterns.
The fiber has a striated appearance.

D. Myofibril
- Threadlike contractile elements within sarcoplasm of muscle fiber that extend entire length of fiber;
composed of filaments.

E. Filaments (myofilaments)
 - Contractile proteins within myofibrils that are of two types: thick filaments composed of myosin and thin fi
laments composed of actin, tropomyosin, and troponin; sliding of thin fi laments past thick fi laments
produces muscle shortening.

IV. Contraction and Relaxation of Skeletal Muscle Fibers

A. Contraction Cycle
- The contraction cycle consists of four steps:
 STEP 1: ATP hydrolysis. The myosin head includes an ATP-binding site and an ATPase, an enzyme
that hydrolyzes ATP into ADP (adenosine diphosphate) and a phosphate group. This hydrolysis
reaction reorients and energizes the myosin head. Notice that the products of ATP hydrolysis—ADP
and a phosphate group—are still attached to the myosin head.
 STEP 2: Attachment of myosin to actin to form cross-bridges. The energized myosin head attaches
to the myosin-binding site on actin and releases the previously hydrolyzed phosphate group. When the
myosin heads attach to actin during contraction, they are referred to as cross-bridges.
 STEP 3: Power stroke. After the cross-bridges form, the power stroke occurs. During the power
stroke, the site on the cross-bridge where ADP is still bound opens. As a result, the cross-bridge rotates
and releases the ADP. The cross-bridge generates force as it rotates toward the center of the sarcomere,
sliding the thin filament past the thick filament toward the M line.
 STEP 4: Detachment of myosin from actin. At the end of the power stroke, the cross-bridge remains
firmly attached to actin until it binds another molecule of ATP. As ATP binds to the ATP binding site
on the myosin head, the myosin head detaches from actin.

Figure 1. The contraction cycle. Sarcomeres exert force and shorten through repeated cycles during which the myosin
heads attach to actin (cross-bridges), rotate, and detach. During the power stroke of contraction, cross-bridges rotate and
move the thin filaments past the thick filaments toward the center of the sarcomere.

B. Length–Tension Relationship
- The length–tension relationship for skeletal muscle, which indicates how the forcefulness of muscle
contraction depends on the length of the sarcomeres within a muscle before contraction begins.
 At a sarcomere length of about 2.0–2.4 µm (which is very close to the resting length in most muscles),
the zone of overlap in each sarcomere is optimal, and the muscle fiber can develop maximum tension.
 Maximum tension (100%) occurs when the zone of overlap between a thick and thin filament extends
from the edge of the H zone to one end of a thick filament.
 As the sarcomeres of a muscle fiber are stretched to a longer length, the zone of overlap shortens, and
fewer myosin heads can make contact with thin filaments. Therefore, the tension the fiber can produce
decreases.
  When a skeletal muscle fiber is stretched to 170% of its optimal length, there is no overlap between the
thick and thin filaments. Because none of the myosin heads can bind to thin filaments, the muscle fiber
cannot contract, and tension is zero.
 As sarcomere lengths become increasingly shorter than the optimum, the tension that can develop again
decreases. This is because thick filaments crumple as they are compressed by the Z discs, resulting in
fewer myosin heads making contact with thin filaments.
 Normally, resting muscle fiber length is held very close to the optimum by firm attachments of skeletal
muscle to bones (via their tendons) and to other inelastic tissues.

Figure 2. Length–tension relationship in a skeletal muscle fiber. Maximum tension during contraction occurs when
the resting sarcomere length is 2.0–2.4 µm. A muscle fiber develops its greatest tension when there is an optimal zone of
overlap between thick and thin filaments.
 Figure 3. Summary of the events of contraction and relaxation in a skeletal muscle fiber.

V. Cardiac Muscle Tissue

- Consists of branched, striated fibers with usually only one centrally located nucleus (occasionally two). Attach
end to end by transverse thickenings of plasma membrane called intercalated discs which contain
desmosomes and gap junctions. Desmosomes strengthen tissue and hold fibers together during vigorous
contractions. Gap junctions provide route for quick conduction of electrical signals throughout the heart.
Involuntary control.
- It is located at the heart wall.
- As it contracts, it propels blood into the circulation; involuntary control.

VI. Smooth Muscle Tissue

- Consists of non-striated fibers. Smooth muscle fiber is a small spindle-shaped cell thickest in middle, tapering at
each end, and containing a single, centrally located nucleus. Gap junctions connect many individual fibers in
some smooth muscle tissue. Usually involuntary; can produce powerful contractions as many muscle fibers
 contract in unison. Where gap junctions are absent, such as iris of eye, smooth muscle fibers contract
individually, like skeletal muscle fibers.
- It is located at the iris of eyes; walls of hollow internal structures such as blood vessels, airways to lungs,
stomach, intestines, gallbladder, urinary bladder, and uterus.
- It propels substances or objects (foodstuffs, urine, a baby) along internal passageways; involuntary control.

VII. Regeneration of Muscular Tissue

- Because mature skeletal muscle fibers have lost the ability to undergo cell division, growth of skeletal muscle
after birth is due mainly to hypertrophy (the enlargement of existing cells, rather than to hyperplasia (an
increase in the number of fibers).
- Satellite cells divide slowly and fuse with existing fibers to assist both in muscle growth and in repair of
damaged fibers. Thus, skeletal muscle tissue can regenerate only to a limited extent.
- In addition, cardiac muscle fibers can undergo hypertrophy in response to increased workload (many athletes
have enlarged hearts).
- Smooth muscle tissue, like skeletal and cardiac muscle tissue, can undergo hypertrophy. In addition, certain
smooth muscle fibers, such as those in the uterus, retain their capacity for division and thus can grow by
hyperplasia.
- New smooth muscle fibers can arise from cells called pericytes, stem cells found in association with blood
capillaries and small veins. Smooth muscle fibers can also proliferate in certain pathological conditions, such as
occur in the development of atherosclerosis.

VIII. Development of Muscle Tissue

- Except for muscles such as those of the iris of the eyes and the arrector pili muscles attached to hairs, all
muscles of the body are derived from mesoderm.
- As the mesoderm develops, part of it becomes arranged in dense columns on either side of the developing
nervous system.
- Dense columns of mesoderm undergo segmentation into a series of cube-shaped structures called somites. The
first pair of somites appears on the 20th day of embryonic development. Eventually, 42 to 44 pairs of somites
are formed by the end of the fifth week.
- The number of somites can be correlated to the approximate age of the embryo.
- The cells of a somite differentiate into three regions:
a. Myotome: forms the skeletal muscles of the head, neck, and limbs; (2)
b. Dermatome: which forms the connective tissues, including the dermis of the skin;
c. Sclerotome: gives rise to the vertebrae.
- Cardiac muscle develops from mesodermal cells that migrate to and envelop the developing heart while it is still
in the form of endocardial heart tubes.
- Smooth muscle develops from mesodermal cells that migrate to and envelop the developing gastrointestinal
tract and viscera.
 Figure 4. Location and structure of somites, key structures in the development of the muscular system. Most
muscles are derived from mesoderm.

IX. Drugs Acting on the Musculoskeletal System

A. Drug Skeletal Muscle Relaxant
 Peripherally acting muscle relaxant
1. Drugs acting at NMJ
a. Depolarizing Blockers
 Succinylcholine
 Decametholium
b. Non-depolarizing blockers (competitive blockers)
b.1. Long Acting
 D-TC
 Pancuronium
 Doxacurium
 Pipecuronium
b.2.Intermediate Acting
 Vecuronnium
 Atraccurium
 Rocuronium
b.3. Short acting
Mivacurium
c. Others
 Botulium toxin A
2. Drug Directly acting on Skeletal Muscle
 Dantrolene
a. Centrally acting muscle relaxant
  Diazepam and other benzodiazepines
 Methocarbamol
 Chlorzoxone
 Tizanidine
 Baclofen
 Gabapentin
B. Neuromuscular Blocking agent
 Nondepolarizing Blocking Agents
1. Curare Alkaloids
 (+)-tubocurarine
 Metocurarine
2. Synthetic Compounds
a. Tetrahydroisoquinoline based agents
 Atracurium
 Micavarium
 Doxacurium
b. Steroid-based agents
 Pancuronium
 Vecuronium
 Pipecurium
 Rocuronium
 Depolarizing Blocking Agents
 Succinylcholine

Sources:
Derrickson, B., Tortora, G. (2014). Principles of Anatomy and Physiology. Quad Graphics/Versailles.
Seeley et al. (2017). Seeley’s Anatomy and Physiology. Georgia State University Press.