(Midterm) HISTOLOGY / MUSCLE TISSUE
>Visceral Striated Muscle
MUSCLE TISSUE
= responsible for movement of the body and its
parts and for changes in the size and shape of internal
organs.
= characterized by aggregates of specialized,
elongated cells arranged in parallel array that have the
primary role of contraction.
Myofilament Interaction
= responsible for muscle contraction
TWO TYPES OF MYOFILAMENTS:
- occupy the bulk of the cytoplasm
>Thin Filaments (6-8 nm in diameter, 1.5 um long)
= composed primarily of the protein ACTIN
*each thin filament of fibrous actin (F-actin) is a polymer formed
from globular actin molecules (G-actin)*
>Thick Filaments (~15 nm in diameter, 1.5 um long)
= composed of the protein MYOSIN II
= consists of 200 300 myosin II molecules
*tail portion long, rod shaped that aggregates in a regular
parallel but staggered array
*head portions project out in a regular helical pattern
Sarcoplasm
= cytoplasm of the muscle cells
*ACTIN and MYOSIN II present in most other cell types where
they play a role in cellular activities such cytokinesis, exocytosis
and cell migration.
TWO PRINCIPAL TYPES OF MUSCLES(according to the
appearance of contractile cells):
>Striated Muscle
= cells exhibit cross striations at the light microscope level
>Smooth Muscle
= cells do not exhibit cross striations
= restricted to the viscera and vascular system, the arrector pili
muscles of the skin and intrinsic muscles of the eyes *myosin-
containing myofilaments in smooth muscle are highly labile*
SUBCLASSIFICATION OF STRIATED MUSCLE(base on
location):
>Skeletal Muscle
= attached to the bones
= responsible for movement of the axial and appendicular
skeleton
= responsible for the maintenance of body position and posture
*extraocular muscles skeletal muscles of the eye that
provide precise eye movement
= morphologically identical to skeletal muscle but is restricted to
the soft tissues (tongue, pharynx, lumbar part of the diaphragm
and upper part of the esophagus)
= play essential role in speech, breathing and swallowing
>Cardiac Muscle
= found in the wall of the heart and in the base of the large
veins that empty into the heart
SKELETAL MUSCLE
- Each muscle cell is a multinucleated syncytium.
- Consists of striated muscle fibers held together by
connective tissue
Myoblast
= small individual muscle cells that form a muscle
fiber during its development Muscle fiber = Skeletal
muscle cell
Sarcolemma = Skeletal plasma membrane, its
external lamina and surrounding reticular
lamina
*Nuclei of a skeletal muscle fiber are located in the cytoplasm
immediately beneath the plasma membrane (sarcolemma)*
CONNECTIVE TISSUE ASSOCIATED WITH
MUSCLE(according to relationship with muscle fibers):
>Endomysium
= delicate layer of reticular fibers that immediately surrounds
individual muscle fibers
= with only small-diameter blood vessels and finest neuronal
branches, running parallel to the muscle fibers
>Perimysium
= thicker connective tissue layer that surrounds a group of
fibers to form a bundle or fascicle = with larger blood
vessels and nerves
>Epimysium
= sheath of dense connective tissue that surrounds a collection
of fascicles that constitutes the muscle = with major vascular
and nerve supply
Fascicles
= functional units of muscle fibers that tend to
work together to perform a specific function
*Connective tissue that surrounds both individual muscle fibers
and bundles of muscle fibers is essential for force
transduction.*
*At the end of the muscle, connective tissue continues as a
tendon or some other collagen fibers that attaches the muscle
usually to the bone.*
THREE TYPES OF SKELETAL MUSCLE FIBERS(by color
in vivo):
>Red >White >Intermediate
(Midterm) HISTOLOGY / MUSCLE TISSUE
Succinic dehydrogenase &Nicotinamide adenine
dinucleotide-tetrazolium (NADH-TR) = histochemical
reactions based on oxidative enzyme activity
= confirm the observation seen in fresh tissue
= reveal special types of skeletal muscle fibers
*Skeletal muscle fibers are characterized by speed of
contraction, enzymatic velocity and metabolic activity.*
BASIS OF CURRENT CLASSIFICATION OF SKELETAL
MUSCLE FIBERS:
>Contractile Speed determines how fast the fiber can
contract and relax
> Enzymatic Velocity (myosin ATPase) determines the rate
at which the enzyme is capable of breaking down ATP
molecules during contraction cycle
>Metabolic Profile indicates the capacity for ATP production
by oxidative phosphorylation of glycolysis.
Myoglobin
= an oxygen-binding protein that closely
resembles hemoglobin found in erythrocytes and
occurs in varying amounts in muscle fibers
= provides a ready source of oxygen for muscle
metabolism
THREE TYPES OF SKELETAL MUSCLE FIBERS:
>Type I Fibers/Slow Oxidative Fibers(red fibers) = small fibers
that appear red in fresh specimens and contain many
mitochondria and large amounts of myoglobin and
cytochrome complexes
= slow-twitch, fatigue resistant motor units
= have a great resistance to fatigue but generate less tension
than other fibers
= their myosin ATPase reaction velocity is the slowest of all the
fiber types.
= typically found in the limb muscles of mammals and in the
breast muscle of migrating birds
= (more importantly) they are the principal fibers of the long
muscles of the back in humanswhere they are particularly
adapted to the long, slow contraction needed to maintain erect
posture
= make up the muscles of high-endurance athletes such as
marathon runners
*TWITCH single brief contraction of the muscle*
>Type IIa Fibers/Fast Oxidative Glycolytic Fibers
(intermediate fibers)
= the intermediate fibers seen in fresh tissue = medium size
with many mitochondria and a high myoglobin
content
= contain large amounts of glycogen and are capable of
anaerobic glycolysis
= fast-twitch, fatigue resistant motor units that generate high
peak muscle tension
= for athletes that include 400-and 800-m sprinters,
middledistance swimmers and hockey players
>Type IIb Fibers/Fat Glycolytic Fibers
= large fibers that appear light pink in fresh specimens and
contain less myoglobin and fewer mitochondria that type I and
type IIa fibers
= low level of oxidative enzymes but exhibit high anaerobic
enzyme activity and store a considerable amount of glycogen
= fast-twitch, fatigue prone motor units
= generate high peak muscle tension
= myosin ATPase velocity of this type is the fastest of all the fiber
types
= fatigue rapidly due to production of lactic acid
= adapted for rapid contraction and precise, fine movements =
constitute fibers of the extraocular muscles and the muscles that
control the movements of the digits
= have greater number of neuromuscular junctions allowing
more precise neuronal control of movements in those muscles
= for short-distance sprinters, weight lifters and other field
athletes
*MYOFIBRILS AND MYOFILAMENTS*
Myofibril
= structural and functional subunit of the muscle
fiber
= longitudinally arrayed structural subunits
= visible in favorable histologic preparations and are
best seen in cross-sections of muscle fibers
(stippled appearance)
= extend the entire length of the muscle cell
= composed of bundles of myofilaments
Myofilaments
= individual filamentous polymers of myosin II (thick
filaments) and actin and its associated proteins (thin
filaments)
= actual contractile elements of striated muscle
= bundles of which make up the myofibril
surrounded by ER
Sarcoplasmic Reticulum
= well-developed smooth-surfaced endoplasmic reticulum that
surround the myofibril = forms a highly organized tubular
network around the contractile elements in all striated muscle
cells *Mitochondria and glycogen deposits are located between
the
myofibrils in association with the sER.*
Cross-striations
= principal histologic feature of striated muscle =
evident in H&E-stained preparations of
longitudinal sections of muscle fibers = (in unstained
preparations), examined with a phase contrast or
polarizing microscope, which they appear as alternating
light (I band) and dark (A band) bands
A band
= birefringent(they alter polarized light in two planes)
(Midterm) HISTOLOGY / MUSCLE TISSUE
= being doubly refractive are anisotropic
*H band (Hell-light) a less dense or light region that bisects
the A band; the bare zone in the myosin filament
I band
= monorefringent(they do not alter the plane of polarized light)
= they are isotropic
*Z line/Z disc (Zwischenscheibe-b/w discs) a dense line that
bisects the I band
*M line (Mitte-middle) a narrow dense line that bisects the
light H band
- best demonstrated in electron micrographs
Sarcomere (2-3 um in relaxed mammalian muscle)
= functional unit of the myofibril
= basic contractile unit of striated muscle
= a portion of myofibril between two adjacent Z lines
*Arrangement of thick and thin filaments gives rise to the
density differences that produce the cross-striations of the
myofibril.*
Myosin-containing thick filaments about 1.5 um long and
are restricted to the central portion of the sarcomere
Thin filaments attach to the Z line and extend into the A
band to the edge of the H band
*In a longitudinal section of a sarcomere, the Z line appears as
a zigzag structure with matrix material the Z matrix, bisecting
the zigzag.*
*The Z line and its matrix material anchor the thin filaments from
adjacent sarcomeres to the angles of the zigzag by the actin-
binding protein -actinin.*
PRIMARY PROTEINS IN THE CONTRACTILE
APPARATUS OF THIN FILAMENTS:
>F-actin
= a double-stranded helix formed from the polymerization of G-
actin (small, 42-kilodalton moleule) = they are polar
= the plus end of each filament is bound to the Z line by
actinin
= the minus end extends toward the M line and is protected by
an actin-capping protein
>Tropomyosin (64-kilodalton protein)
= consists a double helix of two polypeptides
= it forms filaments that run in the groove between the F-actin
molecules in the thin filament
= (in resting muscle), together with its regulatory protein
(troponin complex) mask the myosin-binding site on the actin
molecule
>Troponin
= consist of THREE GLOBULAR SUBUNITS:
Troponin-C (TnC)= smallest subunit of the troponin
complex (18 kilodaltons)
= it binds Ca2+, the essential step in the initiation of
contraction
Troponin-T (TnT) = a 30-kilodalton subunit = binds to
tropomyosin, anchoring thr troponin complex
Troponin-I (TnI) = a 30-kilodalton subunit = binds to
actin, thus inhibiting actin-myosin
interaction
PRIMARY PROTEIN IN THE CONTRACTILE
APPARATUS OF THICK FILAMENTS:
>Myosin II
= a 510-kilodalton protein
= composed of two polypeptide heavy chains (222-kilodaltons
each) and four light chains
= TWO TYPES OF LIGHT CHAINS:
Essential Light Chains (18 kilodaltons)
Regulatory Light Chains (22 kilodaltons)
*The phosphorylation by myosin light chain kinase of the
regulatory light chain initiates contraction in smooth muscles.*
Myosin molecules(in striated muscles)
= aggregate tail to tail to form bipolar thick myosin filaments
= the rod-shaped segments overlap so that the globular heads
project from the thick filament
ACCESSORY PROTEINS:
Accessory Proteins
= maintain precise alignment of thin and thick filaments
= essential in regulating the spacing, attachment, and
alignment of the myofilaments
= structural protein components of skeletal muscle fibrils that
constitute less than 25% of the total
protein of the muscle fiber
>Titin (2,500-kilodalton)
= large protein that forms an elastic lattice that anchors thick
filaments in the Z lines
= two spring-like portions of the protein adjacent to the thin
filaments
= help stabilize the centering of the myosin-containing thick
filament, preventing excessive stretching of the sarcomere
> Actinin (190-kilodalton)
= short, bipolar, rod-shaped actin binding protein
= bundles with filaments into parallel arrays and anchors them
at the Z line
>Nebulin (600-kilodalton)
= elongated, inelastic protein
= attached to the Z lines and runs parallel to the thin filaments
= helps the -actinin anchor thin filaments to Z lines = thought
to regulate the length of thin filaments during muscle
(Midterm) HISTOLOGY / MUSCLE TISSUE

development 1. Attachment
The myosin head is tightly bound to the actin
>Tropomodulin (~40-kilodalton) molecule of the thin filament
= small actin-binding protein that is attached to the free portion ATP is absent. (arrangement known as
of the thin filament = actin-capping protein RIGOR CONFIGURATION)
= maintains and regulates the length of the sarcomeric actin
Ends with the binding of ATP to the myosin
filament
head.
= variation of this affect the length-tension relationship during
Rigor mortis- muscular stiffening and rigidity
muscle contraction and therefore influence the physiologic
properties of the muscle >Desmin (53-kilodalton) that begins at the moment of death caused
= type of intermediate filament by lack of ATP.
= forms a lattice that surrounds the sarcomere at the level of the
Z lines, attaching them to one another and to the plasma 2. Release
membrane, thus forming stabilizing cross-links between The myosin head is uncoupled from the thin
neighboring myofibrils filament due to the binding of ATP to the
myosin head.
>Myomesin (185-kilodalton) 3. Bending
= a myosin-binding protein The myosin head advances a short distance
= holds thick filaments in register at the M line in relation to thin filament (bending), caused
by hydrolysis of ATP
>C protein (140-150-kilodalton) (ATP Adenosine diphosphate and
= one of the possible several myosin-binding proteins = serves inorganic phosphate)
the same function as myomesin and forms several Both products (ADP and inorganic
distinct transverse stripes on either side of the M line phosphate) remain bound to the myosin head
Linear displacement of the myosin head
>Dystrophin (472-kilodalton) relative to the thin filament is 5nm
= a large protein which is thought to link laminin = resides in the 4. Force Generation
external lamina of the muscle cell, to actin filaments The myosin head releases
= encoded on the X chromosome which explains why only boys inorganic phosphate and the power
suffer from Duchennes muscular dystrophy *Duchennes stroke occurs.
muscular dystrophy a genetic condition associated with
Effects of release
progressive muscular weakness due to absence of dystrophin
Increase binding affinity between the
protein
myosin head and its new attachment
*To maintain the efficiency and speed of muscle contraction, site
both thin and thick filaments in each myofibril must be aligned The myosin head generates force as it
precisely and kept at an optimal distance from one another.* returns to its original unbent position
Power stroke of the cycle- forced
*When a muscle contracts, each sarcomere shortensand movement of the thin filament along the thick
becomes thicker, but the myofilaments remain the same filament, as the myosin head straightens
length.* ADP is lost from the myosin head
5. Reattachment
During the CONTRACTION:
The myosin head binds tightly to a new actin
- the sarcomere and I band shortens molecule of the thin filament.
- the A band remains the same length (Rigor Configuration) And the cycle can
- the H band narrows repeat.
- thin filaments penetrate the H band during contraction
Antiparallel Arrangement -Myosin head are arranged as
*To maintain the myofilaments at a constant length, the mirror images on either side of the H band.
shortening of the sarcomere must be caused by an increase in
the overlap of the thick and thin filaments.* *The movement of myosin head pulls the thin filaments into the
A band, thus shortening the sarcomere.
Contraction Cycle

Involves in shortening of a muscle that move the thin

filament along the thick filament. Regulation of Contraction
The 5 Stages of Contraction Cycle
Involves the following:

1. Ca2+ - must be available for the reaction between

actin and myosin.
(Midterm) HISTOLOGY / MUSCLE TISSUE

Removed after contraction *Resting concentration of Ca2+ is restored in the cytosol in less
Rapid delivery and removal of Ca2+- is than milliseconds
accomplished by sarcoplasmic reticulum and
transverse tubular system.
2. Sarcoplasmic Reticulum arranged as series of
networks around the myofibrils
Each network extends form one A-I junction
to the next A-I junction within a sarcomere. Motor Innervation
Terminal cisternae- slightly more regular
ringlike channel, forms at the junction Neuromuscular Junction contact made by the terminal
between A and I bands. branches of the axon with the muscle fiber
ContainsGated Ca2+ release channels Neurilemal (Schwann cell) - covers thin portion of myelin
to release Ca2+ to the sarcoplasm sheath and terminal ends of axon.
Mitochondria and glycogen granules
involved in providing energy for the reactions Motor unit- neuron along with specific muscle fibers
involve in contraction
3. Transverse tubular system or T system consist of *Muscle capable of the most delicate movements have the
T tubule (invaginations of the plasma membrane) fewest muscle fibers per motor neuron in their motor units.
T tubule located between adjacent terminal
cisternae at the A-I junctions Innervation- necessary for muscle cells to maintain their
Voltage-sensor proteins structural integrity.
depolarization-sensitive
membrane channels, activated Tissue Atrophy- nerve supply to a muscle is disrupted;
when the plasma membrane thinning of the muscle and its cell
depolarizes.

*Triad- complex of T tubule and two adjacent terminal

cisternae Sensory Innervation

Proprioreceptors

Encapsulated sensory receptors in muscles and

Initiation of the Muscle Contraction tendons
Part of the somatic sensory
The depolarization of the T-tubule membrane triggers the
Provides information about the degree of stretching
release of Ca2+ from the terminal cisternae to initiate muscle
and tension in a muscle.
contraction.
Muscle Spindle
Events leading to contraction of skeletal muscle
Specialized stretch receptor located within the skeletal
1. Nerve impulse travelling along the axon of a motor
muscle
neuron arrives at the neuromuscular junction
2. The nerve impulse prompts the release of acetylcholine Consist of two types of modified muscle fibers
into the synaptic cleft that binds into ACh-gate Na+ surrounded by internal capsule
channels causing local depolarization *Fluid-filled space- separates the internal capsule
3. Voltage-gated Na+ channels open, Na+ enters the cell from an outer external capsule.
A. Spindle cells
4. General Depolarization spreads
a. Nuclear bag fiber-contains an
5. Voltage sensor proteins in the plasma membrane of T
aggregation of nuclei in an expanded
tubules change their conformation.
midregion
6. At the muscle triads, the T tubules are in close contact
b. Nuclear chain fiber has many nuclei
with the lateral enlargements of the sarcoplasmic
arranged inn chain
reticulum, where gated Ca2+-release channels are
B. Neuron terminals
activated by conformational changes of voltage-sensor
proteins Transmits information about the degree of stretching
7. Ca2+ rapidly released from the sarcoplasmic reticulum in a muscle
into the sarcoplasm Sensory (afferent, Ia) nerve fibers- carry
information from the muscle spindle
8. Ca2+ binds to the TnC portion of the troponin complex
o Spindle cells receive motor innervation
9. The contraction cycle is initiated, and Ca2+ is returned to
from the spinal cord and brain via -
the terminal cisternae of the sarcoplasmic reticulum. motor efferent nerve fibers
Ca2+--activated ATPase pump - transports Ca2+ back into the Sensory (afferent, Ib) nerve fibers monitor
muscle tension within an optimal range
terminal cisternae
(Midterm) HISTOLOGY / MUSCLE TISSUE
o Golgi tendon organs
encapsulated receptors found in the
tendons of muscle and respond to
increased tension of the cell.
Development, Repair, Healing and Renewal
Myoblast- derived from a self-renewing population of
multipotential myogenic stem cells
Myogenic stem cells originate in the embryo from
a. Unsegmented paraxial mesoderm (cranial muscle
progenitors) or
b. Segmented mesoderm of somites (epaxial and
hypaxial muscle progenitors)
MyoD transcription factor plays a key role in activation of
muscle-specific gene expressions and differentiation of all
skeletal muscle lineages.
Myostatin gene- expression of this result to a balancing effect
on skeletal muscle development, which leads to synthesis of
myostatin.
Myostatin- exerts an inhibitory effect on muscle growth and
differentiation.
Skeletal muscle progenitors
A. Early myoblasts responsible for formation of
primary myotubes
Primary myotubes
Chainlike structures that extend between
tendons of the developing muscle.
Formed by nearly synchronous fusion of
early myoblasts.
B. Late myoblasts give rise to secondary myotubes
Secondary myotubes
Formed in the innervated zone of
developing muscle
Continue to form by sequential fusion of
myoblasts
Characterized by a smaller diameter,
more widely space nuclei,
and increased number of
myofilaments.
Satellite cells - Myogenic precursors of muscle cells
Responsible for the skeletal muscles ability to
regenerate, but their regenerative capacity is limited.
Normally quiescent and do not express myogenic
regulatory factors.
After injury, they proliferate and give rise to new
myoblasts
When External lamina remain intact- myoblasts
fuse within the external lamina to form myotubes,
which then mature to a new fiber
When External Lamina disrupted- fibroblasts repair
the injured site, with subsequent scar tissue formation.
Muscular dystrophies- characterized by progressive
degeneration of skeletal muscle fibers, which places a constant
demand on the satellite cells to replace the degenerated fibers.
CARDIAC MUSCLE
has the same types and arrangement of contractile
filaments as skeletal muscle
cells and the fibers they form exhibit cross-striations
evident in routine histologic sections intercalated
discs:
-densely staining cross-bands exhibited by cardiac
muscle fibers that cross the fibers in a linear fashion
or frequently in a way that resembles the risers of a
stairway
-represent highly specialized attachment sites
between adjacent cells (linear cell-to-cell attachment);
thus, results in fibers of variable length
consists of numerous cylindrical cells arranged end to
end
some cardiac muscle cells in a fiber may join with two
or more cells through intercalated discs; thus, creating
a branched fiber
Structure
The cardiac muscle nucleus lies in the center of the cell.
this is one feature that helps distinguish them from
multinucleated skeletal muscle fibers
transmission electron microscope (TEM) reveals that
the myofibrils of cardiac muscle separate to pass
around the nucleus; thus, outlining a biconical
juxtanuclear region (rich in mitochondria and
contains the Golgi apparatus, lipofuscin pigment
granules, and glycogen) in which the cell organelles
are concentrated
atrial granules
-found in the atria of the heart, measuring 0.3-0.4um
in diameter, are also concentrated in the juxtanuclear
cytoplasm
-contain two polypeptide hormones; both hormones
are diuretics, affecting urinary excretion of sodium,
inhibit rennin secretion by the kidney, inhibit
aldosterone secretion by the adrenal gland, inhibit
contractions of vascular smooth muscle 1. atrial
natriuretic factor (ANF) (L. natrium, sodium) 2. brain
natriuretic factor (BNF) *in congestive heart failure,
levels of circulating BNF increase
Numerous large mitochondria and glycogen stores are
adjacent to each myofibril.
cardiac muscle cells are characterized by large
mitochondria that are densely packed between the
myofibrils
these large mitochondria often extend the full length of
a sarcomere and contain numerous, closely packed
cristae
concentration of glycogen granules are also located
between the myofibrils
glycogen granules (structures that store energy) and
mitochondria (structures that release and recapture
energy) are located adjacent to the myofibrils that use
the energy to drive contraction The intercalated
discs represent junctions between cardiac muscle
cells.
(Midterm) HISTOLOGY / MUSCLE TISSUE
intercalated disc
-represents the attachment site between cardiac
muscle cells
-appears as a densely staining linear structure that is
oriented transversely to the muscle fiber -consists of
short segments arranged in a steplike fashion
when the site of intercalated disc is
examined with the TEM, the densely
staining structures seen in the light
microscope can be attributed to the
presence of transverse component
(that crosses the fibers at a right angle
to the myofibrils, analogous to the risers
of the stairway)
a lateral component (not visible in the
light microscope, analogous to the steps
of the stairway) occupies a series of
surfaces perpendicular to the transverse
component and lies parallel to the
myofibrils
both components of the intercalated disc
contain specialized cell-to-cell junctions
between adjoining cardiac muscle cells
1. fascia adherens (adhering junction)
major constituent of the transverse
component of the intercalated disc
responsible for its staining in routine
H&E preparations
holds the cardiac muscle cells at their
ends to form the functional cardiac
muscle fibers
always appears as a transverse
boundary between the cardiac muscle
cells
TEM reveals an intercellular space
between the adjacent cells that is filled
with electron-dense material resembling
the material found in the zonula
adherens of the epithelia
serves as the site at which the thin
filaments in the terminal sarcomere
anchor onto the plasma membrane (in
this way, the fascia adherens is
functionally similar to the epithelial
zonula adherens, where actin filaments
of the terminal web are also anchored)
2. maculae adherentes (desmosomes)
bind the individual muscle cells to one
another
help prevent the cells from pulling apart
under the strain of regular repetitive
contractions
reinforce the fascia adherens and are
found in both the transverse and lateral
components of the intercalated discs
3. gap junctions (communicating junctions)
constitute the major structural element of
the lateral component of the intercalated
disc
provide ionic continuity between
adjacent cardiac muscle cells; thus,
allowing informational macromolecules
to pass from cell to cell (this exchange
permits cardiac muscle fibers to behave
as a synctium while retaining cellular
integrity and individuality
the position of these gap junctions on
the lateral surfaces of the intercalated
disc protects them from the forces
generated during contraction
The sER in cardiac muscle cells is organized into a single
network along the sarcomere, extending from Z line Z line.
the sER in cardiac muscle is:
- not as well organized as that of skeletal muscle -
does not separate bundles of myofilaments into
discrete myofibrils
the T tubules in cardiac muscle penetrate into the
myofilament bundles at the level of the Z line,
between the ends of the sER networks (1 T tubule per
sarcomere)
small terminal cisternae of the sER are in close
proximity to the T tubules to form a diad at the level of
the Z line
the external lamina adheres to the invaginated plasma
membrane of the T tubule as it penetrates into the
cytoplasm of the muscle cell the T tubules are:
-larger and more numerous in cardiac ventricular
muscle than in skeletal muscle -less numerous in cardiac
atrial muscle Passage of Ca2+ from the lumen of the T
tubule to the sarcoplasm of a cardiac muscle cell is
essential to initiate the contraction cycle.
depolarization of the T tubule membrane activates
voltage-sensor proteins, which are similar in
structure and function to Ca2+ channels
in contrast to skeletal muscle, long-lasting
depolarization in cardiac muscle activates these
sensors and prompts their slow conformation change
into functional Ca2+ channels; thus, in the first stage of
the cardiac muscle contraction cycle, Ca2+ from the
lumen of the T tubule is transported to the sarcoplasm
of cardiac muscle, which opens gated Ca2+ release
channels in adjacent terminal sacs of the
sarcoplasmic reticulum (calcium-triggered calcium
release mechanism, causes a massive and rapid
release of additional Ca2+ that initiates subsequent
steps of the contraction cycle)
the longer-lasting membrane depolarization and
activation of voltage-sensitive Ca2+ channels in the
wall of the T tubule account for an approximately
200-millisecond delay from the start of a
depolarization in a cardiac muscle twitch (difference
between initiation of cardiac and skeletal muscle
contractions)
Cardiac muscle cells exhibit an intrinsic spontaneous
rhythmic contraction.
evident in embryonic cardiac muscle cells as well as
in cardiac muscle cells in tissue cultures cardiac
conducting cells:
-specialized, modified cardiac muscle cells that locally
regulate, coordinate, and initiate the heartbeat -
organized into nodes and highly specialized
conducting fibers called Purkinje fibers that generate
and rapidly transmit the contractile impulse to various
parts of the myocardium in a precise sequence
both parasympathetic and sympathetic nerve fibers
terminate in the nodes:
(Midterm) HISTOLOGY / MUSCLE TISSUE
-sympathetic stimulation accelerates the heartbeat by
increasing the frequency of impulses to the cardiac
conducting cells
-parasympathetic stimulation slows down the
heartbeat by decreasing the frequency of the
impulses
*the impulses carried by these nerves do not initiate
contraction but only modify the rate of intrinsic cardiac
muscle contraction by their effect at the nodes
Injury and Repair
a localized injury that results to death of cells is
repaired by replacement with fibrous connective tissue
(cardiac function is lost at the site of the injury)
this pattern of injury and repair is seen in nonfatal
myocardial infarction (MI)
-confirmation of suspected MI can be made through
the detection of specific markers in the blood -these
markers are the structural subunits TnI and TnT of the
cardiac troponin complex, usually released into the
blood stream within 3-12 hours after an MI -TnI levels
remain elevated for up to 2 weeks from the time of the
initial injury; thus, it is regarded as an excellent
marker for diagnosing MI that has recently occurred
Mature cardiac muscle cells are able to divide.
through studies concerning hearts removed from
individuals who had received transplants, it was
revealed that nuclei can undergo mitosis (0.1%)
suggests that damaged cells can potentially be
replaced
SMOOTH MUSCLE
generally occurs as bundles or sheets of elongated
fusiform cells with finely tapered ends
fibers (cells), range in length from 20um in the walls
of small blood vessels to about 200um in the wall of
the intestine, may be as large as 500um in the wall of
the uterus during pregnancy
interconnected by gap junctions (specialized
communication junctions between the cells, allowing
passage of small molecules or ions from cell to cell
and provide communication links that regulate
contraction of the entire bundle or sheet of smooth
muscle)
smooth muscle cytoplasm stains rather evenly with
eosin in routine H&E preparations (because of actin
and myosin concentrations)
nuclei are located at the center of the cell and often
have a corkscrew appearance in longitudinal sections
in the noncontracted cells, the nucleus appears as an
elongated structure with tapering ends, lying in the
center axis of the cell
when the nucleus is included in a cross section of a
smooth muscle fiber, it appears as a round or circular
profile whether the cell is contracted or relaxed
TEM shows that most of the cytoplasmic organells are
concentrated at each end of the nucleus (numerous
mitochondria, some cisternae of the rER, free
ribosomes, glycogen granules, small Golgi apparatus)
Structure
Smooth muscle cells possess a contractile apparatus
of thin and thick filaments and a cytoskeleton of
desmin and vimentin intermediate filaments.
the remaining sarcoplasm is filled with thin
filaments (form a part of the contractile
apparatus)
thick myosin filaments are scattered throughout
the sarcoplasm of a smooth muscle cell
(extremely labile, tend to be lost during tissue
preparation, but are demonsrated with TEM using
special techniques of preparation)
cytoplasmic densities or dense bodies
where the thin filaments are attached to, visible
among the filaments, distributed throughout the
sarcoplasm in a network of intermediate filaments
containing the protein desmin
intermediate filaments are part of the
cytoskeleton of the cell
vascular smooth muscles contain vimentin
filaments
components of the contractile apparatus in
smooth muscle cells
1. thin filaments
contain actin (the smooth muscle
isoform of tropomyosin, involved in
the forcegenerating interaction with
myosin II molecules)
contain two smooth muscle-specific
proteins (actin-binding proteins that
block the myosin-binding site, Ca2+
dependent and is also controlled by
the phophorylation of myosin
heads)
-caldesmon (120-150 kilodaltons
-calponin (34 kilodaltons)
no troponin is associated with
smooth muscle tropomyosin
the tropomyosin position on the
actin filament is regulated by
phosphorylation of myosin heads
2. thick filaments
differ slightly from those found in
skeletal muscle
contain myosin II
composed of two polypeptide heavy
chains and four light chains
the polarity of the myosin head is
the same along the entire length of
one side of the filament and the
opposite on the opposite side
(sidepolar myosin filament, with
no
central bare zone)
3. myosin light chain kinase (MLCK)
130-150 kilodalton
initiates the contraction cycle after
its activation by Ca2+ calmodulin
complex
4. calmodulin
17 kilodalton Ca2+ binding protein
related to the TnC found in skeletal
muscle, which regulates the
intracellular concentration of Ca2+
a Ca2+-calmodulin complex binds
to MLCK to activate this enzyme
(Midterm) HISTOLOGY / MUSCLE TISSUE
5. a-actinin
31 kilodalton
provides structural components to dense bodies
Dense bodies provide an attachment site for thin filaments
and intermediate filaments.
dense bodies contain a variety of attachment plaque
proteins, including a-actinin, which anchors both thin
filaments and intermediate filaments either directly or
indirectly to the sarcolemma
Contraction in smooth muscles is initiated by a variety of
impulses, including mechanical, electrical, and chemical
stimuli.
1. mechanical impulses
passive stretching of vascular smooth muscle,
activate mechanosensitive ion channels, leading to
initiation of spontaneous muscle contraction
(myogenic reflex)
2. electrical depolarizations
release of neurotransmitters acetylcholine and
norepinephrine
causes opening of voltage-sensitive Ca2+ channels
3. chemical stimuli
such as those elicited by angiotensin II, vasopressin,
or thromboxane A2, leading to muscle contraction
use second-messenger pathways (inositol
1,4,5trisphosphate (IP3), G-protein-coupled, nitric
oxide
(NO)-cGMP pathways)
Smooth muscle cells lack a T system.
presence of invaginations of the cell membrane that
resemble caveolae
ATP-dependent calcium plumps removes Ca2+
from the sarcoplasm and resequestered in the sER of
delivered to the extracellular matrix Contraction of
smooth muscle is regulated by the
Ca2+calmodulin-myosin light chain kinase system.
an increase in Ca2+ concentration stimulates a
myosin light chain kinase (MLCK) to phosphorylate
one of the two regulatory light chains of the myosin
molecule
the Ca2+ binds to calmodulin to form the
Ca2+calmodulin complex, which in turn binds to
MLCK to activate the phosphorylation reaction The
force of smooth muscle contraction may be
maintained for long periods in a latch state.
this latch state of smooth muscle contraction occurs
after the initial Ca2+ dependent myosin
phosphorylation
comparable to rigor mortis in striated muscle
Functional Aspects of Smooth Muscle Smooth
muscle is specialized for slow, prolonged
contraction.
exhibits a spontaneous contractile activity in the
absence of stimuli
usually regulated by post synaptic neurons of the
autonomic nervous system (ANS)
the enteric division is the primary source of nerves to
the muscular layers
although Ca2+ enters the cytoplasm during
depolarization by voltage-gated Ca2+ channels, some
Ca2+ channels, called ligand-gated Ca2+ channels,
are activated by hormones via their secondmessenger
pathways
Nerve terminals in smooth muscle are observed only in the
connective tissue adjacent to the muscle cells.
nerve fibers pass through the connective tissue within
the bundles of smooth muscle cells; enlargements in
the passing nerve fiber, or bouton en passant, occur
adjacent to the muscle cells to be innervated
smooth muscle cells make contact with neighboring
cells by gap junctions (nexus) Smooth muscle
cells also secrete connective tissue matrix.
rER and Golgi apparatus in the perinuclear zone
synthesize both type IV (basal lamina) collagen and
type II (reticular) collagen, as well as elastin,
proteoglycans, and multiadhesive glycoproteins
smooth muscle cells are surrounded by an external
lamina except at the junctions
Renewal, Repair, and Differentiation
Smooth muscle cells are capable of dividing to maintain or
increase their number.
differentiation of smooth muscle progenitor cells
is regulated by a variety of intracellular and
environmental stimuli, and developing muscles exhibit
a wide range of different phenotypes at different
stages of their development
serum response factor (RF), a member of the
MADS-box transcription factor family, has been shown
to regulate most smooth muscle differentiation
genes
myofibroblasts developed morphologic and
functional characteristics of smooth muscle cells in
fibroblasts of healing wounds
myoepithelial cell epithelial cells (sweat glands,
salivary glands, iris,) that acquired the characteristics
of smooth muscle cells
myoid cells of the testis have a contractile function
in the seminiferous tubules
cells of the perineurium a concentric layer of
connective tissue that surrounds groups of nerve
fibers and partitions peripheral nerves into distinct
fascicles, function as contractile cells as well as
transport barrier cells