Download Skeletal Muscle

EGBO ARUBE RUBY
14/MHS06/020
MBBS
200L
THE HISTOLOGY OF MUSCLE AS A TISSUE
A Tissue is a cellular organizational level intermediate between cells and a
complete organ. A tissue is an ensemble of similar cells from the same origin that
together carry out a specific function. There are four basic types of tissue namely:
Epithelial tissue, Nervous tissue, Connective tissue and Muscle tissue.
Muscle tissue is composed of cells differentiated for optimal use of contractility.
Microfilaments and associated proteins together generate the forces necessary
for cellular contraction, which drives movement within certain organs and the
body as a whole. Nearly all muscle cells are of mesodermal origin and they
differentiate mainly by a gradual process of cell lengthening with simultaneous
synthesis of myofibrillar proteins- actin and myosin.
The basis for motion mediated by muscle cells is the conversion of chemical
energy (ATP) into mechanical energy by the contractile apparatus of muscle cells
(which includes the actin and myosin proteins). The interaction of these two
proteins mediates the contraction of muscle cells.
The cytoplasm of muscle cells is called sarcoplasm (Gr. sarkos, flesh, + plasma,
thing formed) and the smooth ER is called sarcoplasmic reticulum. The
sarcolemma (sarkos + Gr. lemma, husk) is the cell membrane, or plasmalemma.
Three types of muscle tissue can be distinguished on the basis of morphologic and
functional characteristics and the structure of each type is adapted to its
physiologic role; they are
1. Skeletal Muscle
2. Smooth Muscle
3. Cardiac Muscle
A muscle tissue can either be voluntary or involuntary and/or striated or nonstriated.
1. Skeletal Muscle
Skeletal muscle is composed of bundles of very long, cylindrical,
multinucleated cells with diameters of 10–100 m that show cross-striations
(i.e they are striated). The Skeletal muscle is associated with the skeletal
system. The long oval nuclei are usually found at the periphery of the cell
under the cell membrane. This characteristic nuclear location is helpful in
discriminating skeletal muscle from cardiac and smooth muscle, both of
which have centrally located nuclei.
Their contraction is quick, forceful, and usually under voluntary control. It
is caused by the interaction of thin actin filaments and thick myosin
filaments whose molecular configuration allows them to slide upon one
another. The forces necessary for sliding are generated by weak
interactions in the bridges between actin and myosin.
Development of skeletal muscle.
Skeletal muscle begins to differentiate when mesenchymal cells called
myoblasts align and fuse together to make longer, multinucleated tubes
called myotubes. Myotubes synthesize the proteins to make up
myofilaments and gradually begin to show cross striations by light
microscopy. Myotubes continue differentiating to form functional
myofilaments and the nuclei are displaced against the sarcolemma. Part of
the myoblast population does not fuse and differentiate, but remains as a
group of mesenchymal cells called muscle satellite cells located on the
external surface of muscle fibers inside the developing external lamina.
Satellite cells proliferate and produce new muscle fibers following muscle
injury.
Development of skeletal muscle
Organization of skeletal muscle
The masses of fibers that make up the various types of muscle are arranged
in regular bundles surrounded by the epimysium, an external sheath of
dense connective tissue surrounding the entire muscle. From the
epimysium, thin septa of connective tissue extend inward, surrounding the
fascicles or bundles of fibers within a muscle. The connective tissue around
each fascicle is called the perimysium. Each muscle fiber is itself
surrounded by a more delicate connective tissue, the endomysium,
composed of a basal lamina synthesized by the multinucleated fibers
themselves as well as reticular fibers and fibroblasts. Within each fiber the
nuclei are displaced peripherally against the sarcolemma.
Muscle Fibers
As observed with the light microscope, longitudinally sectioned skeletal
muscle fibers show cross-striations of alternating light and dark bands. The
darker bands are called A bands (Anisotropic or birefringent in polarized
light); the lighter bands are called I bands (Isotropic, do not alter polarized
light). In the TEM each I band is seen to be bisected by a dark transverse
line, the Z line (Ger. Zwischenscheibe, between the discs). The sarcomere,
extends from Z line to Z line and is about 2.5 m long in resting muscle.
The A and I banding pattern in sarcomeres is due mainly to the regular
arrangement of two types of myofilaments—thick and thin—that lie
parallel to the long axis of the myofibrils in a symmetric pattern.
The thick filaments are 1.6 m long and 15 nm wide; they occupy the A band,
the central portion of the sarcomere. The thin filaments run between and
parallel to the thick filaments and have one end attached to the Z line. Thin
filaments are 1.0 m long and 8 nm wide. As a result of this arrangement,
the I bands consist of the portions of the thin filaments that do not overlap
the thick filaments (which is why they are lighter staining). The A bands are
composed mainly of thick filaments in addition to overlapping portions of
thin filaments. Close observation of the A band shows the presence of a
lighter zone in its center, the H zone, that corresponds to a region
consisting only of the rod-like portions of the myosin molecule with no thin
filaments present. Bisecting the H zone is the M line (Ger. Mitte, middle), a
region where lateral connections are made between adjacent thick
filaments. Major proteins present in the M line region are myomesin, a
myosin-binding protein which holds the thick filaments in place, and
creatine kinase, which catalyzes the transfer of phosphate groups from
phosphocreatine (a storage form of high-energy phosphate groups) to
adenosine diphosphate (ADP), thus helping to supply adenosine
triphosphate (ATP) for muscle contraction.
Thin and thick filaments overlap for some distance within the A band. As a
consequence, a cross section in the region of filament overlap shows each
thick filament surrounded by six thin filaments in the form of a hexagon.
Thin filaments are composed of F-actin, associated with tropomyosin,
which also forms a long fine polymer, and troponin, a globular complex of
three subunits. Thick filaments consist primarily of myosin. Myosin and
actin together represent 55% of the total protein of striated muscle.
F-actin consists of long filamentous polymers containing two strands of
globular (G-actin) monomers, 5.6 nm in diameter, twisted around each
other in a double helical formation. G-actin molecules are asymmetric and
polymerize to produce a filament with polarity. Each G-actin monomer
contains a binding site for myosin. Actin filaments, which are anchored
perpendicularly on the Z line by the actin-binding protein -actinin, exhibit
opposite polarity on each side of the line.
Transverse tubules are invaginations of the sarcolemma that penetrate
deeply into the muscle fiber around all myofibrils.
Structure of a Myofibril
Molecules composing thin and thick filaments.
The contractile proteins are the thin and thick myofilaments within
myofibrils.
i)
Each thin filament is composed of F-actin, tropomyosin, and troponin
complexes.
ii)
Each thick filament consists of many myosin heavy chain molecules
bundled together along their rod-like tails, with their heads exposed
and directed toward neighboring thin filaments.
iii)
Besides interacting with the neighboring thin filaments, thick
myofilament bundles are held in place by less well-characterized
myosinbinding proteins within the M line.
Each tropomyosin subunit is a long, thin molecule about 40 nm in length
containing two polypeptide chains, which assembles to form a long
polymer located in the groove between the two twisted actin strands.
Troponin is a complex of three subunits: TnT, which attaches to
tropomyosin; TnC, which binds calcium ions; and TnI, which inhibits the
actin-myosin interaction. Troponin complexes are attached at specific sites
at regular intervals along each tropomyosin molecule.
Myosin is a much larger complex (molecular mass ~500 kDa). Myosin can be
dissociated into two identical heavy chains and two pairs of light chains.
Myosin heavy chains are thin, rod-like molecules (150 nm long and 2–3 nm
thick) made up of two heavy chains twisted together as myosin tails. Small
globular projections at one end of each heavy chain form the heads, which
have ATP binding sites as well as the enzymatic capacity to hydrolyze ATP
(ATPase activity) and the ability to bind actin. The four light chains are
associated with the head. Several hundred myosin molecules are arranged
within each thick filament with their rodlike portions overlapping and their
globular heads directed toward either end.
Analysis of thin sections of striated muscle shows the presence of
crossbridges between thin and thick filaments. These bridges are formed by
the head of the myosin molecule plus a short part of its rodlike portion.
These bridges are involved in the conversion of chemical energy into
mechanical energy.
Thin and Thick Filaments
Muscle Fiber Types
Skeletal muscle cells are highly adapted for discontinuous production of
intense work through the release of chemical energy. Muscle fibers have
depots of energy to cope with bursts of activity. The most readily available
forms of energy are ATP and phosphocreatine, both of which are energyrich phosphate compounds. Chemical energy is also stored in glycogen
particles, which constitute about 0.5–1% of muscle weight. Muscle tissue
obtains energy as ATP and phosphocreatine from the aerobic metabolism
of fatty acids and glucose. Fatty acids are broken down to acetate by the
enzymes of -oxidation in the mitochondrial matrix. Acetate is then further
oxidized by the citric acid cycle, with the resulting energy being conserved
in the form of ATP. When skeletal muscles are subjected to a short-term
(sprint) exercise, they use anaerobic metabolism of glucose (coming mainly
from glycogen stores), producing lactate and causing an oxygen debt that is
repaid during the recovery period. The lactate formed during this type of
exercise is the cause of cramping and pain in skeletal muscles.
Skeletal muscle fibers of humans are classified into three types based on
their physiological, biochemical, and histochemical characteristics. All three
fiber types are normally found throughout most muscles.
1. Type I or slow, red oxidative fibers contain many mitochondria and
abundant myoglobin, a protein with iron groups that bind O2 and
produce a dark red color. Red fibers derive energy primarily from
aerobic oxidative phosphorylation of fatty acids and are adapted for
slow, continuous contractions over prolonged periods, as required for
example in the postural muscles of the back.
2. Type IIa or fast, intermediate oxidative-glycolytic fibers have many
mitochondria and much myoglobin, but also have considerable
glycogen. They utilize both oxidative metabolism and anaerobic
glycolysis and are intermediate between the other fiber types both in
color and in energy metabolism. They are adapted for rapid contractions
and short bursts of activity, such as those required for athletics.
3. Type IIb or fast, white glycolytic fibers have fewer mitochondria and
less myoglobin, but abundant glycogen, making them very pale in color.
They depend largely on glycolysis for energy and are adapted for rapid
contractions, but fatigue quickly. They are typically small muscles with a
relatively large number of neuromuscular junctions, such as the muscles
that move the eyes and digits.
Medical Application
The classification of fiber types in muscle biopsies has clinical significance
for the diagnosis of muscle diseases, or myopathies (myo + Gr. pathos,
suffering).
The differentiation of muscle into red, white, and intermediate fiber types
is controlled by the frequency of impulses from its motor innervations, and
fibers of a single motor unit are of the same type. Simple denervation of
muscle leads to fiber atrophy and paralysis.
2. Cardiac Muscle
Cardiac muscle also has cross-striations (i.e it is also striated) and is
composed of elongated, branched individual cells that lie parallel to each
other. Cardiac muscles are the muscles of the heart. At sites of end-to-end
contact are the intercalated disks, structures found only in cardiac muscle.
Contraction of cardiac muscle is involuntary, vigorous, and rhythmic.
During embryonic development, the mesoderm cells of the primitive heart
tube align into chainlike arrays. Rather than fusing into multinucleated
cells, as in the development of skeletal muscle fibers, cardiac muscle cells
form complex junctions between extended processes. Cells within a fiber
often branch and bind to cells in adjacent fibers. Consequently, the heart
consists of tightly knit bundles of cells, interwoven in a fashion that
provides for a characteristic wave of contraction that leads to a wringing
out of the heart ventricles.
Diagram of cardiac muscle cells indicates characteristic features of this
muscle type. The fibers consist of separate cells with interdigitating
processes where they are held together. These regions of contact are called
the intercalated discs, which cross an entire fiber between two cells. The
transverse regions of the steplike intercalated disc have abundant
desmosomes and other adherent junctions which hold the cells firmly
together. Longitudinal regions of these discs contain abundant gap
junctions, which form "electrical synapses" allowing contraction signals to
pass from cell to cell as a single wave. Cardiac muscle cells have central
nuclei and myofibrils that are less dense and organized than those of
skeletal muscle. Also the cells are often branched, allowing the muscle
fibers to interweave in a more complicated arrangement within fascicles
that produces an efficient contraction mechanism for emptying the heart.
Mature cardiac muscle cells are approximately 15 m in diameter and from
85 to 100 m in length. They exhibit a cross-striated banding pattern
comparable to that of skeletal muscle. Unlike multinucleated skeletal
muscle, however, each cardiac muscle cell possesses only one or two
centrally located pale-staining nuclei. Surrounding the muscle cells is a
delicate sheath of endomysium containing a rich capillary network.
A unique and distinguishing characteristic of cardiac muscle is the presence
of dark-staining transverse lines that cross the chains of cardiac cells at
irregular intervals. These intercalated discs represent the interface between
adjacent muscle cells where many junctional complexes are present.
Transverse regions of these steplike discs have many desmosomes and
fascia adherentes (which resemble the zonula adherentes between
epithelial cells) and together these serve to bind cardiac cells firmly
together to prevent their pulling apart under constant contractile activity.
The more longitudinal portions of each disc have multiple gap junctions,
which provide ionic continuity between adjacent cells. These act as
"electrical synapses" and allow cells of cardiac muscle to act as in a
multinucleated syncytium, with contraction signals passing in a wave from
cell to cell.
A few differences in structure exist between atrial and ventricular muscle.
The arrangement of myofilaments is the same in both, but atrial muscle has
markedly fewer T tubules, and the cells are somewhat smaller. Membranelimited granules, each about 0.2–0.3 m in diameter, are found at the poles
of atrial muscle nuclei and are associated with Golgi complexes in this
region. These granules release the peptide hormone atrial natriuretic factor
(ANF) which acts on target cells in the kidney to affect Na+ excretion and
water balance. The contractile cells of the heart's atria thus also serve an
endocrine function.
3. Smooth Muscle
Smooth muscle consists of collections of fusiform cells that do not show
striations. Their contraction process is slow and not subject to voluntary
control. Smooth muscle fibers are elongated, tapering, and nonstriated
cells, each of which is enclosed by a thin basal lamina and a fine network of
reticular fibers. The connective tissues serve to combine the forces
generated by each smooth muscle fiber into a concerted action, eg,
peristalsis in the intestine.
Concentrated near the nucleus of a smooth muscle are mitochondria,
polyribosomes, cisternae of rough ER, and the Golgi apparatus. Pinocytotic
vesicles are frequent near the cell surface.
A rudimentary sarcoplasmic reticulum is present in smooth muscle cells,
but T tubules are not. The characteristic contractile activity of smooth
muscle is related to the structure and organization of its actin and myosin
filaments, which do not exhibit the organization present in striated
muscles. In smooth muscle cells, bundles of thin and thick myofilaments
crisscross obliquely through the cell, forming a latticelike network. Smooth
muscle actin and myosin contract by a sliding filament mechanism similar
to that in striated muscles. However, myosin proteins are bundled
differently and the cross-bridges interact with fewer F-actin filaments.
The thin filaments of smooth muscle cells lack troponin complexes and
instead utilize calmodulin, a calcium-binding protein that is also involved in
the contraction of non-muscle cells. As in all muscle, an influx of Ca2+ is
involved in initiating contraction in smooth muscle cells. However in these
cells the Ca2+ calmodulin complex activates myosin light chain kinase
(MLCK), the enzyme that phosphorylates myosin, which is required for
myosin's interaction with F-actin. A number of hormones and other factors
affect the activity of MLCK and thus influence the degree of contraction of
smooth muscle cells.
Smooth muscle cells have an elaborate array of 10-nm intermediate
filaments. Desmin is the major intermediate filament protein in all smooth
muscles and vimentin is an additional component in vascular smooth
muscle. Both intermediate filaments and F-actin filaments insert into dense
bodies (Figure 10–20) which can be membrane-associated or cytoplasmic.
Dense bodies contain -actinin and are thus functionally similar to the Z discs
of striated and cardiac muscles. The attachments of thin and intermediate
filaments to the dense bodies helps transmit contractile force to adjacent
smooth muscle cells and their surrounding network of reticular fibers.
Contraction of smooth muscle is not under voluntary control, but is
regulated by autonomic nerves, certain hormones, and local physiological
conditions such as the degree of stretch.
Smooth muscle is divided into two subgroups; the single-unit (unitary) and
multiunit smooth muscle. Within single-unit cells, the whole bundle or
sheet contracts as a syncytium (i.e. a multinucleate mass of cytoplasm that
is not separated into cells). Multiunit smooth muscle tissues innervate
individual cells; as such, they allow for fine control and gradual responses,
much like motor unit recruitment in skeletal muscle. Unitary smooth
muscle is more common in which only a few cells are innervated but all
cells are interconnected by gap junctions. Gap junctions allow the stimulus
for contraction to spread as a synchronized wave among adjacent cells.
Smooth muscle lacks neuromuscular junctions like those in skeletal muscle.
Instead axonal swellings with synaptic vesicles simply lie in close contact
with the sarcolemma, with little or no specialized structure to the junctions.
Because smooth muscle is usually spontaneously active without nervous
stimuli, its nerve supply serves primarily to modify activity rather than
initiate it. Smooth muscle receives both adrenergic and cholinergic nerve
endings that act antagonistically, stimulating or depressing its activity. In
some organs, the cholinergic endings activate and the adrenergic nerves
depress; in others, the reverse occurs.
In addition to contractile activity, smooth muscle cells also synthesize
collagen, elastin, and proteoglycans, extracellular matrix (ECM)
components normally synthesized by fibroblasts.
A relaxed and contracted smooth muscle.