*

* Contractility is property exhibited, in varying degree, by

nearly all cells.
* In muscle, this ability to convert chemical energy into
mechanical work has become highly developed.
* The locomotion of animals, the beating of their hearts, and the
movements of the stomach and intestine depend on three types
of muscle, each specialized for the kind of force required.
* The types of muscle are:
* smooth muscle
* skeletal muscle
* cardiac muscle.
 Skeletal muscle

Smooth muscle

Cardiac muscle
* The contraction of smooth muscle is a slow and is not subject to voluntary
control.
* The smooth muscle that generates movement in the viscera is controlled by
the autonomic nervous system.

* Contraction of skeletal muscle is rapid and under voluntary control.

* Skeletal muscle is activated by nerves of the cerebrospinal system.

* Contraction of cardiac muscle is forceful, rhythmic, and involuntary.

* Cardiac msucle is endowed with an intrinsic mechanism for generating
rhythmic contractions but receives additional input from the cerebrospinal
nervous system that influences the frequency of hearbeat.
*
* Smooth muscle forms a major portion of the wall of the
alimentary tract, from the middle of the esophagus to the
sphincter of the anus.
* Smooth muscle provides the motive force for mixing the
ingested food with digestive enzymes and for its propulsion
through the tract.
* Circumferentially oriented smooth muscle also occurs in the
walls of blood vessels and controls their caliber. It forms the
wall of the oviducts and uterus and is found in many other sites
in the body.

*
*Smooth muscle is made up of long fusiform (spindle-
shaped) cells with an elongated nucleus situated in
their wider central portion.

* They vary greatly in length, ranging from 20 um in small

blood vessels to 500 um in the pregnant uterus.
*Each smooth muscle cell is enveloped by a thin external
lamina, resembling the basal lamina of epithelia.

* Outside of this, there is a network of reticular fibers that bind

the cellular units together so that their contraction produces a
coordinated force. Neighboring cells are in contact only at gap
junctions, which provide the cell to cell communication
necessary for integrated contraction throughout the layer of
smooth muscle.
*Contraction of smooth muscle is relatively slow,
but it can be sustained for long periods.
*The cells can shorten to one-quarter of their resting
length and can generate a force, per cross-sectional
area, comparable to that of striated msucle, while
consuming far less energy.
*Contraction is believed to involve a sliding of the actin
filaments with respect to the myosin filaments that
results in a shortening of the filament bundles.

*
*However, a sliding mechanism of shortening is more
difficult to validate in smooth muscle than in striated
muscle.
*Myosin can interact with actin only if its light chain is
phophorylated.

*Smooth-muscle contraction is initiated by an influx of

calcium which binds to a calcium-bidning protein,
calmodulin.
* The calcium-calmodulin complex binds to myosin light-chain
kinase, activating this enzyme, which catalyzes the
phosphorylation of myosin light chains, enabling them to
interact with actin filaments and cause contraction.

*
*Smooth muscle differs in its
mode of activation in different
organs.

*Intestinal smooth muscle, an

example of unitary smooth
muscle, has an autorhythmicity.
Intrinsically generated stimuli are
conducted, via gap junctions,
throughout a large area of smooth
muscle that contracts in unison, and
waves of contraction (peristalsis)
then sweep along the intestine to
advance its contents.
* The type of smooth muscle in large arteries, in the ducts of
the male reproductive tract, and in the ciliary body of the
eye is designated multiunit smooth muscle.

* In muscle of this kind,there is little evidence of impulse conduction

from fiber to fiber via gap junctions.
* Instead, each fiber is innervated, and contraction is more rapid
than in unitary smooth muscle. Adrenergic and cholinergic nerves to
smooth muscle of this type act antagonistically.
*
*The units of organization of skeletal, or striated, muscle,
are not individual cells, but are long, cylindrical,
multinucleate syncytia, formed by fusion of multiple
myoblasts during embryonic development.
* Muscle fibers, 0.1 mm in diameter and several centimeters in
length, are arranged in bundles (fasicles) large enough to be
visible with the naked eye.

*
* The muscle, as a whole, is surrounded by a thin layer of dense
connecitive tissue forming the epimysium.
* Thin, branching connective tissue septa extend inward from the
epimysium and envelop each of the fasicles of muscle fibers.
These consitute the perimysium.
* A delicate network of reticular fibers around the individual
muscle fibers is the endomysium.

* This delicate network binds the contractile units together but

permits some motion between them.
Epimysium Perimysium
Endomysium
*The plasma membrane of skeletal and cardiac muscle
fibers has traditionally been called the sarcolemma, and
their cytoplasm is referred to as the sarcoplasm.
* The sarcolemma of each muscle fiber is coated with a thin amorphous
layer, the external lamina, that resembles the basal lamina of epithelia
but is thinner.

* The inner surface of the sarcolemma bears a thin layer of a 400-kDa

protein, dystrophin, that is not found in other cells.

* Its is believed to provide the membrane with an internal reinforcement

against the stresses developed in muscle contraction, relaxation, and
stretching, but it may have other functions yet to be discovered.
* Under the light microscope, muscle fibers have a closely
spaced cross-striation which is the basis for the term
“striated muscle,” commonly used to distinguish
skeletal and cardiac muscle from smooth msucle
* Within each muscle fiber, the thousands of contractile
myofiblrils are also cross-banded, with their bands
normally in register - this accounts for the cross-striation of
the fiber as a whole.
*The column of myofibrils in the sarcoplasm occupies the
greater part of the cross section of a muscle fiber,
displacing its many nuclei to the perphery.
= nuclei are flattened against the sarcolemma, their long
elleptical profiles are regularly spaced along the length of the
fiber.
= their exact number cannot be specified, but in a fiber
several centimiters in legth, they would number in the hundreds.
= their peripheral location is helpful in distinguishing
skeletal muscle from cardiac muscle – the nuclei are located in
the center of the fiber

*All of the common organelles are present in the

sarcoplasm.
*A small Golgi complex is associated with one pole of
many of the nuclei.

* Long mitochondria are found in the juxtanuclear sarcoplasm

and are also deployed in longitudinal rows between bundles of
myofibrils, here they provide the energy for contraciton.

*Lipid droplets are found in small numbers among the

organelles at the poles of the nuclei, a glycogen particles
are distributed throughout the sarcoplasm.
* In addition to these microscopically visible components, the
sarcoplasm contains myoglobin in solution. This oxygen-
binding protein is largely responsible for the brown color of
muscle. Oxygen dissociates from myoglobin, as required, and
becomes available for oxidative reactions.
* In transverse sections of striated msucle, the myofibrils
are resobled as fine dots, either uniformly distributed or
aggreagated in polygonal areas, that were formerly
called the fields of Cohnheim.
* In longitudinal sections, dark bands alternate with
relatively light bands
* When viewed with the polarizing microscope, the dark
bands are anistrophic and are therefore designated the
A-bands, whereas the light bands are isotropic and are
called I-bands.
Light bands
I-Bands

Dark bands
A-Bands
The relative length of the bands depends on the state of
contraction of the muscle.
* The I-bands are very short during contraction and longer in
relaxation.
* The length of the A-bands remains constant in all phases of
contraction.
* Each I-band is bisected by a narrow transverse line, the Z-line,
or Z-disk.
* The segments between successive Z-lines are called the
sarcomeres.
*each sarcomere includes an A-band and half of the two
contiguous I-bands.
*a paler-staining H-band in the middle of the A-band,
with a thin M-band, or M-line traversing its center.

* myofibrils are seen to be made up of myofilaments of

two kinds: thin actin filaments and thicker myosin
filaments .
= Myosin filaments are the major constituent of the A-band
= 1.5 um in length and 15 nm in diameter
= arranged parallel, with a space of about 45nm
between them.
*Actin filaments are the dominant component of the
I-band, and they extend for a variable distance into
the A-band, interdigitating with the myosin filaments.
* Information on the substructure of the thick filaments has been
obtained by mechanical dissociation of isolated filaments.
* Each filament yields about 350 myosin molecules.
* The actin-binding property of the heads of the myosin molecules is
essential for muscle contraction.
* Isolated thin filaments have a beaded
appearance at high magnicifation.
* They arise by polymerization of globular
monomers of G-actin, 5.6 nm in diameter.
* The polymers, F-actin, form two helically
entwined strands in which each gyre of the
helix is about 36 nm in length.
* Associated with the actin filaments
are long molecules of
tropomyosin arranged end-to-end in the grooves between the
helically entwined F-actin chains.
* Bound to each molecule of tropomyosin is a complex of three
troponin peptide designated:
*Tn-T binds the complex to tropomyosin.
*Tn-C has a binding site for the calcium that initiates contraction,
*Tn-I inhibits the binding of the myosin heads to actin in the resting
muscle.

* These submicroscopic components of the actin filaments have key

roles in the mechanism of muscle contraction
* A recently discovered muscle protein called titin is the largest
protein known.
* It is a single chain of nearly 27,000 amino acids with a molecular
weight of about 3 million.
* Its molecules are about 1 um long and span the distance between the
M-line and the Z-disk.
* The elastic properties of the titin molecules are thought to
be responsible for the ability of a muscle to spring back to
resting length after being stretched.
* ultrastructural studies of the
myofibrils have led to a widely
accepted sliding filament
hypothesis to explain striated-
muscle contraction:
* when a muscle contracts, the
thick myosin filaments and the
thin actin filaments maintain
the same length as in the
resting muscle, but the thin
actin filaments slide more
deeply into the A-bands, thus
shortening the sarcomeres along
the entire length of the
myofibrils.

*
* This accounts for the change in breadth of the H-band in different phases
of the contractile cycle.
* Its width is defined as the distance between the ends of the actin
filaments extending into the sarcomere from the opposite ends.
* It is widest in resting muscle and becomes narrower in contracted
muscle, due to the depper penetration of the actin filaments into the A-
band.
* Sliding of filaments is initiated by an influx of calcium ions into the
muscle fibers.
* Calcim storage and release to the myofibrils is the function of the
sarcoplasmic reticulum, a specialization of endoplasmic reticulum unique to
muscle.
* Most of the oganelles of muscle fibers do not differ significantly
from those of other cells and need not be described again. The
only exception is the sarcoplasmic reticulum, which corrsponds
to the endoplasmic reticulum of other cells but has acquired
physiological properties not typical of that organelle. It is the
site of sequestration of calcium during muscle relaxation and
release of calcium into the sarcoplasm to trigger muscle
contraction

*
* It consists of a network of membrane-bounded tubulues
surrounding each myofibril, and it exhibits a repeating pattern
related to specific regions of the sarcomeres.
* The tubules are largely devoid of associated polyribosome.
* Their prevailing orientation is longitudinal, but there are lateral
branches that form a closed-meshed network around the muyofibril at
the level of the H-band of each sarcomere.
* Over each junction of an A-band with an I-band, the longitudinal
sarcotubules are confluent with a pair of parallel transverse
tubules of larger caliber, called the terminal cisternae.
* Thus, along the myofibrils, two pairs of parallel terminal cistermae
are associated with each sarcomere.
* Between each pair of terminal cistermae there is slender transvere
tubule, commonly called the T-tubule, which is not an integral
part of the sarcoplasmic reiticulum but is a tubular invagination of
the sarcolemma that extends inward from the surface of the fiber,
crossing many myofibrils.
* Its membrane is continuous with the sarcolemma, where its lumen is
open to the extracellular space.
* The two parallel terminal cisternae and the intervening T-tubule form a
complex reffered to as the triad.
* To distinguish the terminal cisternae from the longitudinal elements of the
reticulum, they are often referred to as the junctional reticulum.

* The lumen of the terminal cistermae contains an amorphous material of low

density consisting mainly of calsequestrin, a 55-kDa protein that can bind 300
nM of calcium per miligram and is believed to serve as a sequestering agent for
the storage of calcium within the junctional retriculum.

* In that portion of the membrane of the terminal cisternae that adjoints the T-
tubule there are clusters of intramembranous particles, each surrounding a
calcium channel in the membrane. These particles are believed to contain Ca2+-
Mg2+-ATPase that is resposible to transport of Ca2+ from the sarcoplasm back
into the lumen of the transvere tubules during the relaxation phase of the
contractile cycle.
* Stimulation of muscle begins at the myoneural juction with the
generation of an action potential that spreads over the
sacrolemma and along the membrane of the T-tubules to the
interior of the muscle fibers.
* This initiates events at the interface between the T-tubules and
the terminal cisternae that result in the rapid release of the
sequestered calcium ions into the sarcoplasm, in resting muscle,
the bionding sites for myosin on the thin filaments are blocked
by the tropomyosin-troponin complexes.
* Release of calcium into the sarcoplasm is followed by its binding
to troponin C of each unit along the actin filaments. This results
in a conformational change in the complex that drives it depper
into the groove of the actin helix, exposing the myosin-binding
sites.

*
* Binding to heads of the myosin molecules of the adjacent thick
filaments then activates myosin ATPase. This, in turn, releases
energy that induces felxion of the heads of the myosin
molecules with a force sufficient to slide the neighboring actin
filaments a short distance toward the middle of the A-band.
* The myosin heads then detach and reattach to the next set of
binding sites of the actin filament for a new cycle of bridge
making and bridge breaking.
* Hundreds of such cycles take place to produce the observed
displacement of the actin filaments.
* This continues until calcium is taken up and sequestered in the
terminal cisternae of the sarcoplasmic reticululum and the
tropomyosin-troponin complexes again cover the myosin-
binding sites on the actin filaments, restoring the resting state
of the muscle.
* Skeletal muscles are innervated by axons of nerve cells located
in the spinal cord.
* At the muscle, the nerve divides into multiple branches that
penetrate into its interior via the perimyseal septa.
* Individual axons then ramify in the endomyseum and form
endings on a variable number of the muscle fiber.

*
* A single motor neuron may innervate from 1 to over 100 muscle
fibers.
* The axon and the muscle fibers it innervates constitue a motor
unit.
* The acitivation of a single axon will result in a muscle tension
proportional to the number of muscle fibers innervated by that
axon.
* In the graded response which is possible in whole muslces, the
strength of contraction depends on the number of motor units
that are activated.
* At its junction with a muscle fiber, an axon loses its myelin
sheath and branches into several short axon terminals (terminal
boutons) that occupy shallow depressions in the surface of the
fiber.
* Together, these structures constitute a motor end-plate or
myoneural junction.
* The sarcolemma beneath the end-plate is infolded to form a number of
synaptic clefts that serve to increase the area of sarcolemma exposed to
neutrotransmitter.
* The axoplasm of the nerve terminal contains a few mitichondria and a
large number 40-60nm synaptic vesicles that contain the
neurotransmitter acetylcholine.
* In impulse transmisson, the content of theses vesicles is released into
the space between the axon terminals and the muscle fiber.

* Acetylcholine diffusing across the cleft reaches acetylchoile receptrors in

the sarcolemma.
 * is an autoimmune disease characterized by muscular weakness
and fatigability.
* For unkown reasons, antibodies are formed against
acetylcholine receptors in the postsynaptic membrane of the
muslce fibers.
* Failure of transmission of the nerve impulse at many
neuromuscular junctions results in weak contractions

*
* red fibers
* white fibers
* intermediate fibers.

*
*
* The red fibers (slow twitch fibers) are smaller in diameter
and have a dark color.
* The deeper color is attributable to their greater content of
myoglobin and to the cytochromes in their unusually large and
abundant mitochondira.
* Lipid droplets are common in their sarcoplasm and the Z-
bands are wider than in the other fiber types.
* They are innervated by slender axons with relatively
simple motor end-plates.
* Motor units consisting of red fibers contract relatively
slowly but are more resistant to fatigue than other types
because of their greater ability to regenerate ATP.
* These properties make muscles that are rich in red fibers
well suited for postural maintenance.
*
* White fibers (fast twitch fibers) are the largest of the fiber types.
* Their subsarcolemmal mitochondria are smaller than those of red
fibers, and motochondria between the myofibrils are relatively few.
* Their generation of ATP depends on anaerobic glycolysis of glucose
derived from glycogen in their sarcoplasm.
* They are innervated by large axons that have motor end-plaes about
twice the size of those of red fibers.
* They contract rapidly and generate a large force, but they fatigue
rapidly.
* They are best suited for brief bursts of intense muscle activity.
* As their name implies, the intermediate fibers have charateristics
intermediate between the red and white fibers.
* The disposition of their mitochondria is similar to that of red fibers,
except that thick interfibrillar columns of mitochondira are seldom
found.
 * Unlike skeletal muscle, cardiac muscle consists of seperate
cellular units, cardiac myocytes, which are about 80 um in
length, 15 um in diameter, and are joined end-to-end at
junctional specialization called intercalated disks.

*
* Cardiac myocytes have an oviod, centrally
placed nucleus surrounded by myofibrils having
a pattern of cross-striations similar to that of
skeletal muscle.

* These diverge around the nucleus, outlining a

fusiform central region of sarcoplasm rich in
organelles and inclusions.
* A small Golgi complex is found near one pole of
the nucleus.
* Lipid droplets are common in this region and,
in elderly individuals, granular deposits of
lipochrome pigment may be abundant,
constituting up to 20% of the dry weight of the
myocardium.
* The principal identifying features of cardiac myocytes are the
centrally placed single nucleus and the occurrence of
transverse intercalated disks, at intervals along the length of
the myofibers.
* These are specialized junctions between cardiac myocytes.

* An intercalated disk may extend straight across the fiber,

but, more commonly segments of it are slightly offset
longitudinally, giving it a staircaselike configuration. The
dense transverse portions of the disk are sites of attachment
of the myofilaments to the sarcolemma.

*
* The intercalated disk is comparable to the zonula adherens of
epithelial junctons. Its dense material includes the actin-
binding, proteins a-actinin and vinculin.
* A distinctive feature of cardiac muscle in cross
section is the absence of distinct, polygonal
myofibrils of uniform size.

* The bulk of the cross section is occupied by a

continuum of myofilaments, interrupted here
and there by rows of circular profiles of
tubules of the sarcoplasmic reticulum and by
mitochondira
* The slender T-tubules of skeletal muscle are located at the level of A-I junctions. In cardiac muscle,
they are of larger caliber and occur at the level of the Z-disks.

* They are not flanked by long terminal cisternae. Therefore, triads are lacking.
* The tubules of the sarcoplasmic reticulum are less numerous than those of skeletal muscle.
* They form a subsarcolemmal network of tubules 25-35 nm in diameter, called the corbular reticulum,
that continues into deep celfts within the column of myofilaments.
* The reticulum is close-meshed adjacent to A-bands and more loosely organized at I-bands.
* The functional counterparts of the terminal cisternae are relatively small saccular dilatations of
certain longitudinal tubules of the reticulum that establish close contact with the T-tubules at the
level of the Z-disks. These complexes are called dyads.

* Transduction of excitation takes place in these structures via rows of transmembrane particles called
feet, or spanning proteins, bridging the gap between the T-tubule and the junctional saccule of the
reticulum.
* In addition, there are small expansions of the of the subsarcolemmal reticulum that are connected
directly to the sarcolemma by junctional feet.
* The calcium-binding protein calsequestrin can be localized in the junctional saccules and
neighbroing tubules of the reticulum.
* Owing to its less extensive juctional reticulum, cardiac muscle has limited intracellular reserves of
calcium. During depolarization of the sarcolemma and of the membrane of the T-tubules, an influx
of extracellular calcium is thought to supplement the intracellalular reserves in the reticulum.
filament sliding is evidently activated by calcium from both sources.
* There are differences in size of the myocytes in different regions of the heart. Those of the atria
tend to be smaller than those of the ventricles, and transverse tubules are shorter. Indeed, they are
seen only in the largest atrial fibers. It is likely that there is less need for transverse tubules for
inward conduction of excitation in fibers of small diameter.
* There are specialized myocytes in the right and left atrial
appendages that secrete peptide hormones.
* These are involved in the regulation of blood volume and the
electrolyte composition of the extracellular fluid.
* The myoendocrine cells resemble working myocytes in having
myofilaments that diverge around a central nucleus.

*
* The oraganelles do not differ significantly from
those of myocytes elsewhere.
* Their most distinctive feature is the presence of
many membrane-bounded secretory granules, 0.3
– 0.4 um in diamter in the core sarcoplasm that
extends in either direction from the poles of the
nucleus.

* The granules contain the precursor of a family of

peptides, collectively called cardiodilatins or
artial natriuretic peptide.
* These peptides are released into the blood and
cause peripheral vasodilatation and consequent
lowering of blood pressure.
* They also constrict the efferent arteriole of the
renal glomeruli resulting in diuresis (increased
urine) and increased excretion of sodium.
 * For the heart to function as an efficient pump,
contraction of the atria must be completed
shortly before the onset of ventricular
contraction. The precise timing of these events
of the cardiac cycle depends on myocytes that
are specialized for initiation and conduction of
excitation to the different regions of the
myocardium at a rate that will ensure their
activation in te correct sequence.

*
* The sinoatrial node, at the junction of the superior vena cava
with the right atrium, is considered the pacemaker of the
heart.
* It consists of pale-staining, highly branched nodal myocytes
containing relatively few myofilaments, and these are inconsisitent
in their orientation.
* The node is richly vascularized, contains considerable connective
tissue, and is innervated by both divisions of the autonomic nervous
systems.
* The nodal mycotes have an inherent rhythm of depolarization and
repolarization that is faster than that of the working myocardium.
* Their sointaneous depolarization initiates waves of excition that
spread, via gap junctions, though the atria and ventricles,
deternining their rate of contaction.

* However, the inherent rhythm of the node can be modified by

input from the autonomic nervous system.

* Syempathetic nerve impulses accelrate the heat rate and

parasympathetic nerve impulses slow the heart beat.