Download Muscle Tissue

Muscle Tissue
Muscles can be divided into three main groups according to their structure:
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Smooth muscle tissue.
Skeletal muscle tissue.
Cardiac (heart) muscle tissue.
Characteristics of muscle:
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excitability - responds to stimuli (e.g., nervous impulses)
contractility - able to shorten in length
extensibility - stretches when pulled
elasticity - tends to return to original shape & length after contraction or extension
Functions of muscle:
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motion
maintenance of posture
heat production
Skeletal muscle is attached to the skeleton and moves the body and its components. It appears striated (striped)
under the microscope and is under voluntary control. The biceps of the arm is an example of skeletal muscle.
Cardiac muscle is only located in the heart. Cardiac muscle is also striated, but is not normally under voluntary
control. Smooth muscle surrounds blood vessels and other passageways and alters the size of openings or
passageways and propels material through body tubes. Smooth muscle is distributed throughout the body. It
lacks striations and is involuntary. The respiratory and digestive tracts have layers of smooth muscle in their
walls.
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Skeletal Muscle Ultrastructure
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A skeletal muscle fiber is formed from the fusion of many embryonic cells during development to form
slender cells that extend from one end of the muscle to the other. Each muscle fiber normally has one
nerve fiber that extends to the cell membrane, forming the neuromuscular junction. There is a 100nanometer space, the synaptic cleft, between the nerve fiber and the muscle fiber.
The muscle cell membrane forms inward projections, the transverse tubules, associated with the cell's
smooth endoplasmic reticulum (sarcoplasmic reticulum). The sarcoplasmic reticulum stores calcium
and surrounds bundles of contractile proteins. The contractile proteins, which do the work of
contraction, are parallel and arranged in an overlapping pattern that gives rise to the muscle striations.
The pattern of striations is repeated many times down the length of the muscle fiber in segments called
sarcomeres.
The proteins of the sarcomere are grouped in thick filaments and thin filaments. Contraction occurs
when thick and thin filaments slide past each other, pulling the muscle ends closer together. A thick
filament is a bundle of approximately two hundred myosin proteins. A portion of each myosin protein
projects outward to form myosin heads.
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Thin filaments overlap the thick filaments and are composed of three types of protein molecules. The
main protein is actin. Three hundred to four hundred molecules of globular actin (G actin) link like
beads in a necklace to form a strand called fibrous actin (F actin). Two such "necklaces" are then
intertwined into a loose double helix. In the groove between the two F-actins, much like a string, is the
protein tropomoysin. Each G- actin contains an active site to bind the myosin head. When the muscle is
at rest, tropomyosin covers the active sites of actin. Attached to tropomyosin is troponin, a small
complex of three polypeptides. This structural arrangement allows muscle to contract.
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Muscle Contraction
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Muscle contraction begins when the nerve fiber releases the neurotransmitter acetylcholine into the
synaptic cleft. Acetylcholine moves across the synaptic cleft and binds to receptors on the muscle fiber.
This indirectly initiates an action potential , a change of electrical charge at the membrane that is
similar to events in a neuron. The action potential spreads across and into the muscle fiber via the
transverse tubules and triggers the release of calcium from the sarcoplasmic reticulum. Next, calcium
binds to troponin, causing the troponin to change shape. Since troponin is attached to tropomysin, as
troponin changes shape the tropomysin is pulled away from the active sites of actin, which become
exposed. The myosin head, which was previously blocked by tropomysin, now binds to the active site of
actin, forming a cross-bridge between the thick and thin filament.
Myosin pulls the thin filament past the myosin as the myosin head repeatedly flexes, lets go of the actin,
extends and attaches to a new active site, and flexes again. As the many myosin heads continue to repeat
this process, thin filaments slide past the thick filaments and the sarcomere is shortened. Shortening of
all sarcomeres within the muscle fiber results in contraction of the whole fiber.
Muscle relaxes and returns to its original form when tropomyosin covers up the active sites of
actin, preventing the formation of cross-bridges. Relaxation also involves the destruction of
acetylcholine by acetylcholinesterase in the synaptic cleft, ending muscle stimulation, and the reuptake of calcium into the sarcoplasmic reticulum. Without calcium, troponin returns to its
original shape, pulling tropomyosin back over the active sites of actin. Myosin no longer forms
cross-bridges, so the muscle relaxes.
Depolarization of the T-tubule membrane causes a release of calcium ions from the sarcoplasmic
reticulum, triggering muscle contraction.
Myosin heads in a myosin thick filament cluster to the outside, with the tails lining up inside. The
heads on either end point in opposite directions. During muscle contraction, the heads pull actin
filaments together toward the center bare zone, contracting the muscle fiber.
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Energy (ATP) Requirements
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The contraction of muscle fibers requires a large amount of energy in the form of adenosine triphosphate
(ATP). ATP is made available through various mechanisms. A limited amount of ATP is stored in the
muscle cell. ATP is also produced by a phosphate transfer from creatine phosphate to ADP; muscles do
store larger amounts of creatine phosphate. The stored ATP and the ATP created from creatine
phosphate are available for immediate use and provide approximately enough ATP for about six seconds
of exercise.
Additional ATP can be produced through anaerobic and aerobic metabolism. Aerobic respiration
provides a larger production of ATP but depends on sufficient oxygen delivery. Myoglobin, a protein in
muscle cells that binds oxygen, contributes some of the oxygen for aerobic respiration. Aerobic ATP
production also requires mitochondria . Muscles packed with mitochondria give meat a darker color
("dark meat") than muscles with fewer mitochondria ("white meat"). Anaerobic fermentation provides
less energy but can produce ATP in the absence of oxygen. A serious drawback of anaerobic
fermentation is the production of lactic acid, a product that can alter cell pH . Both processes can use
glucose released from glycogen, which is stored in muscles as a reserve fuel.
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Muscle Fatigue
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A decrease in the ability of muscle to contract is muscle fatigue. Muscle fatigue can result from short
burst of maximum effort, such as a 50-meter swim, or sustained long-term activities such as marathon
running. The cause of fatigue depends on the activity. Fatigue from short, extensive burst of activity can
result from depletion of ATP or buildup of lactic acid. Muscle fatigue from sustained activities can
result from depletion of fuel molecules or depletion of acetylcholine at the neuromuscular junction.
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Hypertrophy and Conditioning
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Through training, a muscle can become larger (hypertrophy) and have greater endurance. A muscle
grows mainly by increasing the number of thin and thick filaments within the fibers. Growth results
from repeated contractions of muscle, as in weight lifting. Muscle conditioning is the increased ability of
the muscle to perform a task, either because of greater strength or better fatigue-resistance. Many
changes in muscle performance, however, result from changes in the cardiovascular and respiratory
systems, enabling them to deliver fuel and oxygen to muscle fibers more efficiently. Many changes
specific to muscle fibers involve enhancing energy production, including an increase in number of
mitochondria and myoglobin and greater storage of glycogen.
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Diseases affecting muscle can result from loss of neurons that stimulate the muscle, such as polio;
changes in the neuromuscular junction that result in loss of ability to stimulate the muscle, such as
myasthenia gravis (an autoimmune disease); or loss of structural integrity of the muscle fiber, such as
muscular dystrophy. All result in decreased ability of the muscle to contract and sometimes the complete
loss of the muscle's function.
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SMOOTH MUSCLE
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Smooth muscle is responsible for the contractility of hollow organs, such as blood vessels, the
gastrointestinal tract, the bladder, or the uterus. Its structure differs greatly from that of skeletal
muscle, although it can develop isometric force per cross-sectional area that is equal to that of
skeletal muscle. However, the speed of smooth muscle contraction is only a small fraction of that
of skeletal muscle.
Structure: The most striking feature of smooth muscle is the lack of visible cross striations (hence
the name smooth). Smooth muscle fibers are much smaller (2-10 m in diameter) than skeletal
muscle fibers (10-100 m ). It is customary to classify smooth muscle as single-unit and multi-unit
smooth muscle (Fig. SM1). The fibers are assembled in different ways. The muscle fibers making
up the single-unit muscle are gathered into dense sheets or bands. Though the fibers run roughly
parallel, they are densely and irregularly packed together, most often so that the narrower portion
of one fiber lies against the wider portion of its neighbor. These fibers have connections, the
plasma membranes of two neighboring fibers form gap junctions that act as low resistance
pathway for the rapid spread of electrical signals throughout the tissue. The multi-unit smooth
muscle fibers have no interconnecting bridges. They are mingled with connective tissue fibers.
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Electron micrographs of smooth muscle reveal that the actin filaments are organized through
attachment to the dense bodies that contain a-actinin, a Z-band protein in skeletal muscle. Thus, it
is assumed that the dense bodies function as Z-lines. The ratio of thin to thick filaments is much
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higher in smooth muscle (~15:1) than in skeletal muscle (~6:1). Smooth muscle is rich in
intermediate filaments that contain two specific proteins, desmin and vimentin.
Innervation and stimulation: Smooth muscle is primarily under the control of autonomic nervous
system, whereas skeletal muscle is under the control of the somatic nervous system. The singleunit smooth muscle has pacemaker regions where contractions are spontaneously and
rhythmically generated. The fibers contract in unison, that is the single unit of smooth muscle is
syncytial. The fibers of multi-unit smooth muscle are innervated by sympathetic and
parasympathetic nerve fibers and respond independently from each other upon nerve stimulation.
Nerve stimulation in smooth muscle causes membrane depolarization, like in skeletal muscle.
Excitation, the electrochemical event occurring at the membrane is followed by the mechanical
event, contraction. In the case of smooth muscle, this excitation-contraction coupling is termed
electromechanical coupling; the link for the coupling is Ca2+ that permeates from the extracellular
space into the intracellular water of smooth muscle. There is another excitation mechanism in
smooth muscle, which is independent of the membrane potential change; it is based on receptor
activation by drugs or hormones followed by muscle contraction. This is termed
pharmacomechanical coupling. The link is Ca2+ that is released from an internal source, the
sarcoplasmic reticulum.
The role of mechanical events of smooth muscle in the wall of hollow organs is twofold: 1) Its tonic
contraction maintains organ dimensions against imposed load. 2) Force development and muscle
shortening, like in skeletal muscle.
The heart is the pump that keeps blood circulating throughout the body and thereby transports nutrients,
breakdown products, antibodies, hormones, and gases to and from the tissues. The heart consists mostly of
muscle; the myocardial cells (collectively termed the myocardium) are arranged in ways that set it apart from
other types of muscle. The outstanding characteristics of the action of the heart are its contractility, which is the
basis for its pumping action, and the rhythmicity of the contraction.
Heart muscle differs from its counterpart, skeletal muscle, in that it exhibits rhythmic contractions. The amount
of blood pumped by the heart per minute (the cardiac output) varies to meet the metabolic needs of the
peripheral tissues (muscle, kidney, brain, skin, liver, heart, and gastrointestinal tract). The cardiac output is
determined by the contractile force developed by the heart cells (myocytes), as well as by the frequency at
which they are activated (rhythmicity). The factors affecting the frequency and force of heart muscle
contraction are critical in determining the normal pumping performance of the heart and its response to changes
in demand.
Structure and organization
The heart is a network of highly branched cardiac cells 110 μm in length and 15 μm in width, which are
connected end to end by intercalated discs. The cells are organized into layers of myocardial tissue that are
wrapped around the chambers of the heart. The contraction of the individual heart cells produces force and
shortening in these bands of muscle, with a resultant decrease in the heart chamber size and the consequent
ejection of the blood into the pulmonary and systemic vessels. Important components of each heart cell
involved in excitation and metabolic recovery processes are the plasma membrane and transverse tubules in
registration with the Z lines, the longitudinal sarcoplasmic reticulum and terminal cisternae, and the
mitochondria. The thick (myosin) and thin (actin, troponin, and tropomyosin) protein filaments are arranged
into contractile units (that is, the sarcomere extending from
Z line to Z line) that have a characteristic cross-striated pattern similar to that seen in skeletal muscle.
The frequency of contraction
The rate at which the heart contracts and the synchronization of atrial and ventricular contraction required for
the efficient pumping of blood depend on the electrical properties of the myocardial cells and on the conduction
of electrical information from one region of the heart to another. Each of the phases of the action potential is
caused by time-dependent changes in the permeability of the plasma membrane to (K+), (Na+), and (Ca2+). The
resting potential of the myocytes of the ventricle (phase 4) begins with the outside of the cell being positive—
i.e., having a greater concentration of positive ions. Atrial and ventricular myocytes are normally quiescent
(nonrhythmic); however, when the resting membrane potential is depolarized to a critical potential (Ecrit), a selfgenerating action potential follows, leading to muscle contraction. Phase 0, the upstroke, is associated with a
sudden increase in membrane permeability to Na+. Phases 1, 2, and 3 result from changes in membrane
permeability and conductance to Na+, K+, and Ca2+.
The electrical activity of heart muscle cells differs substantially from that of skeletal muscle cells in that phases
1, 2, and 3 are considerably prolonged (200 milliseconds versus 5 milliseconds, respectively). Another
significant difference in excitability is that heart muscle cannot be tetanized (i.e., induced to spasm) by the
application of repetitive stimuli (see above striated muscle), thus ensuring the completion of the
contraction/relaxation cycle and the effective pumping of blood.
Because atrial and ventricular cells are normally quiescent, exhibiting action potentials only after the muscle is
depolarized to the critical membrane potential (Ecrit), the source of the rhythmic contractions of the heart must
be sought elsewhere. In contrast to atrial and ventricular myocytes, the myocytes of the sinoatrial (SA) node, the
atrioventricular (AV) node, the bundle branches, and the Purkinje Fiber system are made up of specialized
cardiac muscle cells that exhibit a spontaneous upward drift in the resting potential toward Ecrit, resulting in the
generation of the action potential with all of its phases. The normal rhythmicity of cells from each of these
regions depends on the rate at which spontaneous depolarization occurs and the resting membrane potential
from which it starts. The region with the fastest intrinsic rate, the SA node, sets the pace for the whole heart.
The pacemaker activity is propagated to the rest of the heart by means of the low electrical resistance pathways
through the muscle cells (e.g., intercalated disks) and the presence of specialized conducting tissue (e.g., bundle
branches and the Purkinje system). The time course of activation and the shape of the action potentials in
different parts of the heart are responsible for the synchronous activation and contraction of the muscles of the
atrium followed by those of the ventricle.
The normal rhythm of the heart (i.e., the heart rate) can be altered by neural activity. The heart is innervated by
sympathetic and parasympathetic nerves, which have a profound effect on the resting potential and the rate of
diastolic depolarization in the SA nodal region. The activity of the sympathetic nervous system may be
increased by the activation of the sympathetic nerves innervating the heart or by the secretion of epinephrine
and norepinephrine from the adrenal gland. This decreases the resting potential of the myocytes of the SA node
while increasing the rate of diastolic depolarization. The result is an increase in the heart rate. Conversely,
stimulating the parasympathetic nervous system (vagal nerves to the heart) increases the resting potential and
decreases the rate of diastolic depolarization; under these circumstances the heart rate slows. The sympathetic
nervous system is activated under conditions of fright or vigorous activity (the so-called fight-or-flight
reaction), where the increase in force and rate of heart contraction are easily felt; the parasympathetic system
exerts its influence during periods of rest.
Excitation/contraction coupling
Immediately following depolarization of the plasma membrane and the ensuing action potential, the heart
muscle develops force and then relaxes. The surface action potential is transmitted to the interior of the muscle
by means of the transverse tubular system. Calcium ions enter the muscle cell during the plateau phase action
potential (phase 2), triggering the release of calcium from the terminal cisternae of the sarcoplasmic reticulum.
Calcium diffuses to the myofilaments and combines with the troponin-tropomyosin system (associated with the
thin actin filaments, producing a conformational change that allows actin and myosin to interact. This
interaction in the presence of ATP results in cross bridge cycling and ATP hydrolysis. The force developed in
the whole muscle is the sum of all the forces developed by each of the millions of cycling cross bridges of the
muscle. The free calcium ions in the cytosol are removed by an energy-dependent calcium uptake system
involving calcium ion pumps located in the longitudinal sarcoplasmic reticulum. These calcium pumps lower
the concentration of free calcium in the cytosol, resulting in the dissociation (release) of calcium from the
troponin-tropomyosin system. The troponin-tropomyosin system is then transformed back to its original state,
preventing myosin and actin from interacting and thus causing relaxation of the muscle. At the same time,
calcium is extruded from the cell into the surrounding medium.
Force and velocity of contraction
There are a number of factors that change the force developed by heart muscle cells. In a manner similar to that
seen in skeletal muscle, there is a relationship between the muscle length and the isometric force developed. As
the muscle length is increased, the active force developed reaches a maximum and then decreases. This
maximum point is the length at which the heart normally functions. As with skeletal muscle, changes in length
alter the active force by varying the degree of overlap of the thick myosin and thin actin filaments. The force
developed by heart muscle also depends on the frequency at which the muscle is stimulated. As the stimulus
frequency is increased, the force is increased until the maximum is reached, at which point it begins to decrease.
An increase in the level of circulating epinephrine and norepinephrine from the sympathetic nervous system
also increases the force of contraction. All these factors can combine to allow the heart to develop more force
when required. At any given length the velocity of contraction is a function of the load lifted, with the velocity
decreasing as the load is increased.
Response of the heart to stress
Demands on the heart vary from moment to moment and from day to day. In moving from rest to exercise, the
cardiac output may be increased tenfold. Other increases in demand are seen when the heart must pump blood
against a high pressure such as that seen in hypertensive heart disease. Each of these stresses requires special
adjustments. Short-term increases in demand on the heart (e.g., exercise) are met by increases in the force and
frequency of contraction. These changes are mediated by increases in sympathetic nervous system activity, an
increase in the frequency of contraction, and changes in muscle length. The response to long-term stress
(hypertension and thyrotoxicosis) results in an increase in the mass of the heart (hypertrophy), providing more
heart muscle to pump the blood, which helps meet the increase in demand. In addition, subtle intracellular
changes affect the performance of the muscle cells.
In the pressure-overload type of hypertrophy (hypertensive heart disease), the pumping system of the
sarcoplasmic reticulum responsible for calcium removal is slowed while the contractile protein myosin shifts
toward slower cross-bridge cycling. The outcome is a slower, more economical heart that can meet the demand
for pumping against an increase in pressure. At the molecular level the slowing of calcium uptake is caused by a
reduction in the number of calcium pumps in the sarcoplasmic reticulum. The change in the maximum velocity
of shortening and economy of force development occur because each myosin cross-bridge head cycles more
slowly and remains in the attached force-producing state for a longer period of time.
In the thyrotoxic type of hypertrophy, calcium is removed more quickly while there is a shift in myosin. At the
molecular level there are more sarcoplasmic reticular calcium pumps, while the myosin cross-bridge head
cycles more rapidly and remains attached in the force-producing state for a shorter period of time. The result is
a heart that contracts much faster but less economically than normal and can meet the peripheral need for large
volumes of blood at normal pressures.