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LECTURE 3. Physiology of Muscles

There are three types of muscle tissue: skeletal, cardiac, and smooth. These types differ in
structure, location, function, and means of activation.

The Skeletal Muscle Tissue is packaged in skeletal muscles that attach to and cover the bony
skeleton. This type of tissue has visible stripes called striations. It is controlled voluntarily (i.e.,
by conscious control). It contracts rapidly but is easily tired. It is responsible for overall body
motility. It is extremely adaptable and can exert forces over a broad range.

The Smooth Muscle Tissue is located in the walls of hollow visceral organs, such as stomach,
urinary bladder, and respiratory passages. It forces food and other substances through internal body
channels. It is not striated and is involuntary.

The Cardiac Muscle Tissue is present only in the heart. It is striated like skeletal muscle but is
not voluntary. It contracts at a fairly steady rate set by the heart’s pacemaker. Neural controls allow
the heart to respond to changes in bodily needs.

1. Functional Anatomy of Skeletal Muscle.

Skeletal muscles generally are connected to the bones of the skeleton by tendons. The part of
the muscle generating the force is called the body. The body contains bundles (fascicles) of muscle
cells. Muscle cells are called muscle fibers and are multinucleate. The plasma membrane is called
the sarcolemma.
The contractile component of muscle cells is contained within rod-like elements called
myofibrils. Myofibrils have overlapping thick and thin filaments myosin and actin, respectively.
The smooth endoplasmic reticulum surrounding the myofibrils is called sarcoplasmic reticulum
which is closely associated with inward extensions of the sarcolemma called transverse tubules.
Skeletal muscle is striated muscle due to the orderly arrangement of thick and thin filaments
that run parallel to the long axis of the fiber. Myofibrils are also composed of repeating units called
sarcomeres. Each sarcomere is bordered by Z disks that anchor the thin filaments. M lines are in
the center of the sarcomeres.
The sarcomere is banded with the following:
A band - appears dArk and is the length of the thick filaments
H zone - light region in the center of the A band
I band - lIght band where only thin filaments are located

Actin (thin) and myosin (thick) filaments are attached by cross bridges. Thin filaments are
composed of globular actin linked to form helical strands. Two regulatory proteins are associated
with actin. Tropomyosin extends over and covers binding sites on actin subunits. Troponin, a
complex of three proteins, uncovers binding sites when bound to calcium.
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Each myosin molecule is composed of two parts (dimer), with each part consisting of a tail
twisted around the other and a head. A thick filament consists of pairs of myosin molecules
with each pair attached by the ends of their tails. These pairs of myosin molecules are bundled
together so that their heads protrude in a helical pattern at either end with a bare zone in the
center. The head of the myosin molecule has a site that binds to actin to form crossbridges, and
an ATPase site that hydrolyzes ATP. Extending along the length of each thick filament from
the M line to each Z line is an elastic protein called titin. Titin gives the sarcomere elasticity so
that after it is stretched, it returns to its original position when it is relaxed. Titin also anchors
the thick filaments in the proper position.
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2. Mechanism of muscle contraction. Sliding-filament model.
This model explains muscle contraction by the sliding of thick and thin filaments over one
another. This model best explains the changes that occur in the bands and the zones when a muscle
contracts.
I band
Myosin
Z A band Z
Actin
Muscle
relaxed

Z
Z M Z A band line
Half of H zone Half of
I band I band

Sarcomere shortens
with contraction H Half of M Z
Z A band constant Z I band line line
Muscle
contracted

I H I
H zone and I band both shorten

Sequence of main events during muscular contraction:

1. Spread of action potential along the muscle fiber
2. Depolarization of the transverse tubule system
3. Transverse tubule depolarization causes Ca++channels in the lateral sacs of the sarcoplasmic
reticulum (SR) to open; the increase in Ca-permeability leads to rapid passive diffusion from the
SR into the fiber cytoplasm
4. Some of the Ca++ions bind to troponin, permitting the formation of actin-myosin cross
bridges
5. Using the energy provided by ATP →ADP conversion at the bridge site, the cross bridge
reorients, leading to muscle contraction
6. A new ATP replaces the ADP at the bridge site, permitting the bridge to break
7. A new bridge is formed at the next site, etc., leading to continued contraction
8. When the fiber repolarizes, the Ca++ channels close and the cytoplasmic Ca++ is
resequestered into the lateral sacs
9. Cross bridges cease forming and muscle relaxes

3.Role of ATP in Producing Muscle Contraction

Most of the muscle contraction proceeds without ATP. The attachment of myosin to actin
is not ATP dependent; neither is the resulting change in confirmation in the myosin molecule. It is
believed that this change in shape of the myosin molecule exposes an ATP binding site. The
binding of ATP to this site causes the myosin to be released from the actin. The ATP molecule then
degrades to ADP, and the energy released causes the myosin molecule to return to its original
confirmation. The myosin is then ready to bind to the next actin binding site.
If ATP were to be depleted, as occurs following death, then the actin and myosin
molecules would not separate, and would be permanently fixed together. This would cause the
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muscle length to become fixed, and the muscle would appear to be very stiff. In fact, this
phenomenon explains “rigor mortis”. ATP deficiency may cause muscle contractures at high
loads (for example in sport). Moreover, ATP is needed for active transport Ca++ into the
sarcoplasmic reticulum.
When the muscle is stimulated to contract, the supply of ATP in the muscle may become rapidly
depleted under high exertion. The muscle cell gears up its ATP production to meet the demand but
for a few seconds energy is supplied by the creatine/creatine phosphate system. Creatine
phosphate in the resting cell can produce ATP by the reaction
creatine phosphate+ADP<=>creatine +ATP
The reaction is catalyzed by creatine kinase. There is enough creatine phosphate in the cell to
supply four to five times the quantity of preformed ATP.
The ability to produce ATP is limited. Creatine phosphate stores are exhausted within 20
seconds of the onset of maximal exercise, and anaerobic glycolysis is limited by decreased glucose
levels and a buildup of lactic acid. Aerobic respiration can produce ATP for long periods, but is
limited by oxygen and nutrient delivery by the blood. When the need for ATP is exceeded by the
ability to produce ATP through anaerobic glycolysis and aerobic respiration, contractions decrease
in strength or exercise slows or stops.
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4. Motor units and their characteristics.

A whole skeletal muscle consists of motor units. A motor unit consists of a single motor
neuron and all of the muscle cells stimulated by it. Quantity of the muscle cells per motor neuron
varies from 4 to 400. There are fewer muscle cells per neuron in the muscles of fine control (fingers,
eyes and face) and more muscle cells per neuron in the muscles, responsible for posture and gross
movement (gluteus maximus). Axon terminals are distributed on muscle fibers throughout the
muscle (not one region). Stimulation of one motor unit causes weak contraction throughout the
whole muscle. If more than one motor unit is stimulated, the strength of muscle contractions
increases.
The contraction velocity of the single motor unit depends on ratio of the different types of
muscle fibers, of which it is composed. There are three major types of skeletal muscle fibers: slow-
twitch oxidative (SO or I type) fibers, fast-twitch glycolytic (FG or IIα type) fibers, and fast-twitch
oxidative glycolytic (FOG or IIβ type) fibers.
Red Slow-Twitch Fibers contain a lot of myoglobin (red) to store oxygen, many
mitochondria, active enzymes. They use fat as the primary fuel source, can produce ATP by aerobic
respiration and sustain a long duration contraction. Slow-twitch oxidative fibers are the most
fatigue-resistant because they can produce a lot of ATP to support muscle contraction.
White Fast-Twitch Fibers are fast twitch. They contain few mitochondria. Their metabolism
is primarily anaerobic. They store glycogen used for anaerobic respiration. These fibers produce the
lactic acid and fatigue quickly. Their contractions are rapid, intense, but short-term. Fast-twitch
glycolytic fibers are the most fatigable fibers because they produce little ATP.
Intermediate Fast-Twitch Fibers (medium, pink) are fast twitch; Their metabolism is aerobic
with myoglobin present. They are somewhat resistant to fatigue and produce strong rapid
contractions like white fast-twitch fibers.
Most muscles have combinations of all 3 types of fibers. But the ratio of each type of the
fibers is different among inividuals. Individual differences in muscle type ratios are mostly
genetically determined.
Humans exhibit no clear separation of slow-twitch and fast-witch muscle fibers in individual
muscles. Most muscles have both types of fibers, although the number of each type varies in a given
muscle. The large postural muscles contain more slow-twitch fibers, whereas muscles of the upper
limb contain more fast-twitch fibers. People who are good long-distance runners have a higher
percentage of slow-twitch fibers, whereas good sprinters have a greater percentage of fast-twitch
muscle fibers in their lower limbs. Athletes who are able to perform a variety of aerobic and
anaerobic exercises tend to have a more balanced mixture of slow-twitch and fast-twitch muscle
fibers.
The distribution of slow-twitch and fast-twitch muscle fibers in a given muscle is fairly
constant for each individual and apparently is established developmentally. SO fibers are not
converted to FG or FOG fibers, and vice versa. Aerobic exercise training, however, can convert FG
fibers to FOG fibers, resulting in increased endurance.
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5. The types of muscle contraction depending on the frequency of stimulation.

A single stimulus can (?) cause one or more fibers to contract and then to relax. Such a
contraction is called the muscle twitch.
The time between application of the stimulus to the motor neuron supplying the muscle fiber
andthebeginning of contraction is called the lag phase or latent phase; the time during which
contraction occurs is called the contraction phase; and the time during which relaxation occurs is
called the relaxation phase.
Events that occur during each phase of a muscle twitch are following:
Lag Phase
1. An action potential is propagated to the presynaptic terminal of the motor neuron, causing
voltage-gated Ca2+ channels in the presynaptic terminal to open.
2. Calcium ions diffuse into the presynaptic terminal, causing several synaptic vesicles to release
acetylcholine by exocytosis into the synaptic cleft.
3. Acetylcholine diffuses across the synaptic cleft and binds to acetylcholine receptor sites on
ligand-gated Na+ channels in the postsynaptic membrane of the sarcolemma, causing them to open.
4. Sodium ions diffuse into the muscle fiber, causing a local depolarization that exceeds threshold
and produces an action potential in the sarcolemma.
5. Acetylcholine is rapidly degraded in the synaptic cleft to acetic acid and choline by
acetylcholinesterase, thus limiting the length of time acetylcholine can stimulate the muscle fiber.
6. The action potential produced in the sarcolemma propagates into the T tubules, causing gated
Ca2+ channels of the membrane of the sarcoplasmic reticulum to open.
7. Calcium ions diffuse from the sarcoplasmic reticulum into the sarcoplasm and bind to troponin;
the troponin–tropomyosin complex changes its position and exposes active sites on the actin
myofilaments.
Contraction Phase
8. Cross-bridges between actin molecules and myosin molecules form, move, release, and re-form
many times, causing actin myofilaments to slide past myosin myofilaments; the sarcomeres shorten.
Relaxation Phase
9. Calcium ions are actively transported back into the sarcoplasmic reticulum.
10. The troponin–tropomyosin complexes move to inhibit cross-bridge formation.
11. The muscle fibers lengthen passively
When more then one stimulus acts on the muscle repeatedly, the frequency summation of
contractions occurs.

Frequency summation is the increased force of contraction of muscle fibers resulting from
increased frequency of stimulation. As stimulus frequency increases, there is not enough time for
muscle fibers to relax completely. Relaxation of muscle fibers, however, is not required before
action potentials can stimulate additional contractions. The force of additional contractions can be
added to the force generated by previous contractions, resulting in an overall increase in force of
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contraction (figure 8.14b). In incomplete tetanus , the frequency of action potential production
allows muscle fibers to only partially relax between contractions, producing a relatively steady
force of contraction (figure 8.14c). In complete tetanus, action potentials are produced so rapidly
that no relaxation occurs between contractions, resulting in a steady, maximal force of contraction
(figure 8.14d). Frequency summation can be explained by the effect of the action potentials on
Ca2+ release from the sarcoplasmic reticulum. The first action potential causes Ca2+ release from
the sarcoplasmic reticulum, the Ca2+ ions diffuse to the myofibrils, and contraction occurs.
Relaxation begins as the Ca2+ ions are pumped back into the sarcoplasmic reticulum. If the next
action potential occurs before relaxation is complete, two things happen. First, because not enough
time has passed for all the Ca2+ to reenter the sarcoplasmic reticulum, Ca2+ levels around the
myofibrils remain elevated. Second, the next action potential causes the release of additional Ca2+
from the sarcoplasmic reticulum. Thus, the elevated Ca2+ levels in the sarcoplasm produce
continued contraction of the muscle fiber.

6. The types of muscle contraction depending on the load. Muscle tone.

Depending on the load, all contraction are divided into two types: isotonic and isometric.
In isotonic contractions, the muscle changes in length (decreasing the angle of the joint) and
moves the load. The two types of isotonic contractions are concentric and eccentric:
Concentric contractions – the muscle shortens and does work.
Eccentric contractions – the muscle contracts as it lengthens.
During isometric contractions the tension increases up to the muscle’s capacity, but the muscle
neither shortens nor lengthens. It occurs if the load is greater than the tension the muscle is able to
develop.

Muscle tone is the constant tension produced by muscles of the body over long periods of
time. Muscle tone is responsible for keeping the back and legs straight, the head in an upright
position, and the abdomen from bulging. Muscle tone depends on a small percentage of the motor
units in a muscle being stimulated at any point in time and out of phase with one another. The
stimulation of the motor-units results in incomplete or complete tetanus, and not single muscle
twitches.
.
Factors that can affect the muscle contraction.
The force of contraction of a whole skeletal muscle is affected by:
• the number of muscle fibers contracting – the more motor fibers in a muscle, the stronger the
contraction. The number of fibers can be assessed by the cross section area of the muscle.
• the relative size of the muscle – the bulkier the muscle, the greater its strength
But this force can be regulated in a broad range depending on its load. The main factors
affecting the contraction force are:
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1. A recruitment of the motor units. A whole muscle contracts with either a small force
or a large force, depending on the number of motor units stimulated to contract by the nervous
system. Contraction of a few motor units results in a weak force, whereas contraction of many
motor units
produces a strong force. This effect is called multiple-fiber summation because, as more and more
(multiple) motor units (muscle fibers) are stimulated, the force of contraction increases (sums). It is
also called recruitment because the nervous system progressively enlists (recruits) the number of
motor units to increase the force of contraction. Motor units in different muscles do not always
contain the same number of muscle fibers. Muscles performing delicate and precise movements
have motor units with a small number of muscle fibers, whereas muscles performing more powerful
but less precise contractions have motor units with many muscle fibers. For example, in very
delicate muscles, such as those that move the eye, the number of muscle fibers per motor unit can
be less than 10, whereas in the large muscles of the thigh, the number can be several hundred.

2. Frequency of the stimulation. Frequency summation and multiple-fiber summation

work together to produce contractions of different force and smooth, steady movements. Normal
movements do not resemble individual muscle twitches. As a result of increased frequency of
stimulation by the nervous system, motor units exhibit incomplete or complete tetanus. As a result
of recruitment by the nervous system, the number of motor units contracting can gradually increase,
producing graded contractions. Muscles are capable of contracting either slowly or rapidly,
depending on the number of motor units stimulated and the rate at which that number increases or
decreases. Furthermore, asynchronous stimulation of motor units smooths out muscle contractions.
Instead of all the muscle fibers contracting at once, some are contracting while others are relaxing.
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Smooth, slow movements result from an increasing number of motor units contracting out of
phase as muscles shorten, as well as from a decreasing number of motor units contracting out of
phase as muscles lengthen.
3. Length of the muscle before contraction. The number of cross-bridges formed during
contraction determines the force of contraction. Just as many people pulling on a rope generates
more force than a few people pulling, the force of contraction of a muscle increases with the
number of cross-bridges formed. The number of cross-bridges that can form depends on the length
of the muscle when it is stimulated to contract. Muscle length determines sarcomere length, which
determines the amount of overlap between actin and myosin myofilaments. If a muscle is stretched
to its optimum length, optimal overlap of the actin and myosin myofilaments takes place. When the
muscle is stimulated, maximal cross-bridge formation results in maximal contraction (figure 8.16).
If a muscle is stretched so that the actin and myosin myofilaments within the sarcomeres do not
overlap or overlap to a very small extent, the muscle produces very little active tension when it is
stimulated because few cross-bridges form. Also, if the muscle is not stretched at all, the myosin
myofilaments touch each of the Z disks in each sarcomere, and very little contraction of the
sarcomeres can occur.

7. Fatigue and its mechanisms. Oxygen debt.

Fatigue is the decreased capacity to do work and the reduced efficiency of performance that
normally follows a period of activity. Psychologic fatigue involves the central nervous system and
is the most common type of fatigue. The muscles are capable of functioning, but the individual
“perceives” that additional muscular work is not possible. A determined burst of activity in a tired
athlete in response to pressure from a competitor is an example of how psychologic fatigue can be
overcome.
Muscular fatigue is a reduced or absent ability of muscle fibers to respond to stimuli.
Although many factors may be involved with muscular fatigue, the main problem appears to be
excitation-contraction uncoupling. When Ca2+ levels significantly increase in a contracting
muscle fiber, it somehow inhibits the ability of T-tubule voltage sensors to cause terminal cisternae
Ca2+ release channels to open. Thus, the muscle fiber becomes less sensitive to stimulation.
Moreover, a depletion of the transmitter in vesicles occurs, if a muscle is stimulated for a long time.
As a result of extreme muscular fatigue, muscles occasionally become incapable of either
contracting or relaxing—a condition called physiologic contracture . When ATP levels are very
low, active transport of Ca2+ into the sarcoplasmic reticulum slows and Ca2+ accumulate within
the sarcoplasm. The Ca2+ bind to troponin, which promotes the formation of cross-bridges and
contraction. With inadequate ATP, cross-bridge release does not occur, preventing relaxation.
There is a lag time between when exercise begins and when an individual begins to breathe
more heavily because of the exercise. After exercise stops, there is a lag time before breathing
returns to preexercise levels. Th e lag in oxygen consumption relative to increased activity at the
beginning of exercise creates an oxygen debt, which is repaid after exercise ceases. It was once
hypothesized that the “extra” oxygen consumed after exercise is used in aerobic respiration to
generate ATP that is used to reverse the effects of anaerobic processes. For example, the oxygen
debt restores creatine phosphate levels and removes lactic acid. It is now known that this
explanation is not complete. In recognition of the many known and unknown factors affecting
oxygen consumption following exercise, some authorities now use the term excess post-exercise
oxygen consumption (EPOC) instead of oxygen debt (or deficit). The duration of EPOC is
dependent on the individual’s physical conditioning and on the length and intensity of the exercise
session. It can last from a few minutes to many hours. Factors that initially contribute to EPOC
include synthesizing ATP and creatine phosphate and removing lactic acid (the oxygen debt
hypothesis). It also involves returning oxygen levels in the lungs, blood, and muscles to resting
levels and the effects of elevated body temperature, circulation, and ventilation. Factors responsible
for the prolonged part of EPOC are not completely understood, but fat metabolism plays a
substantial role. During exercise, fatty acids are released from adipose tissue and used as a source of
energy in aerobic respiration. In recovery, fatty acids are taken up by adipose tissue and converted
to triglycerides, a process that requires ATP. In addition, following prolonged exercise, there is a
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shift from carbohydrate to fat metabolism. Slightly more oxygen is required to extract the same
amount of energy from fats as from carbohydrates. The synthesis of proteins may also contribute to
EPOC.

8. Features of smooth muscle

The two types of smooth muscle are visceral and multiunit smooth muscle. Visceral
smooth muscle is located in the walls of most viscera (organs) of the body, including the digestive,
reproductive, and urinary tracts. Visceral smooth muscle occurs in sheets of internal organs and has
numerous gap junctions, which allow action potentials to pass directly from one cell to another. As
a consequence, sheets of smooth muscle cells function as a unit, and a wave of contraction traverses
the entire smooth muscle sheet. For this reason, visceral smooth muscle is also called single-unit
smooth muscle or unitary smooth muscle.
Multiunit smooth muscle occurs as sheets, such as in the walls of blood vessels; as small
bundles, such as in the pili muscles and the iris of the eye; and as single cells, such as in the capsule
of the spleen. Cells or groups of cells form many (multi) units that function independently of each
other because there are few gap junctions connecting the cells.
Structure of Smooth Muscle. Smooth muscle cells are smaller than skeletal muscle cells
and spindleshaped, with a single nucleus located in the middle of the cell. The actin and myosin
myofilaments are not organized as sarcomeres. Consequently, there are no myofibrils, and smooth
muscle does not have a striated appearance. The actin and myosin myofilaments in smooth muscle
are organized as loose bundles scattered throughout the cell (figure 8.18). The actin myofilaments
are attached to dense bodies in the cytoplasm and to dense areas in the plasma membrane.
Dense bodies and dense areas are considered to be equivalent to the Z disks in skeletal muscle.
Noncontractile intermediate filaments also attach to the dense bodies and dense areas, forming an
intracellular cytoskeleton. When actin myofilaments slide past the myosin myofilaments, the dense
bodies and dense areas are pulled closer together, resulting in contraction of the smooth muscle cell
(see figure 8.18). The dense areas of adjacent smooth muscle cells are connected so that the force of
contraction is transmitted from one cell to the next.

Excitation-Contraction Coupling in
smooth muscles. Smooth muscles contract when voltage-gated calcium channels cause calcium to
enter the cytosol from sarcoplasmic reticulum and from outside the cell. Calcium binds reversibly
with calmodulin and the calcium-calmodulin complex activates the enzyme myosin light chain
kinase. This enzyme catalyzes the phosphorylation of myosin crossbridges and starts crossbridge
cycle activity. The activity of another enzyme phosphatase removes phosphate groups from myosin
and inactivates myosin. In comparison to skeletal muscle, smooth muscle contraction takes longer
to initiate and terminate.
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Neural Regulation of Contraction . Smooth muscles are innervated by autonomic
neurons. The neurons can be sympathetic, parasympathetic or both. Autonomic neurons may excite
or inhibit smooth muscle cells. Sympathetic and parasympathetic neurons affect smooth muscle in
opposite ways. The smooth muscle may also relax or contract in response to the same type of
autonomic neuron depending upon differences in neurotransmitter receptors in different locations.
Autonomic neurons do not form synapses with specific cells but with groups of cells.
Neurotransmitter is released at varicosities (swellings) found along the length of the axon. This
causes a neighboring group of cells to contract together. Smooth muscle cells contract in groups
also because of gap junctions between cells that allow electrical signals to spread from one cell to
another.
Smooth muscle cells may respond to an action potential with a slow-twitch-like contraction.
But most smooth muscle cells respond to neural stimulation in a graded fashion with either
increasing or decreasing tension depending upon whether the neural stimulation is excitatory or
inhibitory.
Some smooth muscles display a resting degree of tension or tone even in the absence of
neural stimulation. Smooth muscle may also respond to the presence of hormones and mechanical
stretch. Some smooth muscle cells in single-unit smooth muscle may serve as pacemakers by
depolarizing on a regular basis to produce pacemaker potentials. These pacemaker potentials
cause smooth muscle cells to contract in unison. Pacemaker potential occur spontaneously but may
be regulated by neural input.

P.S. In this lecture, the illustrations from the free Internet resource Pearson Education (2011)
and the Seeley’s Principles of Anatomy and Physiology textbook by Philip Tate, Second edition,
2011, are used.