Physiology of Skeletal & Physiology

L1 – L2
Smooth Muscles Dr. Nawal 2019-2020

Physiology of Skeletal muscle

Structure
Skeletal muscle fiber represents a single cell of a muscle, each fiber is a thin, elongated
cylinder with rounded ends. Beneath it is cell membrane or sarcolemma, the cytoplasm or
sarcoplasm of the fiber contains many small, oval nuclei and mitochondria.

The sarcoplasm
o The sarcoplasm contains numerous, threadlike myofibrils that lie parallel to one
another.
o They contain two kinds of protein filaments, thick filaments composed of the
protein myosin, and thin filaments composed of protein actin.
o The arrangement of these filaments produces alterating light and dark striations of
skeletal muscle fiber.
o Myofibrils of each muscle fiber are suspended side by side in the muscle fiber.
o The spaces between the myofibrils are filled with intracellular fluid called
sarcoplasm, containing large quantities of potassium, magnesium, and phosphate,
plus multiple protein enzymes.
o Mitochondria that lie parallel to the myofibrils, supply large amounts of energy in
the form of adenosine triphosphate ATP.
o Within the cytoplasm is a network of membranous channels that surrounds each
myofibril and runs parallel to it sarcoplasmic reticulum.
o Set of membranous channels called transverse tubules (T-tubules), extends inward
as invaginations from the fiber’s membrane, and passes all the way through the
fiber.

Myosin
A myosin molecule is composed of two twisted protein strands with globular parts
called cross- bridges projecting outward along their lengths, many of these molecules
comprise a myosin filament.

Actin
An actin molecule is a globular structure with a binding site to which the cross-bridges
of the myosin molecules can attach. Many of these actin molecules, arranged together
in a double twisted strand (helix), form an actin filament.

 Two types of proteins, tropomyosin and troponin, associate with actin filaments.
• Tropomyosin molecules are rod- shaped, and occupy the longitudinal grooves
of the actin helix.
• Troponin protein which is a complex of three globular protein molecules:
o Troponin I: has strong affinity for actin.
o Troponin T: has strong affinity for tropomyosin.
o Troponin C: has strong affinity for Ca+ ion.

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 ✓ Troponin I &T complex is believed to attach the tropomyosin to the actin.
✓ Troponin C is believed to initiate the contraction process.
✓ Each tropomyosin has a troponin molecule attached to it is surface, forming a
tropomyosin-troponin complex.
✓ In the resting state, the tropomyosin strands physically cover the active sites of the actin
strands, so that interaction cannot occur between the actin and myosin to cause
contraction

Model of light and dark striations

A band: is dark, contains thick filaments (mostly myosin)
H band: is Light area at center of A band (area where actin and myosin don’t overlap)
I band: is light, contains thin filaments (only actin)
Z line/disk: At center of I band where actins attach
Sarcomeres: Are contractile units of skeletal muscle consisting of components between 2 Z
discs
M lines: are structural proteins that anchor myosin during contraction
Titin: is elastic protein attaching myosin to Z disc that contributes to elastic recoil of
muscle

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 Titin Filamentous Molecules.
The side-by-side relationship between the myosin and actin filaments is achieved by a large
number of filamentous molecules of a protein called titin. Also, because it is filamentous, it is
very springy. These springy titin molecules act as a framework that holds the myosin and actin
filaments in place.

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 • The site where the nerve fiber and muscle fiber meet is called neuromuscular junction
(myoneural junction).
• There, the muscle fiber membrane is specialized to form a motor end plate, where nuclei
and mitochondria are abundant, and the sarcolemma is extensively folded.
• The membrane of nerve fiber and the membrane of the muscle fiber are separated by a
small gap called the synaptic cleft.
• The cytoplasm at distal ends of the nerve fibers is rich in mitochondria and contains many
tiny vesicles (synaptic vesicles) that store chemicals called neurotransmitters.
• Each muscle fiber receive a single axon terminal from a somatic motor neuron.
• The motor neuron stimulates the muscle fiber to contract by liberating acetyl choline at
the neuromuscular junction.
• A motor neuron, together with all of the muscle fibers that it innervates is known as a
motor unit.

Electrical properties of skeletal muscle

Skeletal muscle is an excitable tissue, when it is stimulated it will cause action potential as
muscle impulse.

 The differences of action potential of skeletal muscle from that of nerve action potential:
1. RMP (- 90mv).
2. Firing level is (- 60mv).
3. Duration of muscle impulse is about (2-4 ms).
4. It will not pass in after hyper polarization period, even in repeated stimuli.
✓ The potential of muscle can be recorded during contraction and this record known as Electro
myograph (EMG), which record the algebraic summation of action potential of all muscle
fibers.

Contractile property of skeletal muscle

• When muscle is stimulated, it contracts and after the contraction, and when there is
no stimulus, it relax.
• The contraction is done by shortening in length, but return to it is original length in
relaxation.
• The muscle cannot contract without stimulus, this is called: Excitation- contraction
coupling, this mean that there is no contraction without excitation of the muscle.

 Mechanism of skeletal muscle contraction

Sliding filament theory of muscle contraction:
• Suggests that the head of a myosin cross-bridge can attach to an actin binding site
and bend slightly, pulling the actin filament with it.
• Then the head can release and combine with another binding site farther down the
actin filament.
• The cross-bridges of myosin filaments contain the enzyme ATPase, which catalyzes
the breakdown of ATP to ADP and phosphate, and release energy that provides the
force with which a cross-bridges pulls.
• This cycle can repeated over and over.

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 Muscle fiber contraction:
1. The distal end of a motor neuron release acetylcholine.
2. Acetylcholine diffuses across the gap at the neuromuscular junction.
3. The sarcolemma is stimulated, and a muscle impulse travels over the surface of
the muscle fiber and deep into the fiber through the transverse tubules and
reaches the sarcoplasmic reticulum.
4. Calicum ions diffuse from the sarcoplasmic reticulum into the sarcoplasm and
bind to troponin molecules.
5. Tropomyosin molecules move and expose specific sites on actin filaments.
6. Actin and myosin filaments form linkages.
7. Actin filaments are pulled inward by myosin cross-bridges.
8. Muscle fiber shortens as a contraction occurs.

Muscle fiber relaxation:

1. Acetylcholinesterase enzyme which present at the neuromuscular junction on
the membrane of the motor end plate, decomposes acetylcholine, and the
muscle fiber membrane is no longer stimulated.
2. Calcium ions are actively transported into sarcoplasmic reticulum.
3. Linkages between actin and myosin filaments break.
4. Troponin and tropomyosin molecules inhibit the interaction between myosin
and actin filaments.
5. Actin and myosin filaments slide apart.
6. Muscle fiber relaxes and it is resting state is reestablished.
7. When a muscle fiber is at rest, tropomyosin-troponin complexes block the
binding sites on the actin molecules and thus prevent the formation of linkages.

✓ Both contraction and relaxation are an active process and need energy.
✓ Fatigue of the skeletal muscle is due to the ATP source is lost in the muscle with
continues stimulus. There is depletion of muscle glycogen due to the interruption of
blood flow through muscle contraction, and loss of nutrient supply especially loss of O2.
Therefore, muscle stop contractions.

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  Muscle hypertrophy: forceful muscular activity cause the muscle size to increase.
o Most hypertrophy result from increase in the diameter of muscle fiber
o and partly due to hyperplasia (increase the number of muscle fiber).

 Muscle atrophy: results from non-using muscle for prolonged period of time, also result
from muscle denervation.

Energy sources
ATP provides immediate energy for muscle contractions from 3 sources

1. Creatine phosphate
During resting conditions stores energy to synthesize ATP

Direct phosphorylation
o Muscle cells contain creatine phosphate (CP)
o CP is a high – energy molecule.
o After ATP is depleted, ADP is left.
o CP transfers energy to ADP, to regenerate ATP
o CP supplies are exhausted in about 20 seconds.

2. Anaerobic respiration
Occurs in absence of oxygen and results in break down of glucose to yield ATP and lactic
acid

Anaerobic glycolysis
o Reaction that breaks down glucose without oxygen
o Glucose is broken down to pyruvic acid to produce some ATP
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 o Pyruvic acid is converted to lactic acid.

3. Aerobic respiration
Requires oxygen and breaks down glucose to produce ATP, carbon dioxide and water.
More efficient than anaerobic

Aerobic glycolysis
o Series of metabolic pathways that occur in the mitochondria
o Glucose is broken down to carbon dioxide and water, releasing energy
o This is a slower reaction that requires continuous oxygen.

Types of contractions:
The muscle contains an elastic element, and can do both types of contractions:

Isotonic contraction (constant tension)

means the tension developed during contraction is constant, while the length of muscle is
changed e.g. walking.

Isometric contraction (constant length)

tension is changed while the length is constant e.g. standing, pushing an un movable thing.
So, the muscle contract isometrically by shortening the contractile elements, and
elongation of elastic component, so the length of entire muscle is constant.

✓ In isometric contraction, the muscle does not work, while in isotonic it works, so that
isotonic contraction needs more energy than isometric contraction, it does work, so isotonic
contraction is stronger than isometric contraction (need more energy).

 Relationship between the length of muscle fiber and it is tension during contraction
• Each muscle have got a constant length and this called resting length, depend on age,
sex, growth, and it is constant for each muscle.
• If the length of the muscle is decrease or increase than resting length, the tension will
decrease.
• So, the relationship between the tension of muscular fiber is inversely proportional with
muscle length.

➢ The reason of this relationship is due to:

1. If the muscle length increase, the cross bridges (which are responsible for muscle
tension), will become away from the actin filaments, and cannot pull actin, and the
tension produced by few numbers of cross bridges sharing in the sliding of actin on
myosin.
2. In shortening of muscle fiber, the actin filament will overlap on each other, and some
cross bridges fail to reach the active sites on the actin filaments, and decrease the
tension.

✓ In conclusion: Increasing or decreasing the muscle fiber length, will decrease the tension,
due to decrease the number of cross bridges sharing in the tension formation.

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 Summation of contraction
• The muscle converts the electrical energy to mechanical energy, so summation means
adding together of individual contractions.
• In the muscle, a group of muscle fibers supplied by a single axon, called motor unit.
• If we apply a stimulus to skeletal muscle, we gain simple muscle twitch. (muscle
contraction followed by relaxation).

Spatial Summation (multiple-motor units summation)

o If we increase the strength of continuous stimulus, increasing the number of motor
units contracting by increase the magnitude of stimulus.
o (2 impulses/ms < 3 impulses/ms < 4 stimulus/ ms).
o There will be increase in the number of motor units contractions.

Temporal Summation (Wave summation)

o If the duration of simple muscle twitch is 1ms, so if we apply 2 stimulus/ms (same
strength of stimulus),
o the second contraction stronger than the first one, and so on, because the Ca+
remain in the sarcoplasm, and the muscle not relax ( no refractory period), the
curve will continue as a wave until we stop stimulus.
o There will be increase in the number of contractions for the same motor units in a
constant period, the tension will increase because there will be accumulation of Ca+
in the sarcoplasm, not return to sarcoplasmic reticulum.
o When there is continues contractions without relaxations, the condition called
complete tetanus.

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Physiology of smooth muscle
They are called Unstriated, involuntary muscle

Types of smooth muscle

1. Visceral smooth muscle (single unit smooth muscle)
o the muscle fibers are spindle- shaped cells that are held in close contact by gap
junctions, and attached to each other to present in a sheet
o so that if we give stimulus to one muscle fiber, the stimulus will spread to other
muscle fibers, so it has syncytiam character, so that the whole sheet will contract as
one unit
o therefore, the visceral smooth muscle also called single unit smooth muscle, which
form about 99% of the smooth muscles in the body
o the contraction is called syncytial contraction.

2. Multi units smooth muscle.

The muscle fibers each one contracts individually, and have a single axon e.g. the muscle
surround the iris of the eye to control the opening of the pupil.

 IN SMOOTH MUSCLES:
1. There is no well-developed sarcoplasmic reticulum.
2. Actin and myosin filaments are distributed randomly.
3. Has no troponin, but contain calmodulin, which got the same function of troponin C in
skeletal muscle.
4. The myosin is the same but it got an enzyme called myosin light chain kinase, (convert
ATP→ ADP +energy), and it also got cross bridges.

Electrical properties of smooth muscle

Resting membrane potential:
• The resting membrane potential of smooth muscle is un stable and fluctuated and
vary from (-55mv to -50mv)
• there is unstable Na+-K+ pump and it can be hyper active or hypo active
• i.e. waxing (activation) or wanning (inhibition) of Na+- K+ pump lead to slow wave
rhythm, that occur at regular intervals and considered as electro tonic potential.

 SMOOTH MUSCLE UNDER NORMAL CONDITION CAN PRODUCE:

o Action potential by nerve stimulus.
o Spontaneous action potential without stimulus because of prolonged inhibition of Na+-
K+ pump that may cause the potential to reach(-45mv) which is the firing level, and cause
action potential spontaneously.

The myoneural junction of smooth muscle

the smooth muscle receives nerve impulses from: Sympathetic and parasympathetic nerve
supply, so the neurotransmitters either:

1. excitatory
o (acetyl choline) in parasympathetic stimulation.
o Acetyl choline will attach to receptors and lead to opening of Na+ channels, Na+
will enter the cell and initiate action potential.

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 2. inhibitory
o (nor adrenaline or nor epinephrine) in sympathetic stimulation.
o There will be opening to Cl- channels, and Cl- will enter to the cell
o or opening of K+ channels and K+ get outside the cell,
o both cause hyper polarization, and inhibition to the muscle.

Muscle contraction
 Smooth muscle contraction resembles skeletal muscle contraction in a number of ways,
o both mechanisms reflect reactions of actin and myosin
o both are triggered by membrane impulses and release of calcium ions
o both use energy from ATP molecules.

 There are significant differences:

o smooth muscle fibers lack troponin , instead, it use a protein called calmodulin,
which bind to calcium ions released when it is fibers are stimulated, thus actin-
myosin contraction mechanism activating.
o The calcium necessary for smooth muscle contraction diffuses into the cell from the
extra cellular fluid.
o Smooth muscle is slower to contract and slower to relax than skeletal muscle, and
can maintain a forceful contraction for a longer time with the same amount of ATP.
o Smooth muscle fibers can change length without changing tautness; stretching of
smooth muscle fibers can also trigger contractions. The ability of smooth muscle to
make it is tension constant despite the change in smooth muscle fibers length called
plasticity.

Types of smooth muscle contraction:

1. Rhythmic contraction (rhythmicity):
a pattern of repeated contractions, this caused by self- exciting fibers that deliver
spontaneous impulses that transmitted from cell to cell and rhythmicity responsible
for the wavelike motion called peristalsis (alterate contraction and relaxation) e.g. in
GIT.

2. Tonic contraction:
continuous contraction of smooth muscle, this type is found in the sphincters and wall
of blood vessels.

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