Muscle physiology

Physiology Unit
Kedir Endris (MSC)
 Muscular System Functions
• Body movement: -Most skeletal muscles are attached
to bones and are responsible for most body
movements including walking, running, or manipulating
objects with the hands.
• Maintenance of posture:-Skeletal muscles constantly
maintain tone, which keeps us sitting or standing erect
• Respiration:-Muscles of the thorax are responsible for
the movements necessary for respiration.
• Production of body heat:- When skeletal muscles
contract, heat is given off as a by-product. This released
heat is critical to the maintenance of body temperature
 Muscle Tissues
 Through their highly developed ability to contract, groups of
muscle cells working together within a muscle can produce
movement and do work.
 Controlled contraction of muscles allows
1. purposeful movement of the whole body or parts of the
body (such as walking or waving your hand),
2. manipulation of external objects (such as driving a car or
moving a piece of furniture),
3. propulsion of contents through various hollow internal
organs (such as circulation of blood or movement of
materials through the digestive tract), and
4. emptying the contents of certain organs to the external
environment (such as urination or giving birth).
 Types of muscles: 3 types (1)
1.Skeletal/voluntary muscles
Located attached to bones & moves skeleton
They are elongated, cylindrical and multinucleated cells,
They are striated muscle
They are voluntary muscle, controlled by somatic NS (SNS)
2. Cardiac muscle:
Muscle of the heart
They are striated, branched and mononucleated
They are involuntary, controlled by autonomous NS (ANS), drugs and hormones
Have the property of autorhythmicity and syncytium
3. Smooth muscles
 Located in the wall of hallow organs (GIT, blood vessels, uterus, urinary
bladder, Iris)
 They have non-striated appearance, mononucleated cells
 Involuntary muscle, controlled by ANS, drugs and hormones

 Have the property of autorhythmicity and syncytium

Types of muscles

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Types of muscles...cont’d

A. Striated muscles

B. Smooth muscles

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Characteristics of muscle:
• 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
Structure of Skeletal Muscle
• A single skeletal muscle cell, known as a muscle fiber, is relatively
large, elongated, and cylinder-shaped.
• A skeletal muscle consists of a number of muscle fibers lying parallel
to each other and bundled together by connective tissue
• The fibers usually extend the entire length of the muscle. 7
 Structural organization of skeletal muscle
Entire muscle

Muscle fascicles

Muscle fibers

Myofibrils

Myofilaments

– Contractile protiens (thin myofilament (actin) and thick

myofilament (myocine))
– Regulatory proteins (troponin and tropomyocine)

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Structure of skeletal muscles: Connective Tissue Covering
• Epimysium
– Surrounds entire muscle
• Perimysium
– Surrounds bundles of muscle fibers (fascicles)
• Endomysium
– Surrounds individual muscle fibers

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Components of a muscle fiber

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Fine Structure of the Skeletal
Muscle (1)
Motor end plate: contact surface
with axon terminal
Sarcolemma: muscle cell
membrane
Sarcoplasma: muscle cell
cytoplasm
– Has lots of mitochondoria
– Lots of glycogen granules to
provide glucose for energy
needs
– contains myofibrils,
sarcoplasmic reticulum,
myoglobin, glycogen and
creatin
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 Fine Structure of the Skeletal Muscle (2)
Myoglobin

It is iron containing protein in muscle cells that gives red coloration

to the lean meat

Function: to store and reserve oxygen for muscle metabolism

A muscle cell has two tubular structures

1. Transverse tubules (T tubules)

 Function: conduction of depolarisation

2. Longitudinal tubules (sER)

 Function: Ca2+ storage

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 Fine Structure of the Skeletal Muscle (3)
Myofibrils
Each muscle fiber contains rod like structures called myofibrils that
extend the length of the cell
They are basically long bundles of protein structures called myofilaments
and their actions give muscle the ability to contract
The myofilaments are classified as thick and thin filaments
There are also regulatory proteins that form a complex with the thin
myofilaments
Myofilaments
Have 3 components
1. Actin (thin myofilaments)
2. Myosin (thick filaments)
3. Troponin and tropomyosin (regulatory proteins)

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 Myosin structure (The Thick Myofilaments)
• A single myosin protein resembles 2 golf clubs whose shafts have
been twisted about one another
• About 300 of these myosin molecules are joined together to form a
single thick filament
• The head  forms cross bridges with the thin filaments
• Presence of the enzyme (ATPase) in the head  release energy for
contraction

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Actin structure (Thin Myofilaments)
• Formed by 3 different
proteins:
i. Globular (G) actins: bind to
myosin heads
ii. Tropomyosin: long, fibrous
molecule, extending over
actin, and preventing
interaction between actin
and myosin
iii.Troponin: binds reversibly
to calcium and able to move
tropomyosin away from the
actin active site.

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Note the relationship between the thin and thick filaments

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 • The myofibrils are organized
into a repetitive pattern called
The Sarcomere the sarcomere
– Myosin: thick filament
– Actin: thin filament
• Bands formed by pattern:
– A band: contains only thick
filaments (darkened)
– I band: contains only thin
filaments (Lighted)
• H zone: contains only thick
filaments
• Z line: area of attachment of the
actin fibers
• M line: Myosin fiber centers
• A stands for Anisotropic
• I stands for Isotropic

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 T-Tubules and the SR
• Each muscle fiber has many T-tubules
• Typically each myofibril has a branch of a T-tubule encircling it at each A-
I junction
• At each A-I junction, the SR will expand and form a dilated disc (terminal
cisterna)
• Each T-tubule will be flanked by a terminal cisterna
• This forms a so called triad consisting of two terminal cisternae and one T-
tubule branch

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 Muscle contraction: The Sliding Filament
Hypothesis
• Hanson and Haxley
– Proposed that the skeletal muscles shorten during contraction
because the thick and the thin myofilaments slide past one
another
– Their model is known as the sliding filament mechanism of
muscle contraction
– The thin filaments slide over the thick filaments
– This pulls the Z discs closer together
– When all the sarcomeres in a fiber do this;
• The entire fiber gets shorter which pulls the endomysium,
perimysium and epimysium come together to form tendon
attached to the bone.
• The sarcomere and the muscle fibers shortens.
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 Muscle contraction (The Sliding Filament Hypothesis)
• The sliding filament model
– Muscle shortening occurs due to the movement of the actin
filament over the myosin filament
– Formation of cross-bridges between actin and myosin filaments
– Reduction in the distance between Z-lines of the sarcomere

Here is what happens

as the filaments slide
and the sarcomere and
the muscle fiber shortens.
In the process of contraction,
what happens to the:
1. Distance btwn Z discs
2. Length of the A band
3. Length of the H zone
4. Length of the I band
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 Innervations of the Skeletal Muscle
• Each muscle is served by one nerve
– A bundle of axons carrying signals from the spinal cord to the
muscle
• With in the muscle, each axon will go its own way and
eventually branch into multiple small extensions called
telodendria
• Each telodendrium ends in a bulbous swelling known as the
synaptic end bulb
• The site of interaction b/n a neuron and any other cell is known
as a synapse.
• The synapse b/n a neuron and a muscle is known as the
neuromuscular junction (NMJ).
• A motor unit: is defined as a somatic motor neuron and all the
skeletal muscle fibers it innervates.

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 Motor Units
• When this neuron is stimulated, all
the muscle fibers it synapses upon
will be stimulated and will
contract as a unit
• The number of muscle fibers per
motor unit may be as high as
several hundred or as few as four.
– The smaller the motor unit, the
finer and more delicate the
movements.
– Extraocular muscles typically
have small motor units while
the large postural muscles have
large motor units

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 The Neuromuscular Junction
• The minute space between the synaptic end bulb and the
sarcolemma is known as the synaptic cleft.
• There is a depression in the sarcolemma at the synaptic cleft
known as the motor end plate.

• The synaptic end

bulb is filled w/
vesicles that
contain the
neurotransmitter,
acetylcholine.
• The motor end
plate is chock full
of acetylcholine
receptors,
nicotinic receptor. 23
 Transmission of Nerve Impulse at the NMJ
(Excitation) (1)
1. A nerve signal will arrive at the synaptic end bulb and this
will cause the ACh-containing vesicles to undergo
exocytosis.
2. ACh will diffuse across the synaptic cleft and bind to the
ACh receptors.
– These receptors are actually ligand-gated Na+ channels.
– The binding of ACh causes them to open.
3. Na+ will rush into the cell, making the local cell interior more
positive.
– This is known as depolarization.
– It is a local event!

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 Transmission of Nerve Impulse at the NMJ (2)
4. Adjacent to the motor end plate, the sarcolemma contains
voltage-gated ion channels.
– In order for these channels to open, the membrane must
depolarize from its resting value of -70mv to
approximately -55mv.
– This is the threshold
5. The degree of depolarization depends on how much Na+
influx occurs which in turn depends on how many Na+
channels were opened by binding Ach.
6. If the membrane fails to depolarize to threshold, nothing will
happen.

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Synaptic events

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 Characteristics of neuromuscular junction
• Transmission is unidirectional
• There is a single NMJ per muscle fiber
• The neurotransmitter is always acetylcholine (Ach)
Synthesis: Choline + Acetyl-COA = ACh by the action of
choline acetyl-COA transferase
Storage: Ach form a complex with ATP, packed in vesicles
Release: Released by Ca-dependent exocytosis
Metabolism: Metabolized by the action of ACh-Esterase
• The post junctional receptor is always nicotinic receptor
• The effect of Ach on NR is always excitatory producing
EPSP/end plate potential (EPP)
• It is fatigable due to depletion of ATP and NT storage

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 Mechanism of muscle contraction
(Excitation-contraction coupling) (1)
• When a muscle fibre membrane is depolarized, contraction of the
fibre follows.
• The process by which depolarization initiates contraction is called
excitation contraction coupling.
• It has several steps as follow:
1. Action potential initiated & propagated along the motor nerve fibre
and arrives at the end feet.
2. Opening of VG-Ca-channels and influx of Ca2+ to trigger the
release of Ach.
3. Ach released by Ca-dependent exocytosis and diffuse through the
synaptic cleft and binds to NR on post-junctional membrane.
4. Opening of ligand gated Na-channels and influx of Na+ to produce
EPP.
5. Spread of depolarization through the sarcolemma
6. Spread of depolarization through the T-tubules

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 Excitation-contraction coupling (2)
7. Depolarization of T-tubules stimulate SR to release Ca2+ into
sarcoplasm
8. Ca2+ binds to troponin-C
9. Ca2+ and troponin-C combination detaches troponin-I from the
active sites of actin
10. The detachment of troponin-I from actin displaces tropomyocin,
uncovering the active sites of actin filaments.
11. When the active site of actin exposed, the heads of myosin connect
to them, making cross-bridges b/n myosin and actin.
12. The ATPase enzyme on the myosin heads hydrolyze ATP into ADP
+ -P plus energy.
13. The released energy causes the movt of the head (power stroke)
towards the centre.
14. The head of myosin is charged with a new molecule of ATP and
then detached from actin leading to relaxation.
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 Mechanism of muscle relaxation
 It has the following steps
1. Following muscle contraction, Ca2+ is re-uptaken back into
SR by Ca-pump, this requires ATP.
2. Decreased Ca2+ in the sarcoplasm→ Ca2+ detaches from
troponin-C →Tropomyosin covers the active sites of actin.
3. Head of myosin charged with ATP, and detached from actin
 Therefore, muscle relaxation is an active process requiring
energy.
 Large amount of energy (ATP) is consumed during muscular
performance for the following activities:
1. To move the head of myosin (power stroke)
2. Active Ca2+ pump from sarcoplasm to SR
3. For Na-K-pump in the membrane
4. For muscle relaxation

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 Rigor Mortis
• This is known as “stiffness of death” w/c is a generalized locking in
place of the skeletal muscles that begins 3 to 4 hours after death and
completes in about 12 hours.
• Following death, the cytosolic concentration of Ca2+ begins to rise
• Dead cells cannot produce any more ATP, so actin and myosin, once
bound, cannot detach, because they lack fresh ATP.
• The thick and thin filaments thus stay linked together by the
immobilized cross bridges, leaving dead muscles stiff
• During the next several days, rigor mortis gradually subsides as the
proteins involved in the rigor complex begin to degrade.

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Rigor Mortis….

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Rigor Mortis….

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 Phases of the Muscle Twitch
• A twitch contraction is a brief contraction of all the muscle
fibers in a motor unit in response to a single action potential
in its motor neuron.
• recording of a muscle contraction, called a myogram
1. Latent Period
– Time b/n stimulus (time zero on the graph) and the
beginning of contraction.
– Includes all time required for excitation, excitation-
contraction coupling, and stretching of the series elastic
components.
– the muscle action potential sweeps over the sarcolemma
and calcium ions are released from the SR

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 Phases of the Muscle Twitch
2. Contraction time (upward tracing)
– The time from contraction onset until peak tension
develops
– repetitive power strokes arenoccurring, generating
tension or force of contraction
– averages about 50 msec, although this time varies,
depending on the type of muscle fiber.
3. Relaxation time (downward tracing)
– The time from peak tension until relaxation is complete
– Power strokes cease because the level of Ca2+ in the
sarcoplasm is decreasing to the resting level.
– usually lasts another 50msec or more

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 Effect of multiple successive stimuli on
muscle contraction
• The response of the whole
muscle to multiple successive
stimuli depends on the frequency
of stimuli applied as follow:
1. If high frequency stimuli are
applied and fall on the
contraction phase, the result is a
continuous contraction without
relaxation.
– This type of contraction is
called tetanic contraction or
tetanus.

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2. If the stimuli are of
moderate frequency just
below the minimum tetanic
frequency, and each
stimulus falls in the
relaxation phase, the result
is a series of contraction
with incomplete relaxation.
– This type of contraction Do not confuse this with the disease caused
is called clonic by the bacterium Clostridium tetani. Its
toxins prevent the normal inhibition of
contraction, clonus or muscle contractions as mediated in the
incomplete tetanus spinal cord. This leads to uncontrolled,
unwanted muscle contraction and
ultimately respiratory arrest.

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Summation and Tetanus
 Types of Contractions

• Contractions can be:

1. Isometric
• Iso= same, metr=measure
2. Isotonic
• Iso=same, ton=tension

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 Isotonic Contraction
• It is the type of contraction with no change in muscle tension
• There is shortening of the total Length of the muscle
• Occurs when contraction moves an object of moderate Wt
• Work is done in this type of contraction

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 Isometric Contractions
• It is the type of contraction w/o change in Lth
• Occurs when muscle contraction fails to move heavey objects
• No work is done in this type of contraction

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 Types of Skeletal Muscle Fibers
• Based on the velocity of shortening, major pathways used to
form ATP and fatigability, muscle fibers are classified into 3
types as

1. Type-I: Slow, fatigue-resistant, oxidative fibers. e.g. Soleus

muscle

2. Type-II: fast, fatigue-resistant, oxidative fibers. e.g.

Gastrocnemius

3. Type-III: fast, fatigable, glycolytic fibers. e.g. Lateral rectus

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 Slow oxidative (SO) fibers or red fibers:
• small in diameter
• appear dark red due to a large amount of myoglobin and
mitochondria
• generate ATP mainly by aerobic cellular respiration
• it is said to be “slow” because the contraction cycle
proceeds at a slower pace than in “fast” fibers.
• Very resistant to fatigue and are capable of prolonged,
sustained contractions.

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 Fast oxidative–glycolytic (FOG) fibers:
• Intermediate in diameter between the other two types.
• contain a large amount of myoglobin, and thus appear dark
red.
• can generate considerable ATP by aerobic cellular
respiration, which gives them a moderately high resistance
to fatigue.
• Because their glycogen content is high, they also generate
ATP by anaerobic glycolysis.
• These fibers are “fast” because they contract and relax
more quickly than SO fibers.

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 Fast glycolytic (FG) fibers or white fibers:
• largest in diameter
• contain the most myofibrils, and
• generate the most powerful and most rapid contractions.
• They have a low myoglobin content and few
mitochondria.
• FG fibers contain large amounts of glycogen and generate
ATP mainly by anaerobic glycolysis.
• They are used for intense movements of short duration,
but they fatigue quickly.

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 Myasthenia Gravis
• My=muscle, asthen=weakness, gravi=heavy
• It is the defect in the NMJ, characterized by easy fatigability of the
skeletal muscle.
• Results in progressive weakening of the skeletal muscles.
Possible causes
• Autoimmune disease where antibodies attack the NR on neuromuscular
junctions.
• High thymopoietin is another
• Decrease in quantity of Ach release
• Decrease in number of NR on neuromuscular junctions
• Decrease in post-junctional folds
• Increase in width of synaptic cleft
Treatment:
• Anticholinesterase: anticholinesterases such as neostigmine or
physostigmine.
– These decrease the activity of acteylcholinesterase.
• Steriods, which are immunosuppressants
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 Smooth Muscle
• Involuntary, non-striated muscle tissue
• Occurs within almost every organ, forming sheets, bundles, or sheaths
around other tissues.
• Cardiovascular system:
– Smooth muscle in blood vessels regulates blood flow through vital
organs. Smooth muscle also helps regulate blood pressure.
• Digestive systems:
– Rings of smooth muscle, called sphincters, regulate movement
along internal passageways.
– Smooth muscle lining the passageways alternates contraction and
relaxation to propel matter through the alimentary canal.
• Respiratory system, Urinary system, Reproductive system..etc are
organ system in our body contain smooth muscle

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 Smooth Muscle cont’d….
• Smooth muscle cells:
– Are smaller: 5-10um in diameter
and 30-200um in length
– Are uninucleate: contain one
centrally placed nucleus
– Lack any visible striations
– Lack T-tubules
– Have a scanty sarcoplasmic
reticulum
• Smooth muscle tissue is innervated by the autonomic nervous
system unlike skeletal muscle which is innervated by the
somatic nervous system (over which you have control)
• Only the endomysium is present.
• Neither perimysium nor epimysium.
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 Smooth Muscle
Contraction

• Myosin and actin are

present and crossbridge
formation powers
contraction, but the thick
and thin filaments do not
have the strict repeating
arrangement like that found
in skeletal muscle.
• There are no Z discs, instead
thin filaments are attached
to protein structures called
dense bodies which attach
to the sarcolemma.

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 Smooth Muscle
Contraction
• Begins with the opening of membrane
channels. Channels may be ligand-gated
(NTs, hormones, metabolites), voltage-
gated, or mechanically-gated (stretch).
• Channels will allow significant calcium
entry from the ECF. Remember smooth
muscle has little SR.
• Calcium binds to a regulatory molecule
called calmodulin and activates it.
• Activated calmodulin activates an enzyme
called Myosin Light Chain Kinase (MLCK).

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 Smooth Muscle
Contraction
• Activated MLCK will add a
phosphate group to the
myosin of the thick
filament. This enables the
myosin to interact with
actin.
– Tropomyosin is present but
not blocking actin’s myosin
binding sites
– Troponin is not present
• Contraction then ensues.

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 Types of Smooth Muscle
• Smooth muscle varies widely from organ to
organ in terms of:
– Fiber arrangement
– Responsiveness to certain stimuli
• Broad types of smooth muscle:
– Single unit (visceral)
– Multi unit

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 Single Unit Smooth Muscle
• More common
• Cells contract as a unit because
they are all connected by gap
junctions - protein complexes
that span the PM’s of 2 cells
allowing the passage of ions
between them, i.e., allowing the
depolarization of one to cause
the depolarization of another.
• Some will contract rhythmically
due to pacemaker cells that have
a spontaneous rate of
depolarization.

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 Single Unit Smooth Muscle
• Not directly innervated.
Diffuse release of
neurotransmitters at
varicosities (swellings
along an axon).
• Responsive to variety of
stimuli including stretch
and concentration changes
of various chemicals
• Found in the walls of the
digestive tract, urinary
bladder, and other organs

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 Multi-Unit Smooth Muscle
• Innervated in motor units
comparable to those of skeletal
muscles
• No gap junctions. Each fiber
is independent of all the
others.
• Responsible to neural &
hormonal controls
• No pacemaker cells
• Less common
• Found in large airways to the
lungs, large arteries, internal
eye muscles (e.g., the muscles
that cause dilation of the pupil)

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Cardiac Muscle
• Striated, involuntary muscle
• Found in walls of the heart
• Consists of branching chains
of stocky muscle cells. Uni-
or binucleate.
• Has sarcomeres & T-tubules
• Cardiac muscle cells are Notice the branching and the
joined by structures called intercalated disc, indicated
intercalated discs – which by the blue arrow.
consist of desmosomes and
gap junctions.
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