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11/15/16
Collin College
BIOL 2401
Muscles & Physiology I
1
TYPES OF MUSCLE
Cardiac muscle
• heart muscle tissue
• striated but involuntary
• includes a pacemaker system that causes the heart to beat
Smooth Muscle
• located in the walls of hallow internal structures
• non-striated (therefore appears as "smooth" )
• involuntary
Skeletal muscle
• attached primarily to bone
• striated
• voluntary
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TYPES OF MUSCLE
3
FUNCTION OF MUSCLE
• Produces motion
• involved in the integrated functioning and
movement of bones and joints via skeletal
muscle
• less noticeable is the motion of the heart and
that of the internal organs such as gut
• Maintain posture
• Stabilizes joints
• Supports soft tissues and Regulates organ volume
• Generates heat : muscle contraction generates 80-85
% of body heat
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CHARACTERISTICS OF MUSCLE
• Excitability : ability to respond to stimuli (chemical) by
producing electrical signals (current)
• Contractility : ability to shorten and thicken (contract),
thereby producing force
• Extensibility : ability to stretch without damage to the
tissue (opposing muscle is always stretched
when primary muscle contracts)
• Elasticity: ability to return to its original length and
shape after being stretched
5
CHARACTERISTICS OF MUSCLE
Skeletal muscles attach to bones across joints
Skeletal muscles are organized in agonistic/
antagonistic pairs.
A muscle can shorten and pull on a bone, but
cannot push a bone away .
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CHARACTERISTICS OF MUSCLE
Prefix Terminology with respect to muscles.
Myo - : refers to muscle
• myo-cyte
• myo-fillament
Sarco - : means flesh
used in for example
• sarcolemma
• sarcoplasma
• sarcoplamic reticulum
Cardio - : refers to the heart
7
Anatomy of Skeletal Muscle
Skeletal muscles are
attached to the skeleton by
tendons.
A muscle bundle is made
out of groups containing
many individual muscle
cells. Such groups are
called fascicles.
A single muscle cell is
called a muscle fiber.
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Anatomy of Skeletal Muscle
Epimysium
Bone Epimysium
Perimysium
Endomysium
Tendon
(b)
Muscle fiber
in middle of
a fascicle
Blood vessel
Fascicle
(wrapped by perimysium)
Endomysium
(between individual
muscle fibers)
Perimysium Fascicle
(a)
Muscle fiber
9
Anatomy of Skeletal Muscle
Figure 10-1 The Organization of Skeletal M uscles (Part 3 of 3).
Epimysium :
• surrounds the whole muscle
• made from dense regular CT
• attaches to periosteum of bone
Perimysium
• surrounds the fascicles
Endomysium
• surrounds each muscle fiber
• made from areolar CT
Muscle Fiber (cell)
Capillary
Myofibril
Endomysium
Sarcoplasm
Epimysium
Blood vessels
and nerves
Mitochondrion
Myosatellite
cell
Sarcolemma
Nucleus
Tendon
Axon of neuron
Endomysium
Perimysium
10
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Anatomy of Skeletal Muscle
• Each muscle is served by one nerve, an artery,
and one or more veins
• Each skeletal muscle fiber is supplied with a
nerve ending that controls contraction
• Contracting fibers require continuous delivery
of oxygen and nutrients via arteries
• Wastes must be removed via veins
11
Skeletal Muscle Fibers (cells)
Muscle cells originate from the fusion of embryonic
cells called myoblasts. Each cell is thus a syncytium
produced by fusion of embryonic cells
They are thus multinucleate are in general slender and
long ( 100 um wide, sometimes 12 inches long)
Satellite cells are unfused myoblast cells that remain
active in assisting the regeneration of damaged muscle
fibers
12
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Skeletal Muscle Fibers (cells)
13
Skeletal Muscle Fibers (cells)
• Each muscle fiber (cell) is a long, cylindrical cell with
multiple nuclei just beneath the sarcolemma
• Fibers are 10 to 100 mm in diameter, and up to hundreds
of centimeters long
• Sarcoplasm has numerous glycosomes (glycogen
containing bodies) and a unique oxygen-binding protein
called myoglobin
• Fibers contain the usual organelles such as
mitochondria, sarcoplasmic reticulum and special
structures called myofibrils and T tubules.
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Micro-Anatomy of Skeletal Muscle
Each skeletal muscle fascicle is typically composed of many
muscle fibers (cells).
Each muscle fiber (=muscle cell) is packed with long cylindrical
myofibrils.
Each myofibril in turn is made out of smaller protein based
structures called myofilaments .
The myofilaments are organized into sarcomeres, which are the
contractile units of a muscle cell.
15
Micro-Anatomy of Skeletal Muscle
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MyoFibrils
Sarcolemma
Muscle
cell
Mitochondrion
Dark A band
Myofibril
Light I band
Nucleus
• Myofibrils are densely packed, rodlike contractile
elements
• They make up most of the muscle volume
• The arrangement of myofibrils within a fiber is such that a
perfectly aligned repeating series of dark bands (the A
bands) and light bands (the I bands) are evident
17
Myofibrils & Myofilaments
Each myofibril is made from
bundles of proteins called the
myofilaments.
There are two major
proteins involved :
• Actin : they form the thin
filaments
• Myosin : they form the
thick filaments
These proteins within the myofibrils are the actual
contractile elements of a muscle
18
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Sarcomeres
Myofibril
• Each myofibril is made up of around 10,000 sarcomeres
arranged in series (back to back)
• The sarcomere is smallest contractile unit of a muscle
• It is the region of a myofibril between two successive Z
discs
• Composed of myofilaments made up of the contractile
19
proteins actin, mysosin and other proteins.
Sarcomeres : the unit of contraction
• Z-disc (line): coin-shaped sheet of proteins that anchors
the thin filaments and connects myofibrils to one another
• I-band (light band): area around both sides of the z-disc;
no mysosin occurs here.
• Thin filaments: run the length of the I band and partway
into the A band
• A-band (dark Band): this is the darker middle region of a
sarcomere. Here thick and thin filaments overlap except
for the
• H zone: lighter mid-region of the A-band where thin
filaments do not reach
• M line: center of the A-band with some thicker proteins
20
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Sarcomeres : the unit of contraction
Thin (actin)
filament
Thick (myosin)
filament
Z disc
I band
H zone
A band
Sarcomere
Z disc
I band
M line
(c) Small part of one myofibril enlarged to show the myofilaments
responsible for the banding pattern. Each sarcomere extends from
one Z disc to the next.
Notice the Titin proteins
anchoring and stabilizing the thick
filaments to the Z discs.
Sarcomere
Z disc
M line
Z disc
Thin (actin)
filament
Elastic (titin)
filaments
Thick
(myosin)
filament
(d) Enlargement of one sarcomere (sectioned lengthwise). Notice the
myosin heads on the thick filaments.
21
Structure of Thin Filaments
The thin filament (F-actin) called actin is a polymer of G-actin
molecules.
Each G-actin molecule has a binding site to which a myosin
head can bind
22
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Structure of Thin Filaments
The binding sites on actin are covered by a tropomyosin filament.
The tropomyosin filament is attached to the actin chain by means
of a Troponin complex. In relaxed skeletal muscle, tropomyosin
blocks the myosin head (also called cross-bridge) binding site on
actin.
When calcium ions bind to troponin , the troponin complex
pulls tropomyosin away from the cross-bridge binding site.
23
Structure of Thick Filaments
The thick filament called myosin is actually a polymer of myosin
molecules
Each has a flexible cross-bridge (head) with ATPase activity and
with a binding site for actin.
24
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Structure of Thick Filaments
25
Structure of Thick Filaments
Myosin head
26
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Structure of Myofibril and Sarcomere
Each thick filament is surrounded
in a hexagonal pattern by 6 thin
filaments.
27
Sarcolemma and Skeletal Muscle
The cell membrane of a Skeletal muscle is called sarcolemma
It is an excitable membrane ; has similar properties as a
nerve cell membrane
• Has a resting membrane potential
• Has the ability to generate action potentials along
that membrane (what does this implicate ? )
IN nerve tissue, the purpose of the action potential is guide the
electrical activity towards the axon terminal end-point, where it
results in the release of Neurotransmitters !
The purpose of the action potential on a muscle cell is to start the
process of contraction.
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T-tubules and SarcoPlasmic Reticulum
Skeletal Muscle contraction is started by the release of
calcium from the internal stores, the Sarcoplasmic
Reticulum (SR)
Problem : SR is located within the cell and the Action Potentials run
along the plasma-membrane !
-----++++
Act. Pot.
S.R
Contains [Ca2+]
Motor neuron
29
T-tubules and Sarcolemma
The action potential has to be guided to the inside of the cell to
‘reach out and touch’ the SR .
S.R
Contains [Ca2+]
This is accomplished by narrow membrane pits, tubular
extension of the plasma membrane that extend deep within the
sarcoplasma. These are called the T-tubules !
30
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T-tubules and SarcoPlasmic Reticulum
• T-tubules dip into the cell at the Z-discs
• Smooth endoplasmic reticulum of a muscle cell =
• sarcoplasmic reticulum
• encircles the contractile elements of the cell around each
sarcomere with interconnecting tubules that run longitudinally
• Interconnecting sacs of the SR run on either side of the T-tubules =
terminal cisternae or end sacs
• Combination of T-tubules and a pair of surrounding terminal
cisternes = Triad system
• Calcium is released from the SR via special Calcium-release
channels that respond to a voltage change
31
T-tubules and Sarcolemma
Terminal cisterna
Sarcolemma
Sarcoplasm
Myofibrils
Triad Sarcoplasmic
reticulum
T tubules
32
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T-tubules and Sarcolemma
Myofibril
Surrounded by:
Sarcoplasmic
reticulum
Consists of:
Sarcomeres
(Z line to Z line)
Since each sarcomere is within 2 triad systems with SR, an action
potential will release Calcium around each sarcomere, reducing the
diffusion distances and making the action of action quick and
effective.
33
Aspect of Contraction
Contraction of a muscle fiber
• Occurs when the myosin heads latch on to the actin
filament. Only possible when calcium is present to
unblock the binding sides.
• The mysosin cross bridges then pull on actin.
• This causes the actin filaments to slide inwards and
to pull the z-line towards each other
• This sliding results in the sarcomere to shorten without
altering the length of actin or myosin filaments
Called the sliding filament theory
34
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Aspect of Contraction
During Contraction and shortening the myofilaments ( thick and thin
filaments) do not shorten ! THEY SLIDE OVER EACH OTHER .
• The sarcomere shortens
• The A bind remains the same size - The I band shortens
A band
I band
35
Aspect of Contraction
Requirements for Skeletal Muscle Contraction
1.
Activation = neural stimulation via motor neuron and
release of N.T. at a neuromuscular junction
2. Excitation-contraction coupling:
– Generation and propagation of an action potential
along the sarcolemma
– Final trigger: a brief rise in intracellular Ca2+ levels
via release from the Sarcoplasmic Reticulum
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NeuroMuscular Junction
• Area where somatic motor neuron (axon) and skeletal muscle cells
make contact
• The motor end plate is the surface of the muscle cell where the
synapse occurs.
• As a rule, each muscle fiber (cell) has only one NMJ but one motor
neuron can activate many cells via collateral branches.
• Synapse is between the motor neuron axon on one side and the
motor endplate on the other side
• ACh is the neurotransmitter and the motor endplate carries ACh
receptors
37
Events at NMJ
• Release of ACh is triggered by an AP and results in opening of
voltage gated Ca-channels in the axon terminal of the motor
neuron.
• Binding of ACh at the motor endplate opens up chemically gated
Na-channels (nicotinic ACh receptor)
• This triggers a local de-polarization (graded potential) that
reaches outside of the NMJ area
• Outside the NMJ, voltage gated Na-channels respond to this
graded depolarization and open, triggering an Action
potential along the sarcolemma
38
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NeuroMuscular Junction
Myelinated axon
of motor neuron
Action
potential (AP)
Axon terminal of
neuromuscular
junction
Nucleus
Sarcolemma of
the muscle fiber
1 Action potential arrives at
axon terminal of motor neuron.
3
Ca2+
Ca2+
2 Voltage-gated Ca2+ channels
open and Ca2+ enters the axon
terminal.
Synaptic vesicle
containing ACh
Mitochondrion
Axon terminal
of motor neuron
ACh relesed into synaptic cleft area
Synaptic cleft
Fusing synaptic
vesicles
39
NeuroMuscular Junction
Axon terminal
Open Na+
Channel
Na+
Synaptic
cleft
ACh
ACh
Na+ K+
Na+ K+
++
++ +
+
Closed K+
Channel
K+
Action potential
6
+
+ +++
+
4 ACh binds to and opens nicotinic Na-channel
5 local depolarization: generation of the
40
Sarcoplasm of muscle fiber
end plate graded potential on the sarcolemma
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Sarcolemma Action Potential
Depolarization
due to Na+ entry
Na+ channels
close, K+ channels
open
Repolarization
due to K+ exit
Na+
channels
open
Threshold
K+ channels
close
41
Excitation-Contraction (E-C) Coupling
• Excitation-Contraction coupling is the sequence of
events by which transmission of an AP along the
sarcolemma leads to sliding of the myofilaments
• There is an initial latent period: this is the time
between AP initiation and the beginning of
contraction
– Time when the molecular/cellular aspects of E-C
coupling events occur
42
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Steps in (E-C) Coupling
Steps in
E-C Coupling:
1 Action potential is
propagated along the
sarcolemma and down
the T tubules.
Voltage-sensitive
tubule protein
Sarcolemma
T tubule
Ca2+
release
channel
2 Calcium
ions are
released.
Terminal
cisterna
of SR
43
Ca2+
Steps in (E-C) Coupling
Actin
Ca2+
Troponin
Tropomyosin
blocking active sites
Myosin
3 Calcium binds to
troponin and removes
the blocking action of
tropomyosin.
Active sites exposed and
ready for myosin binding
4 Contraction begins
Myosin
cross
bridge
44
The aftermath
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Muscle fiber Contraction
• Starts when calcium binds to troponin, allowing tropomyosin
to shift out of the way and un-block the myosin head binding
sites.
• ATP will now provide the energy so that the myosin heads
pull back and forth on the actin strands, creating the sliding of
thin over thick filaments
• The pulling of myosin heads on actin occurs via cross bridge
formations
• The direction of the pull is towards the middle of each
sarcomere
• Each mysoin head will cycle back and forth like a rower in a
rowboat as long as calcium and ATP is available in the
cytoplasm
45
Muscle fiber Contraction: Powerstroke
The powerstoke occurs when the
myosin head actually pulls on actin.
Actin
Myosin
cross bridge
It occurs when the myosin head lets
ADP ATP ( ADP and Pi)
go of hydrolyzed
ADP
Pi
Thick filament
1 Cross bridge formation.
The binding of an ATP molecule to the
myosin head, the energizing of the myosin
head by splitting ATP and the release of that
energy via the powerstroke, are very similar
to putting an arrow into a bow and putting
tension on the bowstring. The powerstroke is
then similar to letting the arrow fly.
ADP
Pi
46
2 The power (working) stroke.
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M yosin head
(high-energy
configuration)
ADP
Pi
1 M yosin head attaches to the actin
m yofilam ent, form ing a cross bridge.
Thin filam ent
ATP
hydrolysis
4
ADP
ADP
Thick filam ent
Pi
2
As ATP is split into ADP and P i, the m yosin
head is energized (cocked into the high-energy
conform ation).
Inorganic phosphate (P i) generated in the
previous contraction cycle is released, initiating
the power (working) stroke. The m yosin head
pivots and bends as it pulls on the actin filam ent,
sliding it toward the M line. Then ADP is released.
ATP
ATP
M yosin head
(low-energy
configuration)
3 As new ATP attaches to the m yosin head, the link between
m yosin and actin weakens, and the cross bridge detaches.
47
Muscle fiber Contraction: Powerstroke
• The important aspect is that ATP needs to bind to the mysoin head
in order for the mysoin head to detach from the actin
• The splitting of ATP into ADP and Pi provides the potential
energy by snapping the head back into a potential powerstoke
position. (like the pulling on the string of a bow to transfer the
energy into the string as potential energy)
• During a single contraction, about 50% of the mysoin heads are
puling while 50% are re-setting themselves
• A single sarcomere does not have to shorten much in order to get
a muscle group to shorten 1 cm ( for ex: if a muscle cell has 10,000
sarcomeres one after another, how much does each need to shorten ?)
48
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End of a Single Contraction: Relaxation
• a single nerve impulse needs to correlated with a single muscle
contraction
• released ACh in the synaptic cleft of the NMJ diffuses away AND is
quickly destroyed by AcetylCholine-esterase.
• this prevents continued muscle stimulation in the absence of nerve
impulses.
49
End of a Single Contraction: Relaxation
• In addition, strong Ca2+ pumps
operate at the SR level : from
the moment Ca2+ floods the
cell, they start pumping it back
into the SR
• Thus the cell only sees a brief
increase in Ca2+ : when calcium
vanishes, the binding sites on
actin become blocked again and
the contraction stops !
• The SR also contains special
proteins that bind Calcium strongly
( Calsequestrin) : This increases
the holding capacity for Calcium in
the SR and facilitates the reuptake of Calcium
50
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Excitation-Contraction Problems
• Duchenne’s Muscular dystrophy
• genetically inherited disease (only males affected)
• degenerative muscle weakness, paralysis and cardiac
problems
• usually die before age 20
• Related to lack of protein dystrophin
• Protein is suspected to play a role in calcium regulation
and stability of sarcomeres
• Myastenia Gravis
• Results from progressive loss of ACh receptors
• Due to autoimmune response attacking the receptors
• Botulism
• Results from consumption of contaminated canned food
progressive loss of ACh receptors
• Toxin prevents release of Ach (results in paralysis)
51
Excitation-Contraction Problems
• Curare
• binds to nicotinic receptors
• it thus blocks the ACh receptor:
no muscle contraction
• Organophosphates :
• pesticides, nerve gas
• inhibit ACh-esterase
• maintained depolarization
• maintained contraction and no relaxation
possible ( think what it will do to your
diaphragm)
52
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ATP versus Calcium Supply
Of the two important molecules for muscular
contraction, ATP and Calcium , which one
would be the fastest in short supply ?
53
Function of ATP
54
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Rigor Mortis
Following the death of an organism, cellular homeostasis
and integrity breaks down
• No circulation, no oxygen supply to tissues
• No mitochondrial activities, no ATP production
• Calcium leaks into the cell and cannot be pumped
out
• Binds to troponin ; tropomyosin shifts out of
position
• Myosin binds to actin
• But there is no ATP for the power stroke or to
release myosin from actin
• Muscles become “locked “ in place at the thinthick filament level
55
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