Muscle Physiology

• Muscle is one of our 4 tissue types

• Found being combined with nerves, blood
vessels, and various connective tissues.
• Muscles are quite complex and are marvel
of both biology and physics.

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 Muscle Functions
1. Produces Movement
o Movement of body parts
o Movement of blood throughout the body
o Movement of lymph through the lymphatic vessels
o Movement of food through the GI tract
o Movement of bile out of the gallbladder into the digestive tract
o Movement of urine through the urinary tract
o Movement of semen through the male and female reproductive
tracts
o Movement of a newborn through the birth canal

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 Muscle Functions
2. Maintenance of posture
o Muscle contraction is constantly
allowing us to remain upright.
o The muscles of your neck keep your
head up right now.
o As you stand, your leg muscles keep
you on two feet.
3. Thermogenesis
o Generation of heat. Occurs via
shivering – an involuntary contraction
of skeletal muscle.

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 Muscle Functions
4. Stabilization of joints

o Muscles keep the tendons that cross

the joint nice and firm

o This does a wonderful job of

maintaining the integrity of the
joint.

All the things muscles do fall under one of these 4 categories.

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3 Types of Muscle Tissue

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 Three Types of Muscle Tissue
 Skeletal Muscles
 Striated
 Multi-nucleatd
 Controlled by somatic nervous system (voluntary)

 Cardiac Muscle
 Striated
 Mono-nucleated
 Controlled by ANS (involuntary)
 Smooth Muscle
 Non-striated
 Mono-nucleated
 Controlled by ANS (involuntary) 6
 Characteristics of Muscle Tissue
1. Excitability
 The ability to receive and respond to a stimulus

 In smooth muscle, the stimulus could be a neurotransmitter, a

hormone, stretch, pH, Pco2, or Po2.

 In cardiac muscle, the stimulus could be a neurotransmitter, a

hormone, or stretch. Also autorhythmic

 In skeletal muscle, the stimulus is a neurotransmitter released by

a neuron only.

 The response is the generation of an AP that travels along the plasma

membrane of the muscle cell.
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 Characteristics of Muscle Tissue
2. Contractility
The ability to shorten and become thicken forcibly
when adequately stimulated.
This is the hallmark of muscle tissue.
3. Extensibility
–The ability to be stretched
4. Elasticity
–The ability to recoil and resume original length and
size after being stretched or contracted.

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 Skeletal Muscle –As the organ
• Skeletal muscles are
dominated by
 muscle tissue
 Also contain
 Nerve
 Blood vessels and
 Connective tissues.
They are surrounded by
dense irregular
connective tissue known
as the epimysium
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• Epimysium surrounds Skeletal Muscle –
several bundles known as
fascicles. the organ
• Each fascicle is a bundle of
super-long skeletal muscle
cells (muscle fibers),
surrounded by a layer of
dense irregular CT called
the perimysium
(peri=around).
• Each muscle cell extends
the length of the whole
muscle organ and is
surrounded by a fine layer
of loose connective tissue,
the endomysium.
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 Skeletal Muscle – Blood &
Nerve Supply
 Each skeletal muscle is supplied
by:
I. One nerve, forming motor unit
(the neuron innervating and the
muscle itself)
II. An artery and
[Link] or more veins.
 They all enter/exit via the
connective tissue coverings and
branch extensively.
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 Skeletal Muscle Attachments
• Muscles often are attached to bones at joints.
– They have two ends: origin (immovable end)
– Insertion end (movable end).

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 Direct attachments are less
Muscle attachments may common. The epimysium is
be direct or indirect. fused to a periosteum or a
perichondrium.

Indirect
attachments are
typical. The muscle
CT extends and
forms either a
cordlike structure (a
tendon) or a
sheetlike structure
(aponeurosis) which
attaches to the
periosteum or
perichondrium.
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 Skeletal Muscle Microanatomy

 Each skeletal muscle cell is known as a skeletal muscle

fiber because
• They are so long.
– Their diameter can be up to 100µm
– Their length can be as long as 30cm.
– They are so large because a single skeletal muscle cell
results from the fusion of hundreds of embryonic
precursor cells called myoblasts.
• A cell made from the fusion of many others is
known as a syncytium.
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Muscle fiber
PM is known
As sarcolemm
muscle fiber
cytoplasm is
known as
sarcoplasm

Sarcolemma has invaginations that penetrate through the cell called

transverse tubules or T tubules.

Sarcoplasm has lots of mitochondria (why?), lots of glycogen

granules (to provide glucose for energy needs) as well as myofibrils
and sarcoplasmic reticuli. 15
 Microanatomy
Sarcolemma.
 The sarcolemma is the cell membrane of the muscle fiber.

The sarcolemma consists of a true cell membrane, called the plasma

membrane, and an outer coat made up of a thin layer of polysaccharide
material that contains numerous thin collagen fibrils.

At each end of the muscle fiber, this surface layer of the sarcolemma
fuses with a tendon fiber, and the tendon fibers in turn collect into
bundles to form the muscle tendons that then insert into the bones.

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 Sarcoplasmic Reticulum-SR

• SR is muscle cell version of

the smooth endoplasmic
reticulum.
• Functions as a calcium
storage depot in muscle
cells.
• Well developed in the
skeletal muscle
• Loose network of this
membrane bound organelle
surrounds all the myofibrils
in a muscle fiber.
• We will see why this is so
important soon.
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Myofibrils →ACTIN and MYOSIN

 Each muscle fiber contains rod-like structures called myofibrils

extend the length of the muscle 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 filaments and thin
filaments.

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 Myofilaments
 2 types of myofilaments (thick & thin) make up myofibrils.
 Thick myofilaments are made up of the protein myosin
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
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• Each thin filament is made up of 3 different types of protein: actin,
tropomyosin, and troponin.
– Each thin filament consists of a long helical double strand.
– This strand is a polymer that resembles a string of beads.
– Each “bead” is the globular protein actin.
– On each actin subunit, there is a myosin binding site.
– Loosely wrapped around the actin helix and covering the myosin binding
site is the filamentous protein, tropomyosin.
– Bound to both the actin and the tropomyosin are proteins collectively
known as troponin (A, I, C).

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Note the relationship between the thin and thick filaments

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 Myofibrils
• Each myofibril is made up 1000 of repeating individual units
known as sarcomeres.
• Each sarcomere is an ordered arrangement of thick and thin
filaments.
• Notice that it has:
– Regions of thin filaments by themselves (pinkish fibers)
– Region of thick filaments by themselves (purple fibers)
– Regions of thick filaments and thin filaments overlapping.

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 Sarcomere
• The sarcomere is borderd by 2 protein structures
known as Z discs.
• The portion of the sarcomere which contains the thick
filament is known as the A band.
• A stands for anisotropic which is a fancy way of saying
that it appears dark under the microscope.
– The A band contains a zone of overlap (btwn thick & thin
filaments) and an H zone which contains only thick filaments

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 The portion of the
sarcomere which
does not contain any
thick filament is
known as the I band.

The I band contains only

thin filament and is
light under the
microscope (it is
isotropic).

One I band is actually

part of 2 sarcomeres
at once. In the middle of the H zone is a structure
called the M line which functions to hold
the thick filaments to one another
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 What Keeps the Myosin and Actin Filaments in Place?
 The side-by-side relationship between the myosin and actin filaments
is difficult to maintain.

 This is achieved by a large number of filamentous molecules of a

protein called titin.

 Each titin molecule has a molecular weight of about 3 million, which

makes it one of the largest protein molecules in the body.

 Also, because it is filamentous, it is very springy (Elastic).

 These springy titin molecules act as a framework that holds the

myosin and actin filaments in place so that the contractile machinery
of the sarcomere will work. 25
• Each muscle T-Tubules and the SR
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
sac (terminal Each T-tubule will be flanked by a terminal
cisterna). cisterna.
This forms a so-called triad consisting of 2
terminal cisternae and one T-tubule branch.
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27
Muscle Contraction: The Sliding Filament Hypothesis
• Place your right palm on the back
of your left hand.
• Now slide your right palm toward
your left elbow.
– What happened to the
distance between your
elbows?
• It got shorter!
– This is how muscle
contraction occurs.
– 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 on
the endomysium,
perimysium, epimysium and
attached tendon and then
pulls on the bone. 28
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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30
 Sliding Filaments
• All the sarcomeres in a fiber will contract together.
This contracts the fiber itself.
• The number of fibers contracting will determine the
force of the contraction of the whole muscle.
• The whole process of muscle contraction can be
divided into 4 steps:
– Excitation
– Excitation-contraction coupling
– Contraction
– Relaxation

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 Excitation
• All cells have a voltage difference across their plasma
membrane. This is the result of several things:
1. The ECF is very high in Na+ while the ICF is very high in K+.
The PM is impermeable to Na+ but slightly permeable to
K+. As a result, K+ is constantly leaking out of the cell. In
other words, positive charge is constantly leaking out of
the cell.

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 Excitation

2. The Na+/K+ pump is constantly pumping 3 Na+ ions out and

2 K+ ions in for every ATP used. Thus more positive charge
is leaving than entering.
3. There are protein anions (i.e., negatively charged proteins)
within the ICF that cannot travel through the PM.

• What this adds up to is the fact that the inside of the

cell is negative with respect to the outside. The
interior has less positive charge than the exterior. 33
 Excitation
• This charge separation is known as a membrane
potential (MP).
• The value for MP in inactive muscle cells is typically
btwn –80 and –90 millivolts.
• Cells that exhibit a MP are said to be polarized.
• MP can be changed by influx or efflux of
charge.

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 Excitation
• The PM has integral proteins that act as gated ion channels.
These are channels that are normally closed, but in response
to a certain signal, they will open and allow specific ions to
pass through them.
• Ion channels may be:
– Ligand-gated  the binding of an extracellular molecule (e.g.,
hormone, neurotransmitter) causes these channels to open.
– Voltage-gated   MP causes these channels to open.
– Mechanically-gated  stretch or mechanical pressure opens these
channels.
• When a channel is open, its specific ion(s) will enter or exit
depending on their electrochemical gradient.

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 Excitation
• In general each muscle is
served by one nerve – a bundle
of axons carrying signals from
the spinal cord to the muscle.
• W/i 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 btwn a neuron and any other cell is

known as a synapse. The synapse btwn a neuron and a
muscle is known as the neuromuscular junction.
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 Excitation
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 with
vesicles that
contain the
neurotransmitter,
acetylcholine.
The motor end
plate is chock full
of acetylcholine
receptors.
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 Excitation
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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 Excitation
• Adjacent to the motor end plate, the sarcolemma
contains voltage-gated ion channels.
• In order for these channels to open, the MP must
depolarize from its resting value of –90mV to
approximately –50mV.

• This is the threshold. MP must become this much

positive for the voltage-gated channels to open.

• The degree of depolarization depends on how much

Na+ influx occurred which in turn depends on how
many Na+ channels were opened by binding Ach
leading to the generation of end plate potential (EPP)
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 Excitation
• If the MP fails to depolarize to threshold,
nothing will happen.

• The MP will soon return to normal and no

muscle contraction will occur.
• If the MP does reach threshold, 2 types of
voltage-gated ion channels will open:
– Fast Na+ channels
– Slow K+ channels
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• If MP reaches threshold, fast Na+ channels open and Na+ rushes in
causing the MP to depolarize to +30mV.

• The depolarization stops when the Na+ channels become

inactivated.

• At this point, slow K+ channels shall open & K+ efflux occurs.

• This returns MP back to its resting level. This is repolarization.

• If we were to graph this change in MP over time, it would look

somewhat like the animation below.

• This is known as an action potential.

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 Excitation-Contraction Coupling

It is a mechanism by which an action potential spreads in to the skeletal muscle.

The AP travels along the sarcolemma going in both directions away from the motor end plate.

Since T-tubules are simply invaginations of the sarcolemma, the AP will spread down and
through them as well. This is really important!

42
 Excitation-Contraction Coupling
• The T-tubular sarcolemma contains voltage sensitive proteins that
change their conformation in response to a significant Vm.
– These are physically linked to calcium channels in the SR membrane
– Upon Vm, the voltage sensors change their conformation. This
mechanically opens the Ca2+ channels in the SR membrane.

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Excitation-Contraction Coupling
The SR Ca2+ channels are only open briefly, but a large Ca2+ gradient
exists so a large amount of calcium enters the sarcoplasm.

The Ca2+
interacts with the
2 regulatory
proteins of the
sarcomere so that
the 2 contractile
proteins can slide
& the sarcomere
can shorten.

44
 Let’s backtrack for just a moment…

• Now that we know what an action potential is,

it should be noted that the exocytosis of the
ACh vesicles is caused by the arrival of an AP
at the synaptic end bulb.
• The AP causes the opening of voltage-gated
Ca2+ channels in the synaptic end bulb plasma
membrane. The resulting calcium influx
causes the exocytosis of the vesicles.

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• Normally, tropomyosin
obstructs the myosin binding
site on the G-actin subunits.
Contraction
• Calcium binds to the troponin-
C polypeptide of the troponin
triad.

• This changes the conformation

of troponin which changes the
conformation of tropomyosin
which exposes the myosin
binding site on actin.

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 Contraction
• Once actin’s myosin binding site is exposed, myosin will attach to it.
– At this point myosin has just hydrolyzed ATP into ADP and P i –
however both molecules are still bound to the myosin.
– The ATP hydrolysis provides the energy for the “cocking” of the
myosin head
• Once myosin is bound to actin, the myosin head will release the
ADP and Pi which will cause it change conformation.
• This results in the thin filament sliding along the thick filament.
• Myosin then remains bound to actin until it binds to another ATP.
• Myosin then hydrolyzes the new ATP and the cycle can begin again.

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 Contraction Strength
• Strength of is a function of:
1. The number of crossbridges that can be made
per myofibril
2. The number of myofibrils per muscle fiber
3. The number of contracting muscle fibers

48
 Mechanism of muscle contraction
Summary
(Excitation-contraction coupling)
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 follows:
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 nicotinic receptors 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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 Mechanism of muscle contraction
(Excitation-contraction coupling
7. Depolarization of T-tubules stimulate SR to release Ca 2+ 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 is 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 movement 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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 Relaxation
• Calcium pumps in the SR membrane work
constantly to get the calcium out of the
sarcoplasm and back into the SR. Ca2+ -
pump

• They are unable to do this as long as the

muscle is still binding ACh.

• ACh is released by the motor neuron as long as

it keeps being stimulated.
• Note that ACh does not remain bound to the
AChR for very long.
• It quickly releases and either binds again or
more likely is hydrolyzed by the enzyme
acetylcholinesterase which exists as part of the
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sarcolemma and free within the synaptic cleft
Relaxation
• When the muscle ceases
being stimulated, the
calcium pumps “win” and
sarcoplasmic [Ca2+] drops.
– Calcium stops being
available for troponin
and tropomyosin shifts
back into its inhibitory
position.
• The muscle then returns
back to its original length
via the elasticity of the This animation shows
connective tissue another way to induce
elements, plus the muscle relaxation.
contraction of antagonistic
muscles, and gravity. 52
 Mechanism of muscle relaxation
It has the following steps
1. Following muscle contraction, Ca2+ is re-up-taken 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. To remove the head of myosin from actin
53
Drugs Acting in the Neuromuscular Junction
Some drugs facilitate synaptic trans mission in NMJ.
These include:
Pilocarpin
carbachol
Some drugs potentiate the effect of acetylcholine in NMJ.
These include:
Neostigmine
Physiostigmine
Some drugs block NMJ.
These include
Detubo curarie

54
 Rigor Mortis
• Upon death, muscle cells are unable to prevent
calcium entry.

• This allows myosin to bind to actin.

• Since there is no ATP made postmortem, the myosin

cannot unbind and the body remains in a state of
muscular rigidity for almost the next couple of days.

55
 Muscle Metabolism
• The chemical energy released by the hydrolysis of ATP is
necessary for both muscle contraction and muscle
relaxation.

• Muscles typically store limited amounts of ATP – enough to

power 4-6s of activity.
– So resting muscles must have energy stored in other
ways.

56
 Resting Muscle and
the Krebs Cycle
• Resting muscle fibers typically takes up
fatty acids from the blood stream.
– How might they enter the cell?
– Inside the muscle fiber, the FA’s are oxidized to several
molecules of a compound called Acetyl-CoA. This oxidation
will also produce several molecules of NADH and FADH2.
– Acetyl-CoA will then enter a cyclical series of reactions known
as the Krebs cycle or Tricarboxylic Acid cycle.
– In the Krebs cycle, acetyl-CoA combines with the compound
oxaloacetate and then enters a series of reactions.
– The end products of these reactions are: CO2, ATP, NADH,
FADH2, and oxaloacetate (thus we call it a cycle) 57
Krebs Cycle Products

Oxaloacetate will simply combine

with another molecule of acetyl-
CoA and reenter the cycle.

NADH and FADH will enter another series of reactions known as the
Electron Transport Chain.
These reactions occur along the inner membrane of the mitochondrion
and they basically consist of the passing of electrons from compound to
another compound with energy being released each time and used to
drive the synthesis of ATP.
The final electron acceptor is oxygen when it combines with 2
hydrogen atoms to yield water. 58
 Krebs Cycle Products

• CO2 will diffuse out of the mitochondria, out of

the muscle fiber, and into to the blood stream
which will take it to the lungs for expiration.

• The ATP made in the Krebs cycle plus the ATP

made during the ETC will be used in many ways.

59
 ATP Use in the Resting Muscle Cell
• ATP is necessary for cellular housekeeping duties.

• ATP powers the combination of glucose monomers (which

have been taken up from the blood stream) into the
storage polymer glycogen.

• ATP is used to create another energy storage compound

called creatine phosphate or phosphocreatine:
ATP +

60
 Working Muscle
• As we begin exercising, we almost immediately use our
stored ATP.
• For the next 15 seconds or so, we turn to the
phosphagen system, the energy stored in creatine-
phosphate.
Creatine-P + ADP Creatine Kinase Creatine + ATP
– The ATP is then available to power contraction and
relaxation: myosin ATPase, Ca2+ ATPase in the SR
membrane, and Na+/K+ ATPase in the sarcolemma.
– The phosphagen system dominates in events such as
the 100m dash or lifting weights.

61
62
 Working Muscle
• After the phosphagen system is depleted, the muscles
must find another ATP source.

• The process of anaerobic metabolism can maintain ATP

supply for about 45-60s.

• Anaerobic means “without air,” and it is the breakdown

of glucose without the presence of oxygen.
– It usually takes a little time for the respiratory and
cardiovascular systems to catch up with the muscles
and supply O2 for aerobic metabolism.
63
 Anaerobic Metabolism
• Glucose is supplied by the breakdown of glycogen or via uptake
from the bloodstream.

• Glucose is broken down into 2 molecules of pyruvic acid, with

the concomitant of 2 ATP generation and the conversion of 2
molecules of NAD+ into NADH.

• This process is known as glycolysis and it occurs in the

sarcoplasm.
– Unfortunately, without O2, we cannot use the NADH in the
ETC.
– In order for more glycolysis to proceed, the muscle cell must
regenerate the NAD+.
– It does this by coupling the conversion of pyruvic acid into
lactic acid with the conversion of NADH into NAD+ 64
Anaerobic Metabolism
• Lactic acid typically diffuses out of
muscles into the blood stream and is
taken to the liver, kidneys, or heart
which can use it as an energy source.

• Anaerobic metabolism is inefficient.

• Large amounts of glucose are used
for very small ATP returns.

• Plus, lactic acid is a toxic end product

whose presence contributes to
muscle fatigue.

• Anaerobic metabolism dominates in

sports that requires bursts of speed
and activity, e.g., basketball. 65
 Aerobic Metabolism
• Occurs when the respiratory and cardiovascular
systems have “caught up with” the working muscles.
– Prior to this, some aerobic respiration will occur
thanks to the muscle protein, myoglobin, which
binds and stores oxygen.

• During rest and light to moderate exercise, aerobic

metabolism contributes 95% of the necessary ATP.

• Substrates which can be aerobically metabolized

include:
– Pyruvic acid (made via glycolysis), fatty acids, and
66
amino acids.
 Aerobic
Metabolism
• It occurs in the
mitochondria.
• Pyruvic acid from glycolysis
is the primary substrate.
The cell also utilizes fatty
acids and amino acids.
• Aerobic respiration typically
yields 36 ATP per molecule
of glucose. Compare this to
anaerobic metabolism.

67
 Muscle Fatigue

• Physiological inability to contract

• Results primarily from a relative deficit of
ATP.
• Other contributing factors include the
decrease in sarcoplasmic pH, increased
sarcoplasmic [ADP], and ionic imbalances.

68
 Oxygen debts
• Refers to the fact that post-exercise breathing rate is much
much greater than resting breathing rate

• This excess oxygen intake serves many tasks:

– Replenish the oxygen stored by myoglobin and hemoglobin

– Convert remaining lactic acid back into glucose
– Used for aerobic metabolism to make ATP which is used to:
• Replenish the phosphagen system
• Replenish the glycogen stores
• Power the Na+/K+ pump so as to maintain RMP
69
 Whole Muscle Contraction

• A sub-threshold stimulus would not cause

contraction because no AP would be produced!
• The response of a muscle to a single supra-
threshold stimulus would be a twitch – the
muscle quickly contracts and then relaxes.
• Let’s take a look at a measurement of a
neuron’s AP, a muscle fiber’s AP, and the
tension developed by that muscle fiber.

70
71
 Phases of the Muscle Twitch
1. Latent Period
– Time between stimulus and generation of tension
– Includes all time required for excitation,
excitation-contraction coupling, and stretching of
the series of elastic components.
2. Contraction
3. Relaxation

Now, let’s look at various types of muscle twitches

72
Here we have multiple twitches separated by ample time.
Notice that the previous twitch has no effect on a new twitch
and that these twitches are similar in size. This is why we can
say that muscle contraction – at least on the level of a single
fiber – is an all-or-none event.

The black arrows signify stimulation

73
Here, we have an initial stimulation and resulting twitch all by itself.
Then we have 2 stimuli in somewhat rapid succession. The 2nd twitch
has added on to the first.
This is known as wave or temporal summation.

It occurs because there is still calcium from the 1st twitch in the
sarcoplasm at the time of the 2nd twitch.

74
Here, we have wave summation
until max tension is achieved.
Maximum tension is known as
tetanus.

Do not confuse this with the disease

caused by the bacterium
Clostridium tetani.
Its toxins prevent the normal
inhibition of muscle contractions as
mediated in the spinal cord.

This leads to uncontrolled, Btwn stimulations, only the tiniest

unwanted muscle contraction and bit of relaxation occurs. Since some
ultimately respiratory arrest. relaxation does occur, we say the
tetanus is unfused or incomplete.
Most muscle actions occur as a
result of muscle fibers undergoing
asynchronous, unfused tetanus
75
Here, the stimuli are close enough to one another so that
tetanus is complete and no relaxation occurs until fatigue
sets in.

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Here we have the phenomenon known as treppe (German
for staircase). Notice that the subsequent contractions
grow stronger. There 2 reasons for this:
1. Slight increase in sarcoplasmic [Ca2+]
2. Heat liberated by working muscle increases the
rate and efficiency of enzyme function within the muscle
fiber.

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• A motor unit is defined as a somatic Motor Units
motor neuron and all the skeletal
muscle fibers it innervates.
• When this neuron is stimulated, all
the muscle fibers it synapses upon
will be stimulated and will contract
as a unit
• The # 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 Notice that the muscle fibers of
large postural muscles have large a single unit are not clustered
motor units together but are spread out.
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Types of Skeletal Muscle Contractions

Contractions can be:

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

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 Isotonic Contraction
• Tension reaches a plateau and then the muscle shortens.
Consider the following experiment:
1. A skeletal muscle 1cm2 in cross-sectional area can develop
roughly 4kg of force in complete tetanus.
2. If we hang a 3kg weight from that muscle and stimulate it, the
muscle will shorten.
3. Before the muscle can shorten, the cross-bridges must produce
enough tension to overcome the resistance – in this case the 3kg
weight. Over this period, internal tension in the muscle fibers
rises until the external tension in the tendon exceeds the amount
of resistance.
4. As the muscle shortens, the internal and external tensions in the
muscle remain constant at a value that just exceeds the
resistance.

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81
 Resistance and Speed of Contraction
• There is an inverse relationship
between the amount of
resistance and the speed of
contraction.
• The heavier the load, the longer
it takes for the movement to
begin because muscle tension,
which increases gradually, must
exceed the resistance before
shortening can occur
– More cross-bridges must be
formed, more fibers involved. This
takes more time.

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 Isometric Contractions
• The muscle as a whole does not change length and
the tension produced never exceeds the
resistance.
• Consider the following:
– To the same muscle as before, we attach a 6kg weight.
– Although cross-bridges form and tension rises to peak
values, the muscle cannot overcome the resistance of
the weight and cannot shorten.
– Although the muscle as a whole does not shorten, the
individual fibers shorten until the tendons are taut and
the external tension equals the internal tension. The
muscle fibers cannot shorten further because the
external tension does not exceed the resistance.
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84
 Muscle Tone
• Some of the motor units with in particular muscle are
always active, even when the muscle is not
contracting.
– Their contractions do not produce enough tension to cause
movement, but they do tense and firm the muscle.
– This resting tension in a skeletal muscle is called tone.
– The identity of the motor units involved changes
constantly.

• Resting muscle tone stabilizes the position of bones

and joints.

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Muscle Fiber Types

2 main types:
1. Slow fibers
2. Fast fibers

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 Slow Fibers

• Contract slowly because its myosin ATPases

work slowly.
• Depends on oxygen delivery and aerobic
metabolism.
• Is fatigue resistant and has high endurance.
• Is thin in diameter – large amount of cytoplasm
impedes O2 and nutrient diffusion.

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 Slow Fibers Cont’d…
• Cannot develop high tension – small diameter
means few myofibrils.
• Has rich capillary supply and lots of mitochondria.
• Contains lots of the O2-storing protein, myoglobin
which gives it a red color.
• Uses lipids, CHO, and amino acids as substrates for
its aerobic metabolism.
• Best suited for endurance type activities.
• Red fibers, slow oxidative fibers, type I fibers.

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 Fast Fibers
• So named because they can contract in 0.01
seconds or less after stimulation.
• Fast fibers are large in diameter; they contain
densely packed myofibrils, large glycogen
reserves, and relatively few mitochondria.
• Able to develop a great deal of tension b/c they contain a large
number of sarcomeres.
• Use ATP in massive amounts. Supported by anaerobic
metabolism. Fatigue rapidly.
• fast fatigue (FF) fibers, fast glycolytic (FG) fibers, white fibers.
• Best suited for short term, power activities.

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 Muscular Dystrophy
• Group of inherited muscle-destroying
diseases that generally appear during
childhood.
• Dys=faulty; Troph=growth
• Most common is Duchenne muscular
dystrophy
– DMD is caused by an abnormal X-linked
recessive gene
– Diseased muscle fibers lack the protein
trophin which normally links the
cytoskeleton to the ECM and stabilizes
the sarcolemma
– Age of onset is btwn 2 and 10. Muscle Here is a slide of skeletal
weakness progresses. Afflicted
individuals usually die of respiratory
muscle from someone with
failure, usually by age 25. DMD. Look how much
connective tissue there is.
Lots of adipose tissue too.
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 Other Important Terms
• Flaccid paralysis
– Weakness or loss of muscle tone typically due to injury or
disease of motor neurons. E.g., LMNL
• Spastic paralysis
– Sustained involuntary contraction of muscle(s) with
associated loss of function. E.g., UMNL

• Spasm
– A sudden, involuntary smooth or skeletal muscle twitch.
Can be painful. Often caused by chemical imbalances.

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 Other Important Terms

• Cramp
– A prolonged spasm that causes the muscle to
become taut and painful.
• Hypertrophy
– Increase in size of a cell, tissue or an organ.
• In muscles, hypertrophy of the organ is always due to
cellular hypertrophy (increase in cell size) rather than
cellular hyperplasia (increase in cell number)
• Muscle hypertrophy occurs due to the synthesis of more
myofibrils and synthesis of larger myofibrils.

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 Other Important Terms

• Atrophy
– Reduction in size of a cell, tissue, or organ
• In muscles, its often caused by disuse. Could a nerve
injury result in disuse? Why might astronauts suffer
muscle atrophy?
• Fibrosis
– Replacement of normal tissue with heavy fibrous
connective tissue (scar tissue). How would fibrosis
of skeletal muscles affect muscular strength? How
would it affect muscle flexibility?

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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. 94
 Smooth Muscle

• Integumentary system:
– Regulates blood flow to the superficial dermis
– Allows for piloerection
• Respiratory system
– Alters the diameter of the airways and changes the
resistance to airflow
• Urinary system
– Sphincters regulate the passage of urine
– Smooth muscle contractions move urine into and out of
the urinary bladder

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 Smooth Muscle
• Reproductive system
– Females
• Assists in the movement of the egg (and of sperm)
through the female reproductive tract
• Plays a large role in childbirth
– Males
• Allows for movement of sperm along the male
reproductive tract.
• Allows for secretion of the non-cellular components of
semen
• Allows for erection and ejaculation

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 Smooth Muscle
• 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. Nor perimysium or
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
• Smooth muscle is always maintaining a normal
level of activity – creating muscle tone.
• Smooth muscle can respond to stimuli by altering
this tone in either direction.
– Smooth muscle can be inhibited and relax
– Smooth muscle can be excited and contract
• Possible stimuli include neurotransmitters,
hormones, pH, Pco2, Po2, metabolites (such
as lactic acid, ADP), or even stretch.

99
 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.

100
 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.

101
Smooth muscle relaxation:

Calcium is pumped out of the cell,

which decreases the amount of active
calmodulin which decreases the
amount of active MLCK which
decreases the number of crossbridges.

MLC phosphatase is required (removes

phosphate from the myosin)

Relaxation can occur subsequent to

contraction or at any time if anything
causes a decrease in the calcium
permeability of the smooth muscle cell.

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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, arrector
pili, 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
joined by structures called Notice the branching
intercalated discs – which and the intercalated
consist of desmosomes and disc, indicated by the
gap junctions. blue arrow.
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