UNIT 8: MUSCLES

BIOL2410 D01 Lecture Notes

 (c) Smooth muscle

I) Smooth Muscle: Structure Muscle fiber

Ø General Characteristics of Smooth Muscle Cells: Nucleus

1. Small spindle shaped, uninucleate (one nucleus) cells
Fig. 12.1
2. Not striated – proteins are not organized into
sarcomeres.
Fig. 12.1
3. Cells are organized into sheets or tubes that allow
for simultaneous contraction
Ø Often the sheets/tubes are organized into layers of
smooth muscle that are oriented in multiple directions.
For example the stomach has circular, longitudinal and
oblique layers of smooth muscle.

Fig. 21.1
https://nursing.unboundmedicine.com/nursingce
ntral/view/Tabers-Dictionary/765922/all/stomach
 (c) Smooth muscle

I) Smooth Muscle: Structure Muscle fiber

Ø General Characteristics of Smooth Muscle Cells: Nucleus

1. Small spindle shaped, uninucleate (one nucleus) cells
Fig. 12.1
2. Not striated – proteins are not organized into Fig. 12.1
sarcomeres.
3. Cells are organized into sheets or tubes that allow
for simultaneous contraction
Ø Often the sheets/tubes are organized into layers of
smooth muscle that are oriented in multiple directions.
For example the stomach has circular, longitudinal and
oblique layers of smooth muscle.
4. Have few similarities to skeletal and cardiac muscle
cells including that:
Ø they contain thick and thin myofilaments (myosin and
actin) that will form crossbridges, but they are organized
differently.
Ø increasing Ca++ in the cytosol is required to initiate Fig. 12.25
contraction.
 (c) Smooth muscle

I) Smooth Muscle: Structure Muscle fiber

Ø General Characteristics of Smooth Muscle Cells: Nucleus

5. Have many differences from other muscle types and
can be highly variable since: Fig. 12.1
Fig. 12.1
a) They must operate over a range of lengths. Since
smooth muscle is not attached to bone, it is not subject
to the same limitations on stretch as skeletal muscles.
Ø E.g.1: detrusor muscle that forms the bladder wall stretches
out when filled with urine and returns to shorter length
when empty.
Ø E.g.2: Smooth muscle of the wall of the uterus during
pregnancy becomes extremely stretched out, but still needs
to be able to produce powerful contractions for childbirth.
b) They contract and relax more slowly
Ø Use GPCRs instead of chemically (ligand) gated ion
channels – using a second messenger system takes more
time

Fig. 12.24
I) Smooth Muscle: Structure
Ø General Characteristics of Smooth Muscle Cells:
5. Have many differences from other muscle types and
can be highly variable since:
c) They use less energy for contraction than skeletal or
cardiac muscle
Ø Smooth muscle cells have the ability to slow down their
myosin ATPase so that crossbridges form more slowly and
less ATP will be used.
d) They can sustain contractions for extended periods of
time (termed the “latch” state mechanism).
Ø Allows muscle to maintain high tension at low energy
consumption (prevents fatiguing)
Ø During latch state myosin head is stuck (latched to actin).
I) Smooth Muscle: Structure
Ø Individual Cell Structure:
1. Contains thick and thin myofilaments, but they are not arranged
into sarcomeres and myofibrils.
Ø Actin is more plentiful and attached to structures called dense
bodies (similar function as Z-disks in cardiac and skeletal muscle).
Dense bodies are spread throughout the cell and attached to the
cell membrane.
Ø Thin filaments lack troponin – Ca++ still helps to regulate
contraction, but the mechanism is different
Ø Less myosin
Ø Myosin filaments are longer
Ø Entire surface of thick filament is covered with myosin heads (compared
to skeletal and cardiac muscle where the myosin heads are found
toward each end of the thick myofilament)
2. Extensive cytoskeleton
Ø Many intermediate filaments that interconnect the dense bodies
(some of which are connected to the cell membrane). Fig. 12.25
I) Smooth Muscle: Structure
Ø Individual Cell Structure:
4. Amount of sarcoplasmic reticulum varies and is less abundant and less
organized than in skeletal or cardiac muscle.
Ø Similar to skeletal and cardiac muscle, the SR accumulates and releases Ca++.
5. No T-tubules, but have caveolae
Ø Caveolae = small invaginations/pits in cell membrane. Unlike T-tubules they
do not pass very deeply into the cell. Like little caves on the cell surface.
Ø Are lipid rafts in the cell membrane made up of sphingolipids and cholesterol.
They are the location of several different types of receptors for different
signaling molecules involved in controlling smooth muscle. For example:
a) receptors for hormones like serotonin.
b) adrenergic receptors for epinephrine/norepinephrine (both the
neurotransmitter and hormone forms).
c) muscarinic receptors for acetylcholine. Hall, J.E. 2020. Guyton and Hall Textbook of Medical Physiology,
13th edition. Elsevier, Canada.
d) Receptors for nitric oxide, endothelins.
e) G-protein receptors.
f) L-type calcium channel (DHP) receptors.
J) Smooth Muscle: Physiology
Ø Functional Classification of Smooth Muscle:
1. By location:
Ø Smooth muscle is named for the organ or organ
system that it forms (gives a general idea of the function):
Ø E.g. Vascular smooth muscle; gastrointestinal smooth
muscle; urinary; respiratory (bronchial, bronchiolar);
reproductive; ocular, etc.
2. By contraction pattern:
a) Phasic smooth muscles – alternate between contraction and
relaxation. Muscle is
Ø Normally relaxed and contracts only when signaled (esophagus, urinary
bladder, etc). OR
Ø Cycles at regular intervals between contraction and relaxation (stomach
intestines)
b) Tonic smooth muscles – are continuously contracted. Muscle is:
Ø Normally contracted and relaxes only when signaled (sphincters), OR
Ø Level of contraction is varied in response to body needs (blood vessels,
airways) similar to Figure 12.22
J) Smooth Muscle: Physiology
Ø Functional Classification of Smooth Muscle:
3. By communication with neighboring cells:
a) Single unit smooth muscle (visceral smooth muscle)
Ø form large sheets
Ø have many gap junctions (allows ion movements between cells)
Ø functions like one cell (syncytia) – coordinated contraction
Ø ANS neuron stimulate only some cells (varicosities end near peripheral
cells) and those relay the signal to other cells through gap junctions.
Ø found in walls of hollow organs (stomach, intestine, urinary bladder, etc).
b) Multi-unit smooth muscle
Ø lack gap junctions (cells act individually)
Ø ANS neuron innervates all individual cells (varicosities are embedded in
between cells)
Ø found in areas where fine graded contractions are needed to produce
fine movements (ciliary muscles of the eye – control the shape of the
lens for focusing; arrector pili muscles in the skin)
Fig. 12.23
J) Smooth Muscle: Physiology
Ø Contraction & Relaxation Overview:
1. Contraction is initiated by electrical signals or chemical signals or both.
Ø Contraction can be regulated by:
a) The autonomic nervous system (sympathetic and parasympathetic)
Ø Smooth muscle cells lack a specialized receptor region (i.e. there is no
motor endplate like in skeletal muscle).
b) Hormones including:
Ø epinephrine and norepinephrine,
Ø Also hormones that influence the operation of smooth muscle in
specific organs/organ systems
Ø e.g.1: the action of oxytocin on the smooth muscle of the uterus during
labour
Ø e.g.2: the action of gastrointestinal hormones on contraction and emptying
of the stomach
c) Autocrines/Paracrines like histamine, nitric oxide, etc.
d) Local factors such as CO2 levels, oxygen levels, pH, temperature, etc.
e) Stretch of the smooth muscle (myogenic response). Fig. 12.29
J) Smooth Muscle: Physiology
Ø Contraction & Relaxation Overview:
2. Electrical or Chemical signal causes an increase in cytosolic Ca++
concentration.
Ø Ca++ for contraction comes from BOTH the extracellular fluid AND the
sarcoplasmic reticulum (unlike skeletal muscle where it is just from the SR, but
similar to cardiac muscle).
3. Increasing Ca++ concentration in the cytosol initiates a cascade of events
that leads to phosphorylation of a small protein on myosin called the
myosin light chain (MLC). Phosphorylation of MLC by a kinase (enzyme)
called myosin light chain kinase (MLCK) activates the myosin ATPase. Myosin Light
4. Activation of myosin ATPase allows for crossbridges to form between Chain (MLC)
actin and myosin, and the pivoting of the myosin head, which results in
contraction.
5. Relaxation of the smooth muscle cell is caused by deactivation of the
myosin ATPase, which involves dephosphorylation of the myosin light
After Quintin, S., Gally, C., and Labouesse, M. 2008.
chain by the enzyme myosin light chain phosphatase (MLCP). Epithelial morphogenesis in embryos: asymmetries,
motors and brakes. Trends in Genetics 24: 221-230.
J) Smooth Muscle: Physiology Know this diagram!!

Ø Smooth Muscle Contraction Details:

Ø Steps:
1. Depolarization of membrane to threshold (~-35mV) or signaling by
hormone/neurotransmitter or stretch of the smooth muscle cell that
either:
a) triggers DHP (dihydropyridine) voltage gated calcium channels (also
known as L-type channels) in the calveolae to open –OR–
b) Triggers ligand gated Ca++ channels to open
c) Triggers receptor operated calcium channels (ROCCs) to open
(these are calcium channels in the membrane that open in response
to activation of a GPCR).
d) activates a GPCR-Phospholipase C pathway that results in
production of IP3 (inositol triphosphate) and DAG (diacylglycerol).
2. Release of calcium from the sarcoplasmic reticulum (SR) by either:
a) calcium from 1a/1b/1c binding to the ryanodine receptor calcium
release channel on the SR (calcium induced calcium release) –OR–
b) IP3 from 1b binding to the IP3 receptor on the SR. Fig. 12.26a
J) Smooth Muscle: Physiology Know this diagram!!

Ø Smooth Muscle Contraction Details:

Ø Steps:
3. High concentrations of cytosolic Ca++ promote the binding of Ca++
to a cytosolic protein called calmodulin (CaM).
4. Ca++-calmodulin complex activates the enzyme myosin light chain
kinase (MLCK).
5. MLCK phosphorylates the myosin light chain.
6. Myosin ATPase activity increases (ATP is broken down into ADP and
inorganic phosphate, Pi)
7. Myosin binds to actin (crossbridge formation)
8. Crossbridge cycling (repeated binding and power stroke of myosin
that pulls actin) results in contraction and an increase in muscle
tension.

Fig. 12.26a
J) Smooth Muscle: Physiology
Ø Smooth Muscle Contraction Details:

Fig. 12.26a
 Know this
J) Smooth Muscle: Physiology diagram!!

Ø Smooth Muscle Relaxation Details:

Ø Steps:
1. Depolarization/Chemical Signaling/Stretch end.
2. Ca++ is pumped out of the cytosol
a) back into the sarcoplasmic reticulum by Ca++ ATPase pumps in the SR
membrane.
b) back into the ECF/ISF (extracellular fluid/interstitial fluid) by sodium calcium
exchangers (NCX) in the cell membrane
3. Decreasing the concentration of Ca++ in the cytosol causes Ca++ to
unbind from calmodulin.
4. Without the Ca++-calmodulin complex, myosin light chain kinase (MLCK)
activity decreases.
5. Myosin light chain phosphatase (MLCP) activity increases relative to the
decrease in MLCK activity.
6. MLCP dephosphorylates myosin ATPase, reducing its activity.
7. Less myosin ATPase activity, means fewer crossbridges form and the
muscle relaxes (less crossbridges = less tension).
Fig. 12.26b
 Know this
J) Smooth Muscle: Physiology diagram!!

Ø Smooth Muscle Relaxation Details:

Ø Steps:
1. Depolarization/Chemical Signaling/Stretch end.
2. Ca++ is pumped out of the cytosol
a) back into the sarcoplasmic reticulum by Ca++ ATPase pumps in the SR
membrane.
b) back into the ECF/ISF (extracellular fluid/interstitial fluid) by sodium calcium
exchangers (NCX) in the cell membrane
3. Decreasing the concentration of Ca++ in the cytosol causes Ca++ to
unbind from calmodulin.
4. Without the Ca++-calmodulin complex, myosin light chain kinase (MLCK)
activity decreases.
5. Myosin light chain phosphatase (MLCP) activity increases relative to the
decrease in MLCK activity and becomes dominant.
6. MLCP dephosphorylates myosin ATPase, reducing its activity.
7. Less myosin ATPase activity, means fewer crossbridges form and the
muscle relaxes (less crossbridges = less tension).
Fig. 12.26b
J) Smooth Muscle: Physiology
Ø Smooth Muscle Relaxation Details:
Ø Phosphate-Mediated Ca++ Sensitivity:
Ø Changes in phosphatase activity change how myosin
responds to different levels of Ca++
Ø MLCP (myosin light chain phosphatase) activity decreases High relative MLCK
activity (= higher Low relative MLCK
the ability of smooth muscle to generate tension, therefore phosphorylation) activity (= higher
MLCP activity relaxes smooth muscle. dephosphorylation)

Ø Inhibition of MLCP (which inhibits dephosphorylation of

MLC) causes sensitization of the myosin
Ø a lot of force is produced even at lower calcium levels than
normal.
Ø occurs because there is high MLCK activity relative to MLCP
activity (phosphorylation is dominant) .
Ø High MLCP (phosphatase) activity desensitizes myosin Fig. 12.27
Ø higher levels of cytosolic calcium compared to normal are
needed to produce the same level of force.
Ø occurs because there is low MLCK activity relative to MLCP
activity (dephosphorylation is dominant).
J) Smooth Muscle: Physiology
Ø How does calcium enter the cell and how
is it then released from the SR?:
1. Calcium moves into the into the cell in response to:
a) depolarization that opens voltage-gated Ca2+ channels
b) binding of neurotransmitters, hormones, etc. that open ligand
gated Ca2+ channels or receptor-operated Ca2+ channels (ROCC)
c) stretch of smooth muscle that opens stretch activated calcium
channels
Ø open when pressure or other force distorts membrane
Ø the contraction of smooth muscle in response to stretch is
known as myogenic contraction
Ø common in arterioles that regulate blood pressure
Ø For example, when you stand up, the blood pressure in the
arterioles in your feet increases due to gravity. In response,
the arterioles undergo myogenic contraction to reduce blood
flow to the feet, which helps to reduce pressure.
Fig. 12.29
J) Smooth Muscle: Physiology
Ø How does calcium enter the cell and how
is it then released from the SR?:
2. Calcium release from the SR due to:
a) cytosolic calcium that entered from the ECF
binding to Ryanodine receptor (RyR) calcium
release channel on sarcoplasmic reticulum
(SR)
b) GPCR activation à activates phospholipase C
à produces second messenger = IP3 à
binds to and opens an IP3-receptor channel
on SR
c) When SR Ca2+ stores get low à triggers
opening of Store-operated Ca2+ channels
(SOCCs) in the cell membrane (more Ca++
can enter into cytosol).

Fig. 12.29
J) Smooth Muscle: Physiology
Ø Smooth Muscle Regulation:
1. Many smooth muscles are controlled by both sympathetic and
parasympathetic neurons
2. Hormones and paracrines/autocrines also control smooth muscle.
Examples:
a) Histamine constricts smooth muscles of the airways
Marieb and Hoehn 2019
Ø Allergens in the airways cause some white blood cells to release histamine which
activates a GPCR-Pchospholipase C pathway in bronchiolar cells, resulting in creation
of IP3 (IP3 causes release of Ca++ from the SR).
Ø Histamine causes contraction of the smooth muscle in the airway
(bronchoconstriction).
b) Nitric oxide relaxes smooth muscle of blood vessels
Ø Acts on a GPCR that results in activation of a protein kinase that prevents an increase
in cytosolic calcium (no Ca++ = relaxation)
Ø For example - sexual arousal to increase blood flow in the penis/clitoris.
Ø One of the roles of erectile dysfunction medications like Viagra and Cialis is to
increase nitric oxide production, which causes relaxation and dilation of the blood
vessels in the penis (there is some evidence it does the same for the clitoris). Fig. 12.29
J) Smooth Muscle: Physiology
Ø Excitation Contraction Coupling in Smooth Muscle:
Ø 2 mechanisms:
1. Electromechanical coupling
Slow wave potentials fire action potentials when they
Ø Occurs as a result of changes in membrane potential (Calcium enters the reach threshold.
cytosol from the ECF due to membrane depolarization that results in

Membrane potential
opening of voltage gated Ca++ channels) Action potentials

Ø Neurotransmitters or hormones causing depolarization will result in Threshold

contraction, while those causing hyperpolarization will result in relaxation.

Slow wave potential
Ø Membrane potentials are categorized as:
Time
a) Slow wave potentials – cyclic depolarization and repolarization of the
cell membrane. Creates intermittent waves of contraction, not all of Pacemaker potentials always depolarize to threshold.
which will reach threshold (slow waves of depolarization and

Membrane potential
repolarization that build up to reach threshold potential and trigger
action potentials that will cause contraction).
b) Pacemaker potentials – the membrane potential oscillates between Threshold
regular depolarizations to threshold that fire action potentials at Pacemaker potential

regular intervals. Creates steady rhythmic contraction Time

Ø E.g. the smooth muscle of the gastrointestinal tract has both pacemaker
potentials and slow wave potentials. Fig. 12.28
J) Smooth Muscle: Physiology
Ø Excitation Contraction Coupling in Smooth Muscle:
Ø 2 mechanisms:
2. Pharmacomechanical coupling
Ø Does NOT involve changes in membrane potential or the
opening of voltage-gated calcium channels in the sarcolemma.
Ø Ca++ enters through non-voltage gated channels or via GPCRs
or tyrosine kinases and second messenger systems that open
calcium channels on the SR.
Ø IP3 activation of IP3 channel receptors on the SR membrane
is the predominant form of pharmacomechanical coupling
in smooth muscle cells Histamine
Nitric oxide
Ø E.g. the actions of nitric oxide or histamine which activate
GPCRs and second messenger pathways on smooth muscles in
the airways and blood vessels.

After Fig. 12.28

K) Cardiac Muscle: Structure
Ø Cardiac muscle cells:
Ø form both the contractile myocardium (the
cardiac muscle tissue that contracts) and the
intrinsic conduction system (part of the heart
that generates and conducts electrical
impulses.
Ø have some similarities to skeletal muscle,
including:
1. Striations (the cells contain myofibrils with
sarcomeres that have the exact same
arrangement of thick and thin filaments).
2. The presence of the sarcoplasmic reticulum
and T-tubules surrounding the myofibrils.
K) Cardiac Muscle: Structure
Ø Cardiac muscle cells:
Ø have some differences compared to skeletal muscle fibers
including:
1. Smaller cells
2. uninucleated cells – have only a single nucleus
3. branched cells – the cells and their myofibrils do not always Fig. 14.5
run parallel to one another, but form branches that help to
interconnect the cells.
4. intercalated discs = region where two cells meet that
interconnects the cells to form a functional syncytia (i.e. the
connections between cells allow cells to act as a single unit).
Ø within the intercalated disc there are:
a) anchoring junctions (desmosomes) – keep cell physically
connected to one another and allow force of contraction to
be spread across all cells
b) gap junctions – allow ions and molecules to pass directly (&
quickly) from one cell to another. Provides electrical connection
between cells. Fig. 14.9
K) Cardiac Muscle: Structure
Ø Cardiac muscle cells:
Ø have some differences compared to skeletal muscle fibers
including:
5. T-tubules are larger in diameter.
6. Sarcoplasmic reticulum is smaller (lacks terminal cisternae)
7. Mitochondria – are larger and occupy ~25-33% of the cell
volume (compared to skeletal muscle cells where mitochondria
are smaller and more numerous, but occupy only ~2% of the
cell).
K) Cardiac Muscle: Structure
Ø 3 types of cardiac muscle cells:
1. Myocardial Contractile Cells (working cells)
Ø 99% of cardiac muscle cells
Ø contractile, MUSCLE part of the heart, do the mechanical
work of pumping
Ø striated fibers, containing myofibrils made up of sarcomeres
Ø joined electrically by gap junctions

2. Myocardial Autorhythmic (Pacemaker) Cells

Ø Located in sinoatrial node and atrioventricular node of
conduction system
Ø initiate signal (AP) for contraction and maintain electrical
activity in the heart = pacemakers
Ø smaller and fewer contractile fibers compared to contractile
cells
Ø do not have organized sarcomeres
Ø do not contract
K) Cardiac Muscle: Structure
Ø 3 types of cardiac muscle cells:
3. Conducting Cells
Ø carry electrical signals from the pacemakers (autorhythmic
cells) to the contractile cells and cause contractile cells to
depolarize and have an action potential
Ø structurally similar to autorhythmic cells
L) Cardiac Muscle: Physiology
Ø We will look at the specifics of the action potential in pacemaker cells and contractile cells when
we cover the Cardiovascular System in BIOL2420 – Human Physiology 2
Ø For now, just for comparison to Skeletal and Smooth Muscle, let’s take a look at how excitation
contraction coupling works in contractile cells
L) Cardiac Muscle: Physiology
Ø Excitation Contraction Coupling in Contractile Myocardial Cells
How does the action potential in a cardiac contractile cell
stimulate contraction of the cell (and therefore the heart).
a. Contractile cell depolarizes and action potential on sarcolemma causes…. a
b. Opening of voltage gated Ca++ channels (DHP/L-type calcium
channels) on the membrane (T-tubule). Calcium enters the cell.
a
c. Ca++ binds to ryanodine receptor (RyR) Ca++ release channel NCX
on the membrane of the sarcoplasmic reticulum (SR). f
d. RyR channel opens and Ca++ is released into the cytosol. This Ca2+
process is described as Ca++ induced Ca++ release (similar to ATPase

smooth muscle) , which leads to a Ca++ signal.

e

e. Ca++ ions bind to troponin (similar to skeletal muscle), initiating

the contraction cycle and crossbridge formation (myosin binds to
b d
actin, power stroke, etc).
f. Relaxation of the cell involves: Ca++ ATPase pumping Ca++ into
the SR. Na+/ Ca++ Exchanger (NCX), an antiport that moves Ca++
out of cell in exchange for Na+ (similar to smooth muscle). As c
Ca++ levels in the cytosol decrease, Ca++ unbinds from troponin,
stopping the contraction cycle. After Stokke et al. 2012. From global to local: a new understanding of cardiac
Similar to Figure 14.10 electromechanical coupling. Tidsskr Nor Laegeforen. 132: 1457-1460.
M) Comparison of 3 Muscle Types
Know This Table!
Table 12.4
UNIT 8: MUSCLES
BIOL2410 D01 Lecture Notes
A) Overview
A critical function of the somatic and autonomic nervous systems is the
control of skeletal muscle , smooth muscle, and cardiac muscle. Muscle
contractions produce movements that allow the body to accomplish
several functions that are essential for homeostasis. These include (but
are certainly not limited to):
• procuring and chewing food for the intake of nutrients (skeletal muscle)
• shivering to help maintain body temperature (skeletal muscle)
• mechanical digestion of ingested food and elimination of indigestible
waste (smooth muscle of digestive tract)
• circulating gases and nutrients to tissues and removal of wastes (cardiac
muscle of the heart and smooth muscle of blood vessels).
• Etc.
In this unit we will examine the structure and function of the three
different muscle types in the body: skeletal, smooth, and cardiac muscle.
Quilled paper anatomical art series (Sarah Yakawonis
2013 https://medinart.eu/works/sarah-yakawonis/)
A) Overview
1. Types of Muscle Tissue
2. Structure of Skeletal Muscle
3. Physiology of Skeletal Muscle
4. Skeletal Muscle Fibre Contraction
5. Clinical Applications of Skeletal Muscle Contraction
6. Energy use by skeletal muscle cell
7. Adjusting tension in skeletal muscle cells and whole muscles.
8. Mechanics of body movement
9. Structure of Cardiac Muscle
10.Physiology of Cardiac Muscle
11. Structure of Smooth Muscle
12.Physiology of Smooth Muscle
Quilled paper anatomical art series (Sarah Yakawonis
2013 https://medinart.eu/works/sarah-yakawonis/)
 B) Types of Muscle Tissue Fig. 12.1

1. Skeletal Muscle
a. Part of the muscular system that controls
voluntary body movement.
Ø Usually attached to bones by tendons
Ø E.g. muscle tissue found in biceps and triceps.
b. General properties of cells:
i. Multinucleated cells (many nuclei per cell)
ii. Striated (striped pattern formed from
overlapping proteins).
iii. Long cells, stacked in parallel
Ø A single skeletal muscle cell can run the
length of a whole muscle.
Ø The longest skeletal muscle cells in the human body are found
in the sartorius muscle of the leg and can be up to 60 cm long.
c. Controlled by somatic nervous system (contraction is
voluntary/under conscious control)
sartorius
B) Types of Muscle Tissue Fig. 12.1

2. Cardiac Muscle
a. Muscle tissue that controls the involuntary
contractions of the heart.
Ø Contractions act as a pump to move blood
through the cardiovascular system.
b. General properties of cells:
i. Uninucleated cells (one nucleus per cell)
ii. Striated (striped pattern along cells formed
from overlapping proteins).
iii. Shorter cells, stacked end to end.
Ø Cell ends are connected to one another by
intercalated disks that have many gap junctions.
c. Contraction occurs spontaneously (initiated by specialized
cardiac muscle cells within the heart itself). Rate of contraction
is modified by the autonomic nervous system and endocrine
system. Contraction is involuntary/not under conscious control.
B) Types of Muscle Tissue Fig. 12.1

3. Smooth Muscle
a. Muscle tissue that controls the involuntary
contractions of internal organs and tubes
(except for the heart).
Ø For example: walls of the stomach, small and
large intestines, blood vessels, bladder, and
uterus. Also pupillary muscles.
b. General properties of cells:
i. Uninucleated cells (one nucleus per cell)
ii. NOT striated (gives smooth appearance)
iii. Short spindle shaped cells, organized into sheets or tubes.
c. Contraction may occur spontaneously (often in response to
stretch); but also responds to signals from autonomic nervous
system and endocrine system. Contraction is involuntary/not
under conscious control.
C) Skeletal muscle: Structure
Ø General Characteristics of Whole Muscles:
1. Usually attached to bones by tendons (tendons are dense
irregular connective tissue that contains a lot of collagen)
2. Attachment points of a muscle are called:
a. Origin: attachment of the muscle that is closer to the trunk of the
body or that is the more stationary bone during muscle
contraction. E.g. Biceps has origin on the scapula (shoulder blade)
b. Insertion: more distal (further from the trunk) or mobile
bone/attachment. E.g. Biceps has insertion on the radius.
3. Muscles can be described by their actions:
a. Flexor: decreases the angle between two bones (bringing them
closer together). E.g. Biceps moves radius towards the humerus.
b. Extensor: Increases the angle between two bones (moving them
apart). E.g. Triceps moves ulna away from humerus.

Fig. 12.2
C) Skeletal muscle: Structure
Ø General Characteristics of Whole Muscles:
4. Antagonistic muscle groups are pairs or groups of muscles
that have opposite actions.
Ø All flexor-extensor pairs that move bones in opposite directions
around a joint are antagonists . E.g. the bicep and tricep are an
antagonistic muscle group since they have opposite actions
(flexion and extension) at the elbow joint.
Ø In order for movement to occur at a joint, one muscle in an
antagonistic pair must relax while the other contracts.

Fig. 12.2
C) Skeletal muscle: Structure
Ø General Characteristics of Whole Muscles:
5. A whole muscle consists of a group of fascicles held together by connective tissue that are supplied
by blood vessels and nerves.
Ø Each fascicle is a group (bundle) of muscle fibers (cells) lying parallel to one another that are also joined to
one another by connective tissue.

Fig. 12.3a
C) Skeletal muscle: Structure
Ø Structure of Skeletal Muscle Fibers (cells):
1. Sarcolemma = muscle cell membrane
Ø Is electrically excitable (stimulated by lower motor
neuron at the neuromuscular junction (see Unit 7 notes).
2. Sarcoplasm = cytoplasm of muscle cell
3. Sarcoplasmic reticulum = extensive network of smooth
endoplasmic reticulum of muscle cell. Terminal cisternae Triad

Fig. 12.3a
C) Skeletal muscle: Structure calsequestrin

Ø Structure of Skeletal Muscle Fibers (cells):

1. Sarcolemma = muscle cell membrane
Ø Is electrically excitable (stimulated by lower motor
neuron at the neuromuscular junction (see Unit 7 notes).
2. Sarcoplasm = cytoplasm of muscle cell
3. Sarcoplasmic reticulum = extensive network of smooth
endoplasmic reticulum of muscle cell.
Ø Membranous tubes with enlarged ends called terminal cisternae
Ø Has a very high Ca++ concentration due to:
a) Ca++ ATPase transporter in SR membrane (uses ATP to pump
Ca++ from cytosol into SR)
b) Presence of a Ca++ binding protein called calsquestrin, which
binds to Ca++ thereby reducing effective Ca++ concentration
so that the Ca++ ATPase can continue to pump Ca++ into SR
Ø Stores calcium ions (Ca2+) that can be released into Tortora, G.J. and Derrickson, B.H. (2021). Principles of Anatomy
cytosol to initiate contraction and Physiology 16th edition. John Wiley and Sons, Inc.
C) Skeletal muscle: Structure
Ø Structure of Skeletal Muscle Fibers (cells):
4. Myofibrils = long rods of protein in the cytoplasm of the
muscle fiber that run the length of the cell.
Ø Each myofibril is composed of individual units called sarcomeres,
which are the functional unit of muscle contraction.
Ø are anchored to the cell membrane by the protein dystrophin.
Ø Duchenne muscular dystrophy is an X-linked recessive
inherited disorder in which a mutation in the gene that codes
for the dystrophin protein prevents muscle cells from
producing functional dystrophin. Without a mechanism to
anchor myofibrils (and therefore transmit their contraction) to
the cell membrane, muscles become weak and easily
damaged.

Tortora, G.J. and Derrickson, B.H. (2021). Principles of Anatomy

and Physiology 16th edition. John Wiley and Sons, Inc.
C) Skeletal muscle: Structure
Ø Structure of Skeletal Muscle Fibers (cells):
5. Transverse tubules (T-tubules) = part of sarcolemma
that folds into the inside of the cell at regular
intervals (at junction of A and I bands of sarcomeres)
and surrounds each of the myofibrils. Lumen of
tubule is filled with extracellular fluid.
Ø 1 T-tubule plus the 2 terminal cisternae on either side of
it is called a triad.
ØT-tubules carry action potentials from the sarcolemma
deep into the cell. This ensures that the signals for
muscle cell contraction reach all of the sarcomeres in all
of the myofibrils in a cell (even the ones furthest away
from the surface of the cell).
6. Many mitochondria and glycogen granules in
Fig. 12.4
sarcoplasm because muscle contraction requires a lot
of ATP.
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Several hundreds to thousands of myofibrils in each fiber (cell).
Ø Each myofibril in composed of sarcomeres stacked end to end.
Ø Sarcomeres are composed of several different proteins most of Thin filaments (red) Thick filaments (blue)
which are arranged into two types myofilaments:
1. Thick myofilaments composed of:
a. Myosin – functions in contraction
Ø Protein molecule consists of two identical subunits shaped like
a golf club
Ø Tail ends intertwined around each other, globular heads project
out at one end
Ø Myosin tails are oriented toward the center of the filament
and globular heads protrude at regular intervals

Fig. 12.3a
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres: Crossbridge
ADP
Ø Several hundreds to thousands of myofibrils in each fiber (cell). Pi

Ø Each myofibril in composed of sarcomeres stacked end to end.

Ø Sarcomeres are composed of several different proteins most of
which are arranged into two types myofilaments:
1. Thick myofilaments composed of:
a. Myosin – functions in contraction
Ø Myosin heads **form crossbridges** between thick and thin
filaments by binding to G-actin (a protein of thin filament).
Ø Myosin head has 2 important sites critical to contractile Actin Binding Site
process:
ATPase
i. Actin binding site (ATP Binding Site)

ii. Myosin ATPase (ATP binding site) - myosin is an ATPase

(similar to Na+/K+ ATPase). It breaks down ATP
through hydrolysis into ADP and Pi and stores the
released energy to be used to pivot the myosin head
during contraction. Fig. 12.3a
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Several hundreds to thousands of myofibrils in each fiber (cell).
Ø Each myofibril in composed of sarcomeres stacked end to end.
Ø Sarcomeres are composed of several different proteins most of Thin filaments (red) Thick filaments (blue)
which are arranged into two types myofilaments:
2. Thin myofilaments composed of: Thin filaments
a. G-Actin – functions in contraction (G stands for globular, since
the actin protein is in its globular form)
Ø Primary structural protein of thin filaments Titin

Ø G-actin monomers are spherical (globular) but assembled

into long chains. Troponin Nebulin

Ø Each actin molecule has special binding site for attachment

of the myosin head. Binding (crossbridge formation) and
movement of the myosin head results in contraction of the Tropomyosin Myosin binding
G-actin molecule
site (yellow)
sarcomeres and of the muscle fiber (cell). Actin chain
Fig. 12.3a
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Several hundreds to thousands of myofibrils in each fiber (cell).
Ø Each myofibril in composed of sarcomeres stacked end to end.
Ø Sarcomeres are composed of several different proteins most of Thin filaments (red) Thick filaments (blue)
which are arranged into two types myofilaments:
2. Thin myofilaments composed of: Thin filaments
b. Tropomyosin
Ø Regulatory protein (regulates contraction of the sarcomere)
Ø Thread-like proteins that runs the length of the outer surface Titin

of the actin chain.

Ø In a relaxed sarcomere, tropomyosin covers the myosin Troponin Nebulin

binding site on actin. So, for contraction to occur,

tropomyosin must be moved in order to uncover/reveal the
binding sites. Tropomyosin Myosin binding
G-actin molecule
site (yellow)
Actin chain
Fig. 12.3a
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Several hundreds to thousands of myofibrils in each fiber (cell).
Ø Each myofibril in composed of sarcomeres stacked end to end.
Ø Sarcomeres are composed of several different proteins most of
which are arranged into two types myofilaments:
2. Thin myofilaments composed of: Thin filaments
c. Troponin
Ø Also a regulatory protein (regulates contraction of the
sarcomere) Titin

Ø Composed of 3 polypeptide units

i. One binds to tropomyosin (troponin T) Troponin Nebulin

ii. One binds to actin (troponin I)

iii. One can bind with Ca++ (troponin C)
Myosin binding
Tropomyosin G-actin molecule
site (yellow)
Actin chain
Fig. 12.3a
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Several hundreds to thousands of myofibrils in each fiber (cell).
Ø Each myofibril in composed of sarcomeres stacked end to end.
Ø Sarcomeres are composed of several different proteins most of
which are arranged into two types myofilaments:
2. Thin myofilaments composed of:
c. Troponin
Ø when not bound to Ca2+, troponin stabilizes tropomyosin
over actin’s cross-bridge binding sites. This blocks myosin
from being able to bind to actin.

Troponin not bound to Ca++

Fig. 12.8
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Several hundreds to thousands of myofibrils in each fiber (cell).
Ø Each myofibril in composed of sarcomeres stacked end to end.
Ø Sarcomeres are composed of several different proteins, most of
which are arranged into two types myofilaments:
2. Thin myofilaments composed of:
c. Troponin
Ø when not bound to Ca2+, troponin stabilizes tropomyosin
over actin’s cross-bridge binding sites. This blocks myosin
from being able to bind to actin.
Ø When Ca2+ binds to troponin, tropomyosin moves away from
blocking position
Ø With tropomyosin out of way, the binding sites on actin are Troponin bound to Ca++ (step 2)
revealed, and the myosin head binds to actin forming a
crossbridge that will allow contraction to occur. Fig. 12.8
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Other protein components of the sarcomeres include:
3. Z-disks
Ø Connect sarcomeres (between two Z-disks = 1 sarcomere).
Ø Point of attachment for thin filaments and titin.
4. M-line
Ø Made of the protein myomesin
Ø Runs down the middle of the sarcomere
Ø Point of attachment for myosin (thick filaments) and titin.
5. Titin – aligning protein
Ø Large elastic protein.
Ø Joins M-line proteins to Z-disks at opposite ends of the sarcomere
Ø 2 important roles:
a. Stabilizes position of thick filaments in relation to thin filaments
b. Improves muscle elasticity (allows muscle to return to resting Fig. 12.6
length after contraction)
C) Skeletal muscle: Structure
Ø Structure of Myofibrils and Sarcomeres:
Ø Other protein components of the sarcomeres include:
6. Nebulin – aligning protein
Ø Aligns actin chains

Fig. 12.6
C) Skeletal muscle: Structure Fig. 12.3

Ø Structure of Myofibrils and Sarcomeres:

Ø Pattern of overlap of thick and thin myofilaments in
sarcomeres creates the striations (striped appearance) seen in
skeletal (and cardiac) muscle cells. The sarcomere is divided A band
Z-line
A band
Sarcomere

A band
A band
into different bands or zones depending on the proteins
present. The banding pattern includes:
I band I band I band
1. A band – contains both actin and myosin (thin and thick H zone
M-line Fig. 12.5
myofilaments)
Ø Dark band that is the length of the thick filament (myosin)
Ø Includes areas where thick and thin filaments overlap
Ø M-line is in the center of the A band.
Ø Does not change length during contraction.
2. H-zone – contains myosin only
Ø Lighter band at center of A band
Ø Shortens and disappears during contraction as myosin and
actin become progressively more overlapped.
C) Skeletal muscle: Structure Fig. 12.3

Ø Structure of Myofibrils and Sarcomeres:

Ø Pattern of overlap of thick and thin myofilaments in
sarcomeres creates the striations (striped appearance) seen in
skeletal (and cardiac) muscle cells. The sarcomere is divided A band
Z-line
A band
Sarcomere

A band
A band
into different bands or zones depending on the proteins
present. The banding pattern includes:
I band I band I band
3. I-band – contains thin filament (actin) only H zone
M-line Fig. 12.5
Ø Light band that spans two adjacent sarcomeres.
Ø Shortens during contraction
Ø Z-disk is in the center of the I-band.

Ø Sarcomeres join end to end at Z-disks to form myofibrils

C) Skeletal muscle: Structure Fig. 12.3

Ø Summary of skeletal muscle structure:

C) Skeletal muscle: Physiology Similar to figure 8.1

Ø Control by the Nervous System:

Ø Skeletal muscle contraction is controlled by neurons in
CNS PNS
CNS and Somatic nervous system (a division of the
peripheral nervous system).
Sensory Efferent (motor)

Somatic Autonomic

SNS
PSNS

After Marieb and Hoehn 2019

C) Skeletal muscle: Physiology Primary
motor cortex

Ø Control by the Nervous System:

Ø Skeletal muscle contraction is controlled by neurons in
CNS and Somatic nervous system (a division of the Upper
peripheral nervous system) motor
neurons
Ø Two neuron pathway from the brain to the muscle: lower motor neurons

1. Upper Motor Neurons with cell bodies in the primary motor Cranial nerve

cortex synapse on lower motor neurons in the ventral horn lneurons

to selected MIDBRAIN
skeletal muscles
of the spinal cord. lower motor neurons

2. Lower Motor Neurons with cell bodies in ventral horn of

MEDULLA
spinal cord send axons to synapse on skeletal muscle cells. OBLONGATA

Pyramids

Somatic neurons
to
skeletal muscles SPINAL CORD
lower motor neurons

Fig 13.10
C) Skeletal muscle: Physiology
One muscle may have
Ø Control by the Nervous System: many motor units of
different fiber types.
SPINAL CORD

Ø Skeletal muscle contraction is controlled by neurons in

CNS and Somatic nervous system (a division of the
peripheral nervous system)
Ø Two neuron pathway from the brain to the muscle: Neuron 1
Neuron 2
1. Upper Motor Neurons with cell bodies in the primary motor Neuron 3

cortex synapse on lower motor neurons in the ventral horn Motor

nerve
of the spinal cord.
KEY
2. Lower Motor Neurons with cell bodies in ventral horn of Motor unit 1

spinal cord send axons to synapse on skeletal muscle cells. Muscle Motor unit 2
fibers
Ø One lower motor neuron can synapse on one or many Motor unit 3

skeletal muscle cells. But each skeletal muscle cell receives

ONLY ONE synapse.
Fig 12.17
Ø The group of muscle cells that are innervated by a single
lower motor neuron is called a motor unit. A motor unit
can have as many as 1000 cells innervated by a single
neuron.
C) Skeletal muscle: Physiology
Ø Control by the Nervous System:
Ø Action potentials sent by upper motor neurons to lower motor neurons eventually arrive at the
neuromuscular junction (the synapse between the axon terminal of a lower motor neuron and a skeletal
muscle cell). See Unit 7 notes (part of which are shown below) for a description of the structure and
events at the neuromuscular junction.
D) Skeletal muscle fibre contraction Fig. 12.7

Ø Skeletal muscle contraction begins with a resting muscle

fibre (cell). This cell is then stimulated due to the events at
the neuromuscular junction. Once an action potential is
created on the sarcolemma of the skeletal muscle cell, it
must be converted into an intracellular signal that leads to
contraction. We will examine this process in 6 major steps:
1. Conditions in the Relaxed/Resting Muscle Fibre (starting
point)
2. Events at the neuromuscular junction
3. Action potentials on the sarcolemma
4. Excitation contraction coupling
5. Muscle fibre contraction (=Sliding Filament Mechanism).
6. Muscle fibre relaxation
D) Skeletal muscle fibre contraction Fig. 12.7

1. Conditions in the Relaxed/resting Muscle Fibre

Ø tropomyosin covers myosin binding sites on actin
Ø myosin heads are activated – ready and waiting to bind to
actin the moment the binding sites are uncovered/revealed.
Ø Activation of the myosin head occurs when the myosin head
hydrolyzes ATP into ADP and Pi (inorganic phosphate). The ADP
and Pi remain attached to the myosin head until the power stroke
of contraction occurs.
D) Skeletal muscle fibre contraction
2. Events at the neuromuscular junction
Ø Steps:
1. Action potential (AP) arrives at axon terminal
2. Change in membrane potential due to AP triggers opening
of voltage gated Ca++ channels.
3. Ca++ diffuses into axon terminal
4. Rise in intracellular Ca++ triggers exocytosis of vesicles
containing the neurotransmitter acetylcholine (ACh).
5. ACh diffuses across the synaptic cleft and two Ach molecules
bind to each NM nicotinic cholinergic receptor (nAChRs) on the
motor end plate.
6. nAChR channels open and allow Na+ and K+ to move through
the channel.
7. Net Na+ influx into the skeletal muscle cell causes depolarization
of the skeletal muscle cell – a graded potential called an End
Plate Potential (EPP).
Fig. 11.10
D) Skeletal muscle fibre contraction
2. Events at the neuromuscular junction
Ø The depolarizing graded potential (End plate potential) on
the motor end plate is a type of EPSP (excitatory postsynaptic
potential) that will always lead to an action potential on the
sarcolemma of the skeletal muscle cell. This is due to:
1. The large amount of ACh that is released from the axon terminal
of the neuron
2. The large number of nAChRs on the motor end plate.
Fig. 12.10a
3. The high density of voltage gated Na+ channels in the motor
end plate and adjacent sarcolemma.
Ø 1 & 2 combine to create a large enough depolarization (EPSP) that
causes the skeletal muscle cell membrane potential to reach
threshold without having to rely on summation of EPSPs (as might
be the case in a neuron).
Ø At threshold the many voltage gated Na+ channels in the motor
end plate and adjacent sarcolemma all open, and an action
potential on the sarcolemma of the skeletal muscle cell begins.
D) Skeletal muscle fibre contraction
3. Action potentials on the sarcolemma
Ø The resting membrane potential of a skeletal muscle cell is -
90mV (close to the equilibrium potential for K+).
Ø The EPP depolarizes the muscle cell to threshold
Ø At threshold the many voltage-gated Na+ channels in the
motor end plate and adjacent sarcolemma all open, and an
action potential on the sarcolemma of the skeletal muscle cell Marieb and Hoehn 2019
begins. This action potential has similar properties and uses
similar channels to the action potentials observed in neurons.
a) The EPP triggers the opening of fast Na+ voltage gated channels and
slow K+ voltage gated channels.
b) Na+ enters the muscle cell depolarizing the membrane potential.
c) Na+ voltage gated channels become inactivated and K+ voltage
gated channels become fully open leading to repolarization of the cell
as positive charges are lost in the form of K+.
d) K+ voltage channels close and the membrane potential returns to rest.
D) Skeletal muscle fibre contraction
3. Action potentials on the sarcolemma
Ø The action potential propagates along the sarcolemma and
moves along T-tubules to deep within the muscle fibre

Marieb and Hoehn 2019

D) Skeletal muscle fibre contraction
4. Excitation Contraction Coupling
Ø Converts electrical event of action
potential in the T-tubule into intracellular
events that lead to contraction.
Ø Steps:
a) AP in T-tubule stimulates a conformation (shape)
change in a voltage sensitive membrane protein
called the DHP (dihydropyridine) receptor.
b) DHP receptor touches the Ryanodine Receptor
(RyR) (a mechanically gated Ca++ channel) on
the sarcoplasmic reticulum (SR) and opens it.
Fig. 12.10b
c) Ca++ flows out of the SR into the cytosol (down
its concentration gradient).
d) Ca++ in the cytosol binds to troponin
e) Troponin-tropomysin complex moves revealing
the myosin binding sites on actin.
D) Skeletal muscle fibre contraction
5. Muscle Fibre Contraction – Sliding Filament Theory
Ø Mechanical events of contraction.
Ø Steps:
a) Activated myosin heads attach to binding sites on
actin = crossbridge formation
b) Power stroke occurs à Pi (inorganic phosphate),
ADP and energy stored in the myosin head are
released causing the myosin head to pivot
c) The myosin head pulls actin so that actin (thin
filament) slides over myosin (thick filament) toward
the center of the sarcomere (M-line).
Fig. 12.10b
d) ATP attaches to the myosin head, causing it to disconnect
from actin (crossbridge detachment)
e) The myosin head hydrolyzes ATP into ADP + Pi, which
reactivates the myosin head.
D) Skeletal muscle fibre contraction
5. Muscle Fibre Contraction – Sliding Filament Theory Fig. 12.9
Ø Mechanical events of contraction.
Ø Steps:
a) Activated myosin heads attach to binding sites on
actin = crossbridge formation
b) Power stroke occurs à Pi (inorganic phosphate),
ADP and energy stored in the myosin head are
released causing the myosin head to pivot
c) The myosin head pulls actin so that actin (thin
filament) slides over myosin (thick filament) toward
the center of the sarcomere (M-line).
d) ATP attaches to the myosin head, causing it to disconnect
from actin (crossbridge detachment)
e) The myosin head hydrolyzes ATP into ADP + Pi, which
reactivates the myosin head.
f) As long as Ca++ in the cytosol remains high and binding sites
on actin are exposed, the myosin heads will repeatedly bind to
actin, undergo a power stroke, release and reactivate to bind
again (= crossbridge cycling
D) Skeletal muscle fibre contraction
5. Muscle Fibre Contraction – Sliding Filament Theory Fig. 12.9
Ø Mechanical events of contraction.
Ø Steps:
a) Activated myosin heads attach to binding sites on
actin = crossbridge formation
b) Power stroke occurs à Pi (inorganic phosphate),
ADP and energy stored in the myosin head are
released causing the myosin head to pivot
c) The myosin head pulls actin so that actin (thin
filament) slides over myosin (thick filament) toward
the center of the sarcomere (M-line).
d) ATP attaches to the myosin head, causing it to disconnect
from actin (crossbridge detachment)
e) The myosin head hydrolyzes ATP into ADP + Pi, which
reactivates the myosin head.
f) As long as Ca++ in the cytosol remains high and binding sites
on actin are exposed, the myosin heads will repeatedly bind to
actin, undergo a power stroke, release and reactivate to bind
again (= crossbridge cycling) which shortens the sarcomeres.
D) Skeletal muscle fibre contraction
5. Muscle Fibre Contraction – Sliding Filament Theory
Ø When sarcomeres shorten the banding
pattern (striations) change
Ø H zone, I band shorten
Ø A band, remains the same length

Ø Shortening of a whole muscle results from

sarcomeres shortening, which shortens the
myofibrils in the muscle fibre (cell) which
shortens the muscle fibre, which shortens
fascicles which shortens the whole muscle.

Ø Throughout contraction the thin (actin) and Fig. 12.5d-e

thick (myosin) filaments remain the same length.

Marieb and Hoehn 2019

D) Skeletal muscle fibre contraction
5. Muscle Fibre Relaxation
Ø Steps:
a) Action potentials stop arriving at neuromuscular junction
b) Neurotransmitter on motor end plate (acetylcholine) is
broken down by enzyme acetylcholinesterase .
c) Ryanodine receptor channels (mechanically gated Ca++
channels) close – no more Ca++ into cytosol
d) Ca++ ATPase actively pump free calcium back into
sarcoplasmic reticulum and cytosolic [Ca++] decreases.
e) Decreased cytosolic [Ca++] causes Ca++ to dissociate
from troponin, and this Ca++ is also pumped into SR.
f) Tropomyosin moves back into position covering the Fig. 12.10c
myosin binding sites on actin. Without any crossbridges
forming the muscle fails to maintain tension.
g) Actin and myosin slip past one another back to their
resting positions (due in part to recoil of titin protein and
action of the antagonistic muscle).
E) Clinical Applications of Sk. Muscle Contraction
1. Rigor Mortis
Ø “stiffness of death”
Ø Occurs ~3-4 hours after death and peaks at ~12
hours.
Ø After death, intracellular Ca2+ rises (leaks out of SR)
Ø Ca2+ allows troponin-tropomyosin complex to move
aside and allow myosin heads to bind to actin
(crossbridge formation). ATP binds to myosin.
Ø But…. Myosin releases actin.

Ø ATP is needed to separate myosin from actin.

Ø Dead cells cannot produce more ATP.
Ø So once bound, cross bridges cannot detach. ATP binds.

Ø Rigor mortis subsides when enzymes start to break

down myosin heads
E) Clinical Applications of Sk. Muscle Contraction
2. Myasthenia Gravis
Ø “severe muscular weakness”
Ø An autoimmune disease of the neuromuscular junction.
Ø Autoantibodies bind to nicotinic acetylcholine receptors
(AChR).
Ø Acetylcholine can no longer bind to AChR (the antibody is a
competitive inhibitor), which prevents transmission of action
potentials to skeletal muscle cells.
Ø Result is flaccid paralysis of the muscle (no voluntary control of
the muscle and muscle cannot even maintain muscle tone
because no neural signals can reach the muscle).
Ø Treatment = drugs that inhibit acetylcholinesterase (AChE),
which will allow ACh to remain in the neuromuscular junction
longer to promote binding to any remaining functioning
receptors. Also immunosuppressive therapy to suppress
antibody production making more AChR available. http://www.chop.edu/conditions-diseases/myasthenia-gravis#.Vre4q8fZfww
E) Clinical Applications of Sk. Muscle Contraction
2. Myasthenia Gravis
Ø Symptoms include:
Ø Widespread skeletal muscle weakness that can cause
Ø Drooping eyelid
Ø Blurred or double vision
Ø Chronic muscle fatigue
Ø Slurred speech
Ø Difficulty breathing (diaphragm is skeletal muscle)

http://www.chop.edu/conditions-diseases/myasthenia-gravis#.Vre4q8fZfww
F) Energy Use In Skeletal Muscle
Ø Muscles need a constant supply of ATP for:
1. Myosin ATPase activity involved in the Power Stroke
(contraction of muscle cell)

2. Ca++ ATPase activity – for active transport of Ca++ back

ATP
into sarcoplasmic reticulum (relaxation of muscle cell) Ca2+

3. Na+/K+ ATPase activity – restores ion balance during

action potentials on muscle cell membrane
F) Energy Use In Skeletal Muscle
Ø Sources of ATP for muscle contraction:
1. Stored ATP (very little is stored)
2. Creatine phosphate (C~P)
Ø formed during resting conditions when ATP demand is
low (ATP + Creatine ⇌ ADP + C~P). Reaction is
mediated by the enzyme creatine kinase.
Ø First store of energy used at the onset of contractile
activity.
Ø During the first few minutes of exercise creatine kinase
converts ADP +C~P ⇌ ATP + Creatine
Ø The ATP can then be used to power muscle contraction.
Ø Provides 4-5 times the energy of stored ATP
Ø Supply is very limited (lasts for only ~30 seconds during
high intensity exercise such as sprinting).

Fig 12.12
F) Energy Use In Skeletal Muscle
Ø Sources of ATP for muscle contraction:
3. Oxidative phosphorylation Mitochondria

Ø Occurs in mitochondria of muscle cells if sufficient

oxygen is present
Ø Process that provides energy during light to moderate
exercise Pyruvate

Ø Uses stores of glycogen in muscle (~30 minutes of CoA

Acetyl CoA Fatty acids
b-oxidation
moderate exercise) Ketone bodies

Ø Good yield of ATP (via the citric acid cycle and CO2 (in liver)

electron transport chain) Citric acid

cycle ATP

Ø Exercise that makes use of oxidative phosphorylation

High-E e-
as the main supply of ATP is known as “aerobic + H+ NH3 Some
amino
exercise”. acids

Ø To main adequate oxygen supply during exercise the Electron transport

body will: Chain/Oxidative
Phosphorylation

O2 ATP + H2O
F) Energy Use In Skeletal Muscle
Ø Sources of ATP for muscle contraction:
3. Oxidative phosphorylation Mitochondria

Ø Occurs in mitochondria of muscle cells if sufficient oxygen is

present
Ø Process that provides energy during light to moderate exercise
Ø Uses stores of glycogen in muscle (~30 minutes of moderate exercise) Pyruvate

Acetyl CoA Fatty acids

Ø Good yield of ATP (via the citric acid cycle and electron transport CoA b-oxidation
chain)
Ketone bodies
Ø Exercise that makes use of oxidative phosphorylation as the main CO2 (in liver)

supply of ATP is known as “aerobic exercise”. Citric acid

cycle ATP
Ø To main adequate oxygen supply during exercise the body will:
a) Increase the rate and depth of breathing (ventilation) High-E e-
+ H+ Some
NH3
b) Increase heart rate and force of contraction of the heart (increases amino
acids
cardiac output – the amount of blood exiting the heart over time).
Electron transport
c) Dilate blood vessels going to skeletal muscles (this is the effect of Chain/Oxidative
epinephrine when it binds to the beta-2 receptors in the smooth Phosphorylation

muscle cells of the blood vessel walls).

O2 ATP + H2O
F) Energy Use In Skeletal Muscle
Ø Sources of ATP for muscle contraction:
4. Anaerobic glycolysis Anaerobic glycolysis

Ø Occurs in cytosol of muscle cells during high intensity exercise (e.g.

sprinting) or when there is little oxygen reaching the muscle tissue.
Ø Primary source of ATP when oxygen supply is limited (during
intense exercise) Energy source: glucose
Ø Provides a rapid supply of ATP Glucose (from
glycogen breakdown or
• Fewer enzymes are involved compared to oxidative phosphorylation, so delivered from blood)
ATP production can occur faster.
Glycolysis
Ø Very low yield of ATP in cytosol

• Only 2 per glucose molecule O2

2 ATP
• Lactic acid, acidifies muscle and may contribute to fatigue net gain
Pyruvic acid
O2
Ø Duration of anaerobic glycolysis is limited Released Lactic acid
to blood

Oxygen use: None

Products: 2 ATP per glucose, lactic acid
Duration of energy provided: 30–40
seconds, or slightly more
F) Energy Use In Skeletal Muscle
Ø Muscle Fatigue
Ø Decrease in the maximal force of contraction in a muscle over time.
Ø Two major categories:
1. Central fatigue
Ø Originates in the CNS, related to psychological fatigue.

Fig. 12.13
F) Energy Use In Skeletal Muscle
Ø Muscle Fatigue
Ø Decrease in the maximal force of contraction in a muscle over time.
Ø Two major categories:
2. Peripheral fatigue
Ø Related to events at the neuromuscular junction or within muscle cell.
Ø Possible Causes:
a) Decreased release of Ach – fewer APs on sarcolemma
b) Acetylcholine receptor (AChR) desensitization – fewer APs on sarcolemma
c) Changes to the RMP of the muscle cell – high K+ in ECF of T-tubules
d) Impaired Ca++ release by sarcoplasmic reticulum
e) Depletion of energy sources (creatine phosphate, ATP, glycogen)
f) Accumulation of byproducts (H+, Pi, lactic acid) of muscle contraction that
then interfere with muscle APs or crossbridge formation.
i. For example, accumulation of Pi may slow release of Pi from the
myosin head (preventing the power stroke).
ii. Pi may combine with Ca++ to form calcium phosphate, which would
reduce the amount of Ca++ available to bind to troponin, which would Fig. 12.13
result in less crossbridge formation (weaker contraction)
 Slow-Twitch Oxidative Muscle Fibers.

F) Energy Use In Skeletal Muscle Note smaller diameter, darker color due to myoglobin.

Ø Muscle Fatigue & Types of Motor Units

Ø Different types of motor units are subject to different levels of
fatigue.
Ø 3 types of motor units:
1. Slow twitch oxidative (slow fatigue resistant)
Ø generate small amounts of tension slowly.
Ø uses oxidative phosphorylation (aerobic) for ATP supply
Ø capable of generating tension for long periods of time Cross section of slow-twitch muscle fibers
(LM ´ 170)
without running down energy stores
Ø large numbers of mitochondria (good supply of ATP)
Ø small fiber diameter
Ø well vascularized & have lots of myoglobin (to facilitate
oxygen transfer from blood)
Ø High levels of myoglobin make this muscle tissue dark in colour
(think of the dark meat in chicken legs/thighs).
Ø Found in endurance muscles such as postural muscles in legs/hips.
Fig. 12.13
Marathon runners have a high proportion of these fibres. Fig. 12.14
F) Energy Use In Skeletal Muscle
Ø Muscle Fatigue & Types of Motor Units
Ø Different types of motor units are subject to different levels of
fatigue.
Ø 3 types of motor units:
2. Fast oxidative-glycolytic (fast fatigue resistant)
Ø generate a lot of tension moderately fast
Ø Somewhat resistant to fatigue (intermediate)
Ø Moderate numbers of mitochondria
Ø Intermediate (medium) fiber diameter
Ø Intermediate levels of myoglobin that give the muscle a red
appearance (but not as red/dark as slow twitch oxidative
fibres).
 Fig. 12.14 Fast-Twitch Glycolytic Muscle Fibers.

F) Energy Use In Skeletal Muscle

Larger diameter, pale color. Easily fatigued.

Ø Muscle Fatigue & Types of Motor Units

Ø Different types of motor units are subject to different levels of
fatigue.
Ø 3 types of motor units:
3. Fast twitch glycolytic (fast easily fatigued)
Ø generate the most tension (force/power)
Ø fatigue rapidly
Cross section of fast-twitch muscle fibers (LM ´ 17
Ø few mitochondria (so employ anaerobic means of ATP
generation).
Ø large fiber diameter
Ø low levels of myoglobin that give the muscle a white
appearance (think of the white meat of a chicken breast).
Ø weightlifters (especially those who do deadlifts) build up
more fast twitch glycolytic fibers/motor units – produces a lot
of power over a short period of time.
G) Muscle Tension
Ø Muscle tension is the force exerted by a muscle or muscle fiber
Ø Tension is determined by the number of cross bridges formed
between myosin and actin.
Ø Increased number of crossbridges = increased tension
Ø Decreased number of crossbridges = decreased tension.
Ø The number of crossbridges formed is related to the amount of
Fig. 12.16
Ca++ in the cytosol that can bind to troponin. So…
Ø Increased cytosolic Ca++ = increased crossbridges = increased tension
Ø Decreased cytosolic Ca++ = decreased crossbridges = decreased tension.
Ø The amount of Ca++ in the cytosol is dependent on the frequency of action
potentials on the sarcolemma. If only one AP – calcium is released, but
immediately taken back up into SR by Ca++ ATPase pumps, but over multiple
APs more and more Ca++ is builds up in cytosol allowing more and more
crossbridges to form which produces higher and higher levels of tension.
G) Muscle Tension Fig 12.16a
Ø Muscle tension in a single muscle fiber is affected by:
1. Frequency of Stimulation
a) Single Stimulus
Ø Produces a twitch (a weak contraction and relaxation resulting from
one action potential going to one muscle fibre – this does not
normally occur in skeletal muscles and is only observed in the lab)
Ø Events:
i. 1 stimulus à 1 AP on sarcolemma (lasts 1-2 msec)
ii. Latent period (~2 msec) – period of time when excitation
contraction coupling is occurring
iii. Contraction period (~5-50 msec) – time when tension in the cell
increases to peak
Ø Ca++ is released from the SR on stimulation, but is rapidly taken
back into SR by action of Ca++ ATPase on SR membrane.
Ø Not enough Ca++, so not all myosin heads are able to bind to
actin (low crossbridge formation), so twitch does not reach
maximum possible tension
http://www.austincc.edu/rfofi/NursingRvw/PhysText/Muscle.html
G) Muscle Tension Fig 12.16a
Ø Muscle tension in a single muscle fiber is affected by:
1. Frequency of Stimulation
a) Single Stimulus
Ø Produces a twitch (a weak contraction and relaxation resulting from
one action potential going to one muscle fibre – this does not
normally occur in skeletal muscles and is only observed in the lab)
Ø Events:
iv. Relaxation period (~5-50 msec)
Ø Ca++ is pumped into SR, ATP binds to myosin head, myosin head
detaches from actin (crossbridge detachment)
Ø Result is decrease in tension

http://www.austincc.edu/rfofi/NursingRvw/PhysText/Muscle.html
G) Muscle Tension
Ø Muscle tension in a single muscle fiber is affected by:
1. Frequency of Stimulation
b) Summation of 2 stimuli
Ø Second stimulus arrives before complete relaxation produced by
the the first stimulus
Ø Action potential on sarcolemma is completed (and in its refractory
period), BUT the uptake of Ca++ by the SR is not yet complete
(the fibre is partially relaxed)
Ø 2nd stimulus causes release of more Ca++, adding to whatever is
still in the cytosol from the first stimulus. The combined Ca++ is
greater than the first stimulus alone, and so more crossbridges Fig. 12.16b
can form
Ø Produces a second contraction with higher tension than the first
(=wave summation)
Ø This is possible because contraction does not have a refractory
period
G) Muscle Tension
Ø Muscle tension in a single muscle fiber is affected by:
1. Frequency of Stimulation
c) Summation leading to unfused tetanus
Ø Multiple stimuli arrive on after the other, but not fast enough to
prevent relaxation between contractions.
Ø Each stimulus releases more and more Ca++ into the cytosol,
which further increases tension (wave summation over multiple
stimuli).
Ø Partial relaxation between contractions produces unfused
(incomplete) tetanus. The fibre may quiver due to the partial
relaxation in between contractions.
Ø Tetanus refers to the muscle cell contraction (it is not the bacterial
disease called tetanus that causes severe involuntary muscle
contractions).

Fig 12.16c
G) Muscle Tension
Ø Muscle tension in a single muscle fiber is affected by:
1. Frequency of Stimulation
d) Summation leading to fused tetanus
Ø High frequency of stimuli
Ø No relaxation between contraction produces a sustained
contraction = fused (complete) tetanus.
Ø During this time all troponin in the cell is saturated with Ca++
and the maximum number of crossbridges are formed.
Ø Fused (complete) tetanus is what is often normally observed
in the body, for example when holding a heavy box, many of
the muscle fibers in the biceps would be in fused tetanus to
hold the sustained contraction of that muscle.
Ø Eventually fatigue will cause the tension to decrease rapidly.

Fig 12.16d
G) Muscle Tension
Ø Muscle tension in a single muscle fiber is affected by:
2. Length of the muscle fibers (Length-Tension Relationships)
a) Resting fibre length is optimum for producing the most
tension
Ø At resting length, there is optimal overlap between thick
and thin filaments which allows for the maximum number
of crossbridges to form upon stimulation and therefore Fig 12.15
allows for maximum tension to be reached. Shorter
b) Tension decreases if fiber length is shorter or longer than
resting length
i. Shorter than resting length – thin filaments overlap and
interfere with crossbridge attachment (not all myosin heads can
reach actin binding sites because thin filaments are blocking
each other). Fewer crossbridges = less tension.
ii. Longer than resting length (stretched) – too little overlap of thick Longer
and thin filaments. Not all myosin heads can reach actin binding
sites so fewer crossbridges can form and not as musch tension
can develop.
G) Muscle Tension
Ø Muscle tension in a single muscle fiber is affected by:
3. Fibre size
Ø The larger the fiber size, the more tension it can develop (larger
fibers have more myofibrils, therefore more sarcomeres, therefore
more crossbridges can form).
Ø Fiber thickness can be increased with exercise (e.g. weight training)
and under the influence of testosterone or anabolic steroids.
Ø Example – Effects of bed confinement (limited movement) on muscle
composition. Bottom image = patient with ICU (intensive care unit)
acquired muscle weakness. Top image = control where patient not
exhibiting weakness. Lack of muscle use while confined to a bed in the
ICU causes atrophy of muscles that can be seen at fiber level. Known as
CIM = critical illness myopathy. Size of fibres decreases (loss of myofibrils).
Schefold et al. 2010.

4. Fatigue – reduces tension

G) Muscle Tension
Ø Muscle tension in a whole muscle is affected by:
1. Number of fibers contracting
Ø The more active motor units in a muscle, the greater the tension
produced
Ø Small units are recruited first, then larger ones are added when more
tension is needed.
2. Number of fibers per motor unit
Ø More fibres per motor unit = more tension produced
Ø 1 neuron innervating 10 fibers (small motor unit) produces weak
tension vs. 1 neuron innervating 1000 fibers (larger motor unit)
produces more tension.
3. Muscle size
Ø The larger the muscle, the more fibres there will be, and the more
tension the muscle can produce.
4. Muscle fatigue
Marieb and Hoehn 2019
H) Mechanics of Body Movement
Ø Types of whole muscle contraction
1. Isotonic
Ø Muscle contracts and changes length (shortens)
Ø Muscle produces enough tension (effort) to
exceed the resistance of the load being lifted
Ø E.g. contracting the bicep to lift up a book, requires
that the tension developed by the muscle exceeds
the weight of the forearm and book combined. Fig. 12.18a
Ø Uses ATP

Totora and Derrickson 2020

H) Mechanics of Body Movement
Ø Types of whole muscle contraction
2. Isometric contraction
Ø Muscle produces tension but does not change
length because tension produced is less than
required to move the load (less than
resistance)
Ø Tension increases and crossbridges form, but
Fig. 12.18b
there is no shortening
Ø E.g. trying to lift something that is too heavy, or
lifting an object and holding it in the same
position; plank position etc. Totora and Derrickson 2020
Ø Uses ATP