Animal Physiology

PS 166
Chapters 7, 8, & 20
Muscular System
Dr. Joseph Esdin

Classification of Muscles
Voluntary involuntary involuntary

Skeletal Cardiac Smooth

Striated Striated Non-striated

Voluntary Involuntary Involuntary

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 Skeletal Muscles
•  Each muscle in the body is classified as
an organ
•  A muscle is made of many fascicles
•  Fascicles are made of muscle fibers
•  Muscles fibers are made of myofibrils
•  Myofibrils are contractile proteins

Levels of Organization in
Skeletal Muscles
Fascicle
Fiber

Gastrocnemius
muscle

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 Levels of Organization in
Skeletal Muscles

Muscle fiber Dark A band Light I band

Myofibril long proteins that make up the muscle fiber

Levels of Organization in
Skeletal Muscles
•  Each myofibril is made of functional
units of contraction called sarcomeres
•  Each sarcomere is bound by a network
of interconnecting proteins called Z lines
•  Thick filaments are composed of the
contractile protein myosin

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 Levels of Organization in
Skeletal Muscles
•  The thin filaments contain the
contractile protein actin and the
regulatory proteins troponin and
tropomyosin
•  Area of the sarcomere that contain thick
filament only is called H zone

Levels of Organization in
Skeletal Muscles
•  Area of the sarcomere that contain thin
filaments only is known as I band
•  Are of the sarcomere that has an
overlap of thick and thin filaments is
called the A band

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Force production muscles is promoted by the physical interaction between the thick and thin filaments

Levels of Organization in
Skeletal Muscles
Z line A band I band

Portion
of myofibril

M line Sarcomere H zone

Thick filament A band I band
Thin filament

Cross M line Z line

bridges H zone

Myofibrils

Cross bridge

Thick filament Thin filament

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 Looking at the Filaments

Myosin Actin

Thick filament Thin filament

Thick Filaments
Actin Binding Site
ATP Binding Site

Myosin head

Myosin tail

Myosin molecules
Cross [
bridge

Thick filament

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 Thick Filaments
•  Each thick filament is made of arranged
myosin molecules
•  Each myosin molecule is made of two
heads (heavy and light chains) and two
tails (heavy chain)
•  Each myosin head contains an actin
binding site and an ATP binding site

Thin Filaments Ball is actin

black dot is myosin

•  Thin filaments are made of three

proteins
•  Actin, troponin, & tropomyosin
Regulatory proteins because they prevent the binding of the actin and myosin

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 Thin Filaments
Binding site for
attachment with
myosin cross bridge
Actin molecules

Actin helix

•  Actin is a globular protein that

polymerize to form an intertwined helix
•  Actin has a binding site for myosin

Thin Filament
+

Tropomyosin Troponin

•  Tropomyosin is arranged like a ribon

that bind the myosin binding site on the
actin

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 Thin Filament
+

Tropomyosin Troponin

•  Troponin is made of three spherical

subunits. It contains three binding site
–  _____ binding site
–  _____ binding site
–  _____ binding site

What Happens During Muscle

Contraction?

Muscle relaxed

Sarcomeres shorten

Muscle contracted

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 What Causes Binding to
Occur?
•  Two major components

Where Does ATP Come from?

Glycolysis Citric acid cycle Cytosol

Electron transport chain

Mitochondrial
Mitochondrial matrix
inner-membrane
cristae

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 Where Does Calcium Come
intracellular is the only important one.
From? Extracellucar
smooth ER
is insignificant

•  Calcium is a very important ion that has

numerous functions
•  Its high intracellular level can be toxic
and therefore must be maintained at a
very low level at all times inside the cell
(____ M)
10 ^-9 (research)

Sarcoplasmic Reticulum Is a
Modified Smooth ER
•  Lacks ribosomes
•  Contains enzymes
important for lipid
synthesis
•  Important in
metabolism of drugs
and alcohol

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 Sarcoplasmic Reticulum Is a
Modified Smooth ER
•  In muscle cells, calcium is stored in the
sarcoplasmic reticulum (SR)
•  Sarcoplasmic reticulum found around
the myofibrils
•  The lateral sacs are the end segments
that release calcium upon stimulation
•  Calcium release is triggered by series of
events

Muscle Cell
Lengthy and cylindrical

•  Muscle cells have a modified plasma

membrane known as sarcolemma
•  The sarcolemma has extensions
(invaginations) that dip deep into the
cytoplasm
•  These invaginations are known as T
tubules

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Ca is released- means that the Ca is releasted from the sarcoplasmic reticulum to the cytosol (research)
Ca found in SR, thus need ion channels(ryanodine receptors) to bring the Ca to the cytosol

Muscle Cell

Myofibrils
Segments of
sarcoplasmic
reticulum
Lateral Transverse
Sacs (TC) (T) tubule

I A band I
band band

T-Tubules & SR
•  Special voltage sensitive calcium
channels known as dihydropyridine
receptors (DHPR) are located on the T-
tubule
•  Ryanodine receptors are located on the
lateral sacs of the SR
•  Ryanodine receptors are known as foot
proteins

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Ryanodine- ligand gated channels
Ca cannot be released from the SR if ryanodine receptors are not activated
DHPR- found on the t tubules

T-Tubules & SR
Ryanodine Lateral sac
receptor of sarcoplasmic
Reticulum

T tubule

Lateral sacs Ca2+

of SR
T tubule
DHPR

What Triggers Ca Release?

Under complete command of motor neuron
Synapse is now called a neuromuscular junction
Motor neuron

Muscle fiber

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 Neuromuscular Junction

Axon terminal

Neurotransmitter Acetyl Choline

Sarcolemma

T-tubules Muscle cell

Myofibril

T-Tubules & SR
Ryanodine Lateral sac
receptor of sarcoplasmic
Reticulum

T tubule

Lateral sacs Ca2+

of SR
T tubule
DHPR

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 Neuromuscular Junction

Axon terminal

Neurotransmitter
Sarcolemma
(ACh)

Muscle cell

ACh
receptor

What Causes Ca Release?

•  Action potential at the axon terminal
stimulate the release of Acetylcholine
(ACh)
•  ACh bind to Ach receptors activating
them, causing Na entry into the cell
•  Na depolarizes the membrane
(Endplate potential)

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 What Causes Ca Release?
•  EPP cause an action potential to occur
in the muscle cell
•  The action potential travels down the
sarcolemma then dip into the T-tubules
•  The action potential activates DHPR
•  DHPR activate rayanodine receptors
which leads to Ca release

How is Ca Released?
Ryanodine Lateral sac
receptor of sarcoplasmic
Reticulum

T tubule

Lateral sacs Ca2+

of SR
T tubule
DHPR

DHPR is voltage gated, and touch the ryanodine and serve as a ligand

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 Where Does Ca Go?
•  Calcium released bind on troponin
•  Troponin, which are bound to
tropmyosin slide away from the actin
exposing the binding site of myosin
•  Myosin binds to actin

Muscle Contraction

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 Cross Bridge Cycle

ADP No Ca 2+ ADP
Pi Pi

1 Energized 2b Resting

Ca 2+ present (excitation)

ATP (Mg 2+) ADP

Pi

4a Detachment 2a Binding
Energy

Fresh ATP available

ADP
Energy
Pi
Power Stroke
3 Bending (power stroke)

Cross Bridge Cycle

•  ADP & Pi are initially bound to the cross
bridge of the the myosin (energized
state)
•  When actin is exposed, myosin binds to
actin
•  ADP & Pi unbind from the myosin head
•  Myosin head bends, pulling the actin in

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 Cross Bridge Cycle
•  ATP binds to myosin head on its
binding site, causing detachment to
occur
•  ATP is hydrolyzed to ADP & Pi which
brings the myosin head to the energized
state again

What Stops the Cycle?

•  Two major steps must happen to stop
the cross bridge cycle from occurring:
–  Removing
–  Removing

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 How Can ACh Be Removed?
•  Acetylcholine esterase breaks down
acetylcholine
•  AChE is a membrane enzyme
•  ACh is then taken back up for recycling

How Can ACh Be Removed?

Axon terminal

Neurotransmitter
Sarcolemma
(ACh)

ACh Muscle cell

esterase

ACh
receptor

Bursts of contractions- ACh is released, broken down

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 How Can Ca Be Removed?
•  Calcium is pumped back to the SR by
calcium pumps

How Can Ca Be Removed?

SR

Calcium pump

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There is a slight delay to ensure that you have all the things you need to generate force
Latency, contraction, relaxtion are all included in a single twitch
Twitch- the contraction
There is a continuous contraction that occurs when we are using our muscles for a long time

Muscle Contraction

Force production

Action potential in a
muscle fiber

Mechanics of Muscle Fiber

Contraction
•  Muscle fiber contraction is known as
muscle twitch

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 Factors That Affect Muscle
Fiber Contraction
•  Load velocity relationship
•  Length tension relationship
•  Frequency of stimulation

Maximize activity of muscle

1. How quick contraction time
2. How long it can contract
3. How much force is needed

Load- force acting on the muscle

tension- force produced by the muscle

Load-Velocity Relationship

•  The heavier the load, the slower the

velocity

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There is an optimal length of the muscle to produce the most force
A produces the most force- about 100%
There is more interaction between the thick and tin filament at A than B
The more overlap there is in the myosin and actin, the more force is produced
At rest, the body is at A
Length-Tension Relationship

•  The closer the fiber to optimal length,

the more the tension

Ca release and recruiting actin myosin

There is a ceiling effect- recruited every actin and myosin
You will run out of ATP eventually, so there is a point where contractile act falls

Frequency of Stimulation
Tetanus

Single Twitch
Twitch Summation Fatigue

^ Before it can fully relax. the stimulus is done again

•  The higher the frequency, the higher the

force

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 Skeletal Muscle Mechanics
Force is produced but the length is not changing- ie when you hold
Experiemntally only
something at the same height
•  Isometric contraction: lifting a heavy
object. Length remains the same
•  Isotonic contraction: the load is the
same but the length changes
–  Concentric: lifting an object
–  Eccentric contraction: lengthening of the
muscle while producing force
When you are changing the height of the object, the contraction is
changing but the load doesnt change

Skeletal Muscle Mechanics

Sarcomeres

Load
Triceps
Biceps

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 What Affect Skeletal Muscle
Contraction?
•  Tension produced by each muscle fiber

•  Number of fibers contracting within a

muscle

Motor Unit

•  A motor unit is Muscle

made of a fibers
neuron and all
the muscle
fibers it
innervates
•  Motor units
vary in size

One neuron can stimulate multiple muscle cells

Amuscle cell can only enervate one muscle cell

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 Motor Unit

The closer you are to the maximum moter unit recruitment, the faster you will become fatigued

Motor Unit Recruitment

Muscle with a small motor unit Muscle with a large motor unit

Number of motor units recruited Number of motor units recruited

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 Where Does the Muscle Get
the ATP From?
•  Muscle get glucose and oxygen and
use to produce energy
•  There are three sources of energy:
–  Creatine phosphate
–  Oxidative phosphorylation
Where do we need ATP
–  Glycolysis 1. Myosin head needs ATP move back and force
2. Ca pumps
3. Detachment of ATP from myosin and actin

Where Does the Muscle Get

the ATP From?

Creatine- immediate source, contains phosphate to make ATP from ADP

-Extremely quick, readily available
-But gets depleted quickly

Oxidative Phosphorylation
-Gives you a lot of ATP
-But dependent on Oxugen
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Glycolysis fermentation
-produces a lot of waste products
 What Causes Muscle
Fatigue?
•  Local increase of inorganic phosphate
•  Build up of lactic acid
•  Depletion of energy

Types of Muscle Fibers

•  Slow-oxidative: Type I fibers generates small amount of force for a long period of time
•  Fast-oxidative: Type IIa fibers generates huge amount of force, short period
•  Fast-glycolytic: Type IIb fibers Fatigue quickly

Amount of time ti takes to fatigue changes, the amount of force they can produce is different

Contraction speeds

ATP Synthesis

Recruit different muscle fibers depending on what you need

Every single muscle has a combination of these different mscle fibers

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 How Do the Types of Muscle
Fibers Differ?
•  Myosin ATPase activity 2 enxyme that converts atp to adp
•  Mitochondria 1 and 2a (both rely on oxygen)
•  Glycolytic enzyme 2b
•  Speed of contraction 2
•  Resistance to fatigue 1
•  Myoglobin 1 and 2a- stores oxygen

In Summary…
•  Muscles are anaerobic
–  Generate high output for a short period of
time
•  Muscles that are aerobic
–  Generate low output for a high period of
time

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 Muscle Adaptation
•  Flying animals and insects must have
muscles that produce high force for a
long period of time!
•  They do so by developing special
features for adaptations

Humming Bird

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 Muscle Adaptation
•  Increase in
muscle
temperature (30˚
to 40˚C causes a
2.2 fold increase
in ATP
production

When they fly, temp increases, because theyre generating more ATP
Mitochondria have more christae so they can make more ATP (high SA)

Muscle Adaptation
•  Warm up,
basking, or
shivering allow
an increase in
muscle
temperature
•  This leads to
more calcium
clearance

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 Muscle Adaptation
•  Mitochondria
contain more
cristae leading to
muscles
consuming more
O2

Asynchronous Muscle
Contraction
•  Two sets of large
antagonistic
muscles:
–  Dorsal ventral
muscles (DVM)
–  Dorsal
longitudinal
muscles (DLM)

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 Smooth Muscle

Relaxed Contracted

Dense bodies

Skeletal Vs Smooth Muscles

•  Role of the nervous system
•  Hormonal effect
•  Striation
•  Regulatory proteins
•  T-Tubules
•  Source of Calcium
•  Calcium regulation
Somatic- voluntary NS
Autonomic/sympatetic/parasympatetic- involuntary NS (regulates organs)
Hormonal Effect- hormones do not regulate skeletal muscle contraction, smooth muscles there is
Endocrine system increases muscle contraction (cortisol and epinephrine) inducling effects on contraction
Striation- sarcomeres. no sarcomeres are present in smooth muscles. actin and myosin are there
Regulatory- troponin and tropomyosin, smooth muscles have very little troponin and tropomyosin
T-Tubules- Folds of the muscle cell, absent in smooth muscles
Source of Calcium- comes from SR in skeletal, extracelluar in smooth muscle is more important 35
calmodulin
 Smooth Muscle Contraction
•  Calcium binds to calmodulin forming
Ca-Calm complex
•  This complex activates myosin light
chain kinase (MLCK)
•  MLCK phosphorylates the myosin head
and causes attachment
•  Detachments is achieved by myosin
light chain phosphotase

Smooth Muscle Contraction

Calmodulin activation is Ca dependent
Ca2+ Ca Calmodulin complex acts on MLCK
-High Ca activates MLCK
Calmodulin Ca2+ -calmodulin -phosphorylates myosin head
Phosphorylated myosin- forms a different cross bridge cycle

Inactive MLCK Active MLCK

ATP
Pi
ADP

Inactive myosin Phosphorylated myosin

(can bind with actin)

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 Smooth Muscle Contraction

Types of Smooth Muscles

Located around organs

•  Single-unit smooth muscle Entire muscle organ contracts continuously

•  Multiunit smooth muscle Only some parts of the muscles contract

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 Single-Unit Smooth Muscles
•  Digestive, reproductive, urinary tracts
•  Electrically coupled through gap junctions
•  No gradation
•  Muscle tone never completes relaxed, low calcium
•  Spontaneous activity of action potential: yes myogenic

Multi-Unit Smooth Muscles

Large
•  Blood vessels, airways, eyes, hair
follicles
•  Neurogenic
•  No gap junctions
•  Gradation
•  No muscle tone

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