MUSCLE PHYSIOLOGY - Sinoe Medical Association

MUSCLE PHYSIOLOGY Skeletal Muscle Contraction

• In order to contract, a skeletal muscle
must:

– Be stimulated by a nerve ending
– Propagate an electrical current, or action

potential, along its sarcolemma
– Have a rise in intracellular Ca2+ levels, the

final trigger for contraction

• Linking the electrical signal to the
contraction is excitation-contraction
coupling

Sliding Filament Model of Nerve Stimulus of Skeletal
Contraction Muscle

• Each myosin head binds and detaches • Skeletal muscles are stimulated by motor
several times during contraction, acting like neurons of the somatic nervous system
a ratchet to generate tension and propel
the thin filaments to the center of the • Axons of these neurons travel in nerves to
sarcomere muscle cells

• As this event occurs throughout the • Axons of motor neurons branch profusely
sarcomeres, the muscle shortens as they enter muscles

• Each axonal branch forms a
neuromuscular junction with a single
muscle fiber

1

Neuromuscular Junction Neuromuscular Junction

• The neuromuscular junction is formed Figure 9.7 (a-c)
from:

– Axonal endings, which have small
membranous sacs (synaptic vesicles) that
contain the neurotransmitter acetylcholine
(ACh)

– The motor end plate of a muscle, which is a
specific part of the sarcolemma that contains
ACh receptors and helps form the
neuromuscular junction

Neuromuscular Junction Neuromuscular Junction

• Though exceedingly close, axonal ends and • When a nerve impulse reaches the end of
muscle fibers are always separated by a space an axon at the neuromuscular junction:
called the synaptic cleft
– Voltage-regulated calcium channels open and
allow Ca2+ to enter the axon

– Ca2+ inside the axon terminal causes axonal
vesicles to fuse with the axonal membrane

PLAY InterActive Physiology ®:
The Neuromuscular Junction, pages 3-5

2

Neuromuscular Junction Action Potential

– This fusion releases ACh into the synaptic • A transient depolarization event that
cleft via exocytosis includes polarity reversal of a sarcolemma
(or nerve cell membrane) and the
– ACh diffuses across the synaptic cleft to ACh propagation of an action potential along the
receptors on the sarcolemma membrane

– Binding of ACh to its receptors initiates an
action potential in the muscle

Destruction of Acetylcholine Role of Acetylcholine (Ach)

• ACh bound to ACh receptors is quickly • ACh binds its receptors at the motor end
destroyed by the enzyme plate
acetylcholinesterase
• Binding opens chemically (ligand) gated
• This destruction prevents continued muscle channels
fiber contraction in the absence of
additional stimuli • Na+ and K+ diffuse out and the interior of
the sarcolemma becomes less negative

• This event is called depolarization

PLAY InterActive Physiology ®:
The Neuromuscular Junction, pages 6-10

3

Action Potential: Electrical

Depolarization Conditions of a Polarized

• Initially, this is a local electrical event called • The predominSanatrcolemma
end plate potential
extracellular ion is
• Later, it ignites an action potential that Na+
spreads in all directions across the
sarcolemma • The predominant
intracellular ion is
K+

• The sarcolemma is Figure 9.8a
relatively
impermeable to
both ions

Action Potential: Electrical Action Potential: Depolarization
Conditions of a Polarized and Generation of the Action
• The outside Sarcolemma Potential

(extracellular) face is • An axonal terminal of
positive, while the a motor neuron
inside face is releases ACh and
negative causes a patch of the
• This difference in sarcolemma to
charge is the resting become permeable
membrane potential to Na+ (sodium
channels open)
Figure 9.8a
Figure 9.8b

4

Action Potential: Depolarization Action Potential: Propagation of
and Generation of the Action
the Action Potential
• Na+ enters the cPello, tential
• Thus, the action
and the resting potential travels
potential is rapidly along the
decreased sarcolemma
(depolarization
occurs) • Once initiated, the
action potential is
• If the stimulus is unstoppable, and
strong enough, an ultimately results in
action potential is the contraction of a
initiated muscle

Figure 9.8b Figure 9.8c

Action Potential: Propagation of Action Potential: Repolarization
the Action Potential
• Immediately after the
• Polarity reversal of depolarization wave passes, the
the initial patch of sarcolemma permeability
sarcolemma changes changes
the permeability of
the adjacent patch • Na+ channels close and K+
channels open
• Voltage-regulated
Na+ channels now • K+ diffuses from the cell,
open in the adjacent restoring the electrical polarity of
patch causing it to the sarcolemma
depolarize
Figure 9.8d
Figure 9.8c

5

Action Potential: Repolarization Excitation-Contraction Coupling

• Repolarization occurs in the same • Myosin cross bridges alternately attach and
direction as depolarization, and detach
must occur before the muscle can
be stimulated again (refractory • Thin filaments move toward the center of
period) the sarcomere

• The ionic concentration of the • Hydrolysis of ATP powers this cycling
resting state is restored by the process
Na+-K+ pump
• Ca2+ is removed into the SR, tropomyosin
Figure 9.8d blockage is restored, and the muscle fiber
relaxes

Excitation-Contraction Coupling Action Potential Scan

• Once generated, the action potential: Figure 9.9

– Is propagated along the sarcolemma
– Travels down the T tubules
– Triggers Ca2+ release from terminal cisternae

• Ca2+ binds to troponin and causes:

– The blocking action of tropomyosin to cease
– Actin active binding sites to be exposed

6

Excitation-Contraction (EC) Axon terminal Neurotransmitter released diffuses
Coupling across the synaptic cleft and attaches
Synaptic to ACh receptors on the sarcolemma.
1. Action potential generated and cleft
propagated along sarcomere to Synaptic
T-tubules vesicle

2. Action potential triggers Ca2+ ACh ACh ACh
release
Figure 9.10
3. Ca++ bind to troponin; blocking
action of tropomyosin released

4. contraction via crossbridge
formation; ATP hyrdolysis

5. Removal of Ca+2 by active
transport

6. tropomyosin blockage restored;
contraction ends

Figure 9.10

Axon terminal Neurotransmitter released diffuses Axon terminal Neurotransmitter released diffuses
across the synaptic cleft and attaches across the synaptic cleft and attaches

to ACh receptors on the sarcolemma. to ACh receptors on the sarcolemma.

Synaptic Synaptic

Synaptic cleft Synaptic cleft
vesicle vesicle
Sarcolemma Sarcolemma

T tubule T tubule

ACh ACh ACh 1 Net entry of Na+ Initiates ACh ACh ACh 1 Net entry of Na+ Initiates
an action potential which an action potential which
is propagated along the is propagated along the
sarcolemma and down sarcolemma and down
the T tubules. the T tubules.

Ca2+ Ca2+
Ca2+
SR tubules (cut)

SR

2 Action potential in Ca2+

T tubule activates Ca2+
Ca2+
ADP voltage-sensitive receptors,
Pi which in turn trigger Ca2+

release from terminal

cisternae of SR Ca2+ Ca2+
into cytosol.

6 Tropomyosin blockage restored, Ca2+
blocking myosin binding sites on
3 Calcium ions bind to troponin;
actin; contraction ends and troponin changes shape, removing
the blocking action of tropomyosin;
muscle fiber relaxes. actin active sites exposed.

5 Removal of Ca2+ by active transport 4 Contraction; myosin heads alternately attach to
into the SR after the action actin and detach, pulling the actin filaments toward
potential ends. the center of the sarcomere; release of energy by
ATP hydrolysis powers the cycling process.
Ca2+

Figure 9.10 Figure 9.10

7

Axon terminal Neurotransmitter released diffuses Axon terminal Neurotransmitter released diffuses
across the synaptic cleft and attaches across the synaptic cleft and attaches

to ACh receptors on the sarcolemma. to ACh receptors on the sarcolemma.

Synaptic Synaptic

Synaptic cleft Synaptic cleft
vesicle vesicle
Sarcolemma Sarcolemma

T tubule T tubule

ACh ACh ACh 1 Net entry of Na+ Initiates ACh ACh ACh 1 Net entry of Na+ Initiates
an action potential which an action potential which
is propagated along the is propagated along the
sarcolemma and down sarcolemma and down
the T tubules. the T tubules.

Ca2+ Ca2+ Ca2+ Ca2+
Ca2+ Ca2+
SR tubules (cut) SR tubules (cut)

SR SR

2 Action potential in Ca2+ 2 Action potential in Ca2+
Ca2+ Ca2+
T tubule activates T tubule activates

voltage-sensitive receptors, voltage-sensitive receptors,
which in turn trigger Ca2+ which in turn trigger Ca2+

release from terminal release from terminal

cisternae of SR Ca2+ Ca2+ cisternae of SR Ca2+ Ca2+
into cytosol. into cytosol.

Ca2+ Ca2+

Ca2+ 3 Calcium ions bind to troponin;
troponin changes shape, removing
the blocking action of tropomyosin;
actin active sites exposed.

4 Contraction; myosin heads alternately attach to
actin and detach, pulling the actin filaments toward
the center of the sarcomere; release of energy by
ATP hydrolysis powers the cycling process.

Figure 9.10 Figure 9.10

Axon terminal Neurotransmitter released diffuses Axon terminal Neurotransmitter released diffuses
across the synaptic cleft and attaches across the synaptic cleft and attaches

to ACh receptors on the sarcolemma. to ACh receptors on the sarcolemma.

Synaptic Synaptic

Synaptic cleft Synaptic cleft
vesicle vesicle
Sarcolemma Sarcolemma

T tubule T tubule

ACh ACh ACh 1 Net entry of Na+ Initiates ACh ACh ACh 1 Net entry of Na+ Initiates
an action potential which an action potential which
is propagated along the is propagated along the
sarcolemma and down sarcolemma and down
the T tubules. the T tubules.

Ca2+ Ca2+ Ca2+ Ca2+
Ca2+ Ca2+
SR tubules (cut) SR tubules (cut)

SR SR

2 Action potential in Ca2+ 2 Action potential in Ca2+
Ca2+ Ca2+
T tubule activates T tubule activates

voltage-sensitive receptors, voltage-sensitive receptors,
which in turn trigger Ca2+ which in turn trigger Ca2+

release from terminal release from terminal

cisternae of SR Ca2+ Ca2+ cisternae of SR Ca2+ Ca2+
into cytosol. into cytosol.

Ca2+ Ca2+

Ca2+ 3 Calcium ions bind to troponin; Ca2+ 3 Calcium ions bind to troponin;
troponin changes shape, removing troponin changes shape, removing
the blocking action of tropomyosin; the blocking action of tropomyosin;
actin active sites exposed. actin active sites exposed.

5 Removal of Ca2+ by active transport 4 Contraction; myosin heads alternately attach to
into the SR after the action actin and detach, pulling the actin filaments toward
potential ends. the center of the sarcomere; release of energy by
ATP hydrolysis powers the cycling process.
Ca2+

Figure 9.10 Figure 9.10

8

Axon terminal Neurotransmitter released diffuses Role of Ionic Calcium (Ca2+) in
across the synaptic cleft and attaches
the Contraction Mechanism
to ACh receptors on the sarcolemma.
• At higher intracellular
Synaptic Ca2+ concentrations:

Synaptic cleft – Additional calcium
vesicle binds to troponin
Sarcolemma (inactive troponin
binds two Ca2+)
T tubule
– Calcium-activated
ACh ACh ACh 1 Net entry of Na+ Initiates troponin binds an
an action potential which additional two Ca2+
is propagated along the at a separate
sarcolemma and down regulatory site
the T tubules.
Figure 9.11b
Ca2+ Ca2+
Ca2+
SR tubules (cut)

SR

2 Action potential in Ca2+

T tubule activates Ca2+
Ca2+
ADP voltage-sensitive receptors,
Pi which in turn trigger Ca2+

release from terminal

cisternae of SR Ca2+ Ca2+
into cytosol.

6 Tropomyosin blockage restored, Ca2+
blocking myosin binding sites on
3 Calcium ions bind to troponin;
actin; contraction ends and troponin changes shape, removing
the blocking action of tropomyosin;
muscle fiber relaxes. actin active sites exposed.

5 Removal of Ca2+ by active transport 4 Contraction; myosin heads alternately attach to
into the SR after the action actin and detach, pulling the actin filaments toward
potential ends. the center of the sarcomere; release of energy by
ATP hydrolysis powers the cycling process.
Ca2+

Figure 9.10

Role of Ionic Calcium (Ca2+) in Role of Ionic Calcium (Ca2+) in
the Contraction Mechanism the Contraction Mechanism

• At low intracellular • Calcium-activated
Ca2+ concentration: troponin undergoes a
conformational
– Tropomyosin blocks change
the binding sites on
actin • This change moves
tropomyosin away
– Myosin cross bridges from actin’s binding
cannot attach to sites
binding sites on actin
Figure 9.11c
– The relaxed state of
the muscle is
enforced

Figure 9.11a

9

Role of Ionic Calcium (Ca2+) in Myosin head ADP
the Contraction Mechanism (high-energy Pi
configuration)
• Myosin head can
now bind and cycle 1 Myosin head attaches to the actin
myofilament, forming a cross bridge.
• This permits
contraction (sliding of Thin filament
the thin filaments by
the myosin cross ADP Thick filament ADP
bridges) to begin Pi
ATP
Figure 9.11d hydrolysis

4 As ATP is split into ADP and Pi, the myosin 2 Inorganic phosphate (Pi) generated in the
head is energized (cocked into the high-energy previous contraction cycle is released, initiating

conformation). the power (working) stroke. The myosin head
pivots and bends as it pulls on the actin filament,

sliding it toward the M line. Then ADP is released.

ATP

ATP Myosin head
(low-energy
configuration)

3 As new ATP attaches to the myosin head, the link between
myosin and actin weakens, and the cross bridge detaches.

Figure 9.12

Sequential Events of Myosin head ADP
(high-energy Pi
Contraction configuration)

• Cross bridge formation – myosin cross 1 Myosin head attaches to the actin
bridge attaches to actin filament myofilament, forming a cross bridge.

• Working (power) stroke – myosin head Figure 9.12
pivots and pulls actin filament toward M
line 10

• Cross bridge detachment – ATP attaches
to myosin head and the cross bridge
detaches

• “Cocking” of the myosin head – energy
from hydrolysis of ATP cocks the myosin

PLAY InterActive Physiology ®: Sliding Filament Theory, pages 3-29

head into the high-energy state

Myosin head ADP Myosin head ADP
(high-energy Pi (high-energy Pi
configuration) configuration)

1 Myosin head attaches to the actin 1 Myosin head attaches to the actin
myofilament, forming a cross bridge. myofilament, forming a cross bridge.

ADP ADP

2 Inorganic phosphate (Pi) generated in the 2 Inorganic phosphate (Pi) generated in the
previous contraction cycle is released, initiating previous contraction cycle is released, initiating
the power (working) stroke. The myosin head
pivots and bends as it pulls on the actin filament, the power (working) stroke. The myosin head
sliding it toward the M line. Then ADP is released. pivots and bends as it pulls on the actin filament,

sliding it toward the M line. Then ADP is released.

ATP

ATP Myosin head
(low-energy
configuration)

3 As new ATP attaches to the myosin head, the link between
myosin and actin weakens, and the cross bridge detaches.

Figure 9.12 Figure 9.12

Myosin head ADP Myosin head ADP
(high-energy Pi (high-energy Pi
configuration) configuration)

1 Myosin head attaches to the actin 1 Myosin head attaches to the actin
myofilament, forming a cross bridge. myofilament, forming a cross bridge.

Thin filament

ADP ADP Thick filament ADP
Pi
2 Inorganic phosphate (Pi) generated in the ATP
previous contraction cycle is released, initiating hydrolysis
the power (working) stroke. The myosin head
pivots and bends as it pulls on the actin filament, 4 As ATP is split into ADP and Pi, the myosin 2 Inorganic phosphate (Pi) generated in the
sliding it toward the M line. Then ADP is released. head is energized (cocked into the high-energy previous contraction cycle is released, initiating

ATP conformation). the power (working) stroke. The myosin head
pivots and bends as it pulls on the actin filament,

sliding it toward the M line. Then ADP is released.

ATP

ATP Myosin head
(low-energy
configuration)

3 As new ATP attaches to the myosin head, the link between
myosin and actin weakens, and the cross bridge detaches.

Figure 9.12 Figure 9.12

11

Myosin head ADP Contraction of Skeletal Muscle
(high-energy Pi (Organ Level)
configuration)
• Contraction of muscle fibers (cells) and
1 Myosin head attaches to the actin muscles (organs) is similar
myofilament, forming a cross bridge.
• The two types of muscle contractions are:
Thin filament
– Isometric contraction – increasing muscle
ADP Thick filament ADP tension (muscle does not shorten during
Pi contraction)
ATP
hydrolysis – Isotonic contraction – decreasing muscle
length (muscle shortens during contraction)
4 As ATP is split into ADP and Pi, the myosin 2 Inorganic phosphate (Pi) generated in the
head is energized (cocked into the high-energy previous contraction cycle is released, initiating

conformation). the power (working) stroke. The myosin head
pivots and bends as it pulls on the actin filament,

sliding it toward the M line. Then ADP is released.

ATP

ATP Myosin head
(low-energy
configuration)

3 As new ATP attaches to the myosin head, the link between
myosin and actin weakens, and the cross bridge detaches.

Figure 9.12

Contraction of Skeletal Muscle Motor Unit: The Nerve-Muscle
Fibers Functional Unit

• Contraction – refers to the activation of • A motor unit is a motor neuron and all the
myosin’s cross bridges (force-generating muscle fibers it supplies
sites)
• The number of muscle fibers per motor unit
• Shortening occurs when the tension can vary from four to several hundred
generated by the cross bridge exceeds
forces opposing shortening • Muscles that control fine movements
(fingers, eyes) have small motor units
• Contraction ends when cross bridges
become inactive, the tension generated
declines, and relaxation is induced

12

Motor Unit: The Nerve-Muscle Muscle Twitch
Functional Unit
• A muscle twitch is the response of a
muscle to a single, brief threshold stimulus

• There are three phases to a muscle twitch

– Latent period
– Period of contraction
– Period of relaxation

PLAY InterActive Physiology ®:
Contraction of Motor Units, pages 3-9

Figure 9.13a

Motor Unit: The Nerve-Muscle Phases of a Muscle Twitch
Functional Unit
• Latent period – first
• Large weight-bearing muscles (thighs, few msec after
hips) have large motor units stimulus; EC
coupling taking place
• Muscle fibers from a motor unit are spread
throughout the muscle; therefore, • Period of contraction
contraction of a single motor unit causes – cross bridges from;
weak contraction of the entire muscle muscle shortens

• Period of relaxation – Figure 9.14a
Ca2+ reabsorbed;
muscle tension goes
t

13

Muscle Twitch Comparisons Muscle Response to Varying
• A single stimulus Sretsiumltsuilni a single

contractile response – a muscle twitch

• Frequently delivered stimuli (muscle does
not have time to completely relax)
increases contractile force – wave
summation

Figure 9.14b Figure 9.15

Graded Muscle Responses Muscle Response to Varying
Stimuli
• Graded muscle responses are:
• More rapidly delivered stimuli result in
– Variations in the degree of muscle contraction incomplete tetanus
– Required for proper control of skeletal
• If stimuli are given quickly enough,
movement complete tetanus results

• Responses are graded by: Figure 9.15

– Changing the frequency of stimulation
– Changing the strength of the stimulus

14

Muscle Response: Stimulation Size Principle

Strength Figure 9.17

• Threshold stimulus – the stimulus strength
at which the first observable muscle
contraction occurs

• Beyond threshold, muscle contracts more
vigorously as stimulus strength is
increased

• Force of contraction is precisely controlled
by multiple motor unit summation

• This phenomenon, called recruitment,
brings more and more muscle fibers into
play

Stimulus Intensity and Muscle Treppe: The Staircase Effect
Tension
• Staircase – increased contraction in
Figure 9.16 response to multiple stimuli of the same
strength

• Contractions increase because:

– There is increasing availability of Ca2+ in the
sarcoplasm

– Muscle enzyme systems become more
efficient because heat is increased as muscle
contracts

15

Treppe: The Staircase Effect Contraction

• Each myofiber contains myofilaments.

– Thick filaments: MYOSIN
– Thin filaments: ACTIN

Figure 9.18

• How do STRIATED muscles contract? SARCOMERE

•Many in each striated myofiber
•Sarcomere:

–Z disc to Z disc.

16

SARCOMERE Muscle Contraction

Muscle Contraction

17

Muscle Contraction Muscle Contraction

•Sliding filament theory of contraction. • Many sarcomeres are present in each myofiber.

•Muscle contracts: • Muscle contracts:
–myosin (thick) filaments slide towards center • Each sarcomere gets shorter.
of sarcomere, along actin (thin filaments).

•Note: Cross bridges are part of the myosin
proteins that extend out toward actin.

Sliding Filament Theory of Sliding Filament Theory of
Contraction Contraction

18

• How does the sliding happen? Myosin cycle

• Myosin binding ATP which splits to ADP and
Pi.

• Myosin heads attach to actin.
• Pi is released, causing the power stroke to

occur.
• Power stroke pulls actin filament.
• ADP is released, because myosin binds to a

new ATP, and releases from the actin.

Myosin Myosin cycle

•Myosin is an ATPase (and motor protein).

•Each myosin head contains an ATP-binding
site AND an actin binding site.

19

• How is the contraction regulated? Regulation

• Ca2+ influx releases
troponin/tropomyosin block -> muscle
contracts!

Regulation Regulation

• ATP is present, so contractions would be
continuous

• BUT

– Tropomyosin lies along actin filament
– Troponin is attached to tropomyosin.

• Tropomyosin is in the way, myosin can’t bind to
actin.

20

Regulation Excitation-Contraction Coupling

-- Axon of motor neuron produces AP in
sarcolemma of myofiber.
•- APs travel down sarcolemma and T tubules.
-- SR terminal cisternae releases Ca2+

-- sarcomeres contract!

What’s upstream of the Ca2+ influx? Muscle Relaxation

• Ca2+ pumped back into SR through
Ca2+-ATPase pumps (always on).

• End of neuronal stimulation:

– ACh-esterase degrades ACh.
– Ca2+ channels close.
– Choline recycled to make more ACh.

21

Sliding Filament Neural Control

• ATP is energy when split into ADP+P. • Motor unit is one nerve and all fibers it
• Electrical impulse (action potential) travels down innervates.

the nerve and into T-tubules. • 1:1 or 1:1,000.
• Depolarization occurs (sodium and potassium • Large and small, fast and slow.
• Fibers may lie scattered throughout the muscle
exchange). Local and millisecond time lapse.
• AP stimulates the release of calcium. and not all together.
• Calcium binds to troponin. • Fiber diameter is related to work performed
• Actin and myosin then combine.
(hypertrophy?).
• When one fiber is activated all fibers are

activated.

Sliding Filament cont… Muscle Structure

• Rigor of muscle upon death? • Muscle fibers are long
• Cross bridge cycle occurs. • Diameter of a hair
• Nerve impulse stops. • Grouped in bundles (fasciculi)
• No calcium influx. • Neuromuscular junction
• Allowing troponin to attach and inhibit • Sarcoplasm contains fibers
• Hundreds to thousands of myofibrils
actin-myosin attachment.

22

Muscle Structure cont…

• Myofibrils contains protein myofilaments
• Actin and myosin
• Crossbridges protrude from myosin
• Arranged longitudinally in sarcomere
• From Z-line to Z-line
• Surrounded by sarcoplasmic reticulum

23

Contractile proteins actin, Resting Phase
myosin, troponin, and
tropomyosin • Little calcium in the myofibril
• Calcium stored in sarcoplasmic reticulum
• Very few crossbridges attached
• No tension in muscle

Sliding Filament Theory Excitation-Coupling Phase

• Actin slides forward on myosin filaments • Calcium influx
• Shortening the sarcomere • Calcium binds with troponin
• Many must shorten for movement • Troponin is on actin filaments
• Rapid repeated contractions take place • Tropomyosin shifts
• Myosin crossbridge attaches to actin

24

Contraction Phase

• Energy from hydrolysis of ATP
• Catalyzed by ATPase
• Another ATP to detach crossbridge
• Thus contraction continues
• Exhaustion of ATP, ATPase and calcium

Recharge Phase

• Muscle shortening
• Crossbridges work in cycle
• Relax when AP stops
• Calcium returns to sarcoplasmic reticulum

(ATP for pump)

25

Types of Muscle Action Cross Sectional Area (CSA)

• Concentric – shortening • Maximum force is related to CSA
• Eccentric – lengthening (20% greater than • Larger CSA equals larger force
• Sarcomeres must be parallel
concentric with less energy) • More potential crossbridges
• Isometric – no change in length • Thicker muscles apply force

Force Production Velocity of Shortening

• Number of crossbridges dictates force • Sarcomeres in series increase velocity
• Amount of calcium regulates crossbridge • Sarcomeres shorten simultaneously
• Longer muscles produce velocity
cycle • Force production is inversely related to
• Increased frequency of AP
• Number of active motor units velocity
• Increased force • Fewer crossbridges in contact
• Pennation angle affects force and velocity
– Frequency of stimulation
– More motor units

26

Length-Tension Relationship DOMS

• Potential crossbridges depends on muscle • Occurs 24-72 hours post exercise
length • Muscle damage leads to inflammation
• Increase in muscle fluid
• Percentage of contraction • Reduces strength
• Long or short reduces force • Reduces oxidative process
• Resting length is optimal

Stretch-Shortening Cycle Older Muscle

• Pre stretch of muscle • Sarcopenia is loss of muscle mass
• Concentric preceded by eccentric • Older adults especially
• Force is increased • Pronounced in lower limb extensors
• Stretch reflex potentiation • Predominately type II fibers
• Elastic energy • Inactivity related

27

Concentric and eccentric.

Max Power

Torque 750 d/s

Force

Min
0 240

28

Muscle velocity is proportional to muscle fiber length.

The first measurable effect is an increase in the neural drive stimulating
muscle contraction.

Muscle force is proportional to physiologic
cross-sectional area (PCSA). (mass?)

Hypertrophy results primarily from the growth of each muscle cell,
rather than an increase in the number of cells.

29

Muscle fiber types are The three primary fiber
classified by types in human skeletal
• Slow twitch omxiudasticvele(SO)
• Anatomical appearance: red versus white
• Fast twitch oxidative glycolytic
• Muscle function: fast-slow or fatigable (FOG)
versus fatigue resistant
• Fast twitch glycolytic (FG)
• Biochemical properties: such as high or low
aerobic capacity

• Histochemical properties: such as enzyme
profile

Characteristics of the Characteristics of muscle
structure of skeletal muscle fiber types

• The muscle is made up of long,
cylindrical fibers.

• Each fiber is a large cell with up to
several hundred nuclei.

• Each cell is structurally independent of
its neighboring fiber or cell.

• The muscle has cross-striations of
alternating light and dark bands.

30

Structure of the myofibril Series of events that lead to muscle

• Sarcomere contraction in the sliding filament model
– functional unit
– composed of two types of parallel myofilaments Contraction

• Myosin 1. Neural stimulation causes the
• Actin sarcoplasmic reticulum to
release calcium.
• Z-line
– membrane that separates sarcomeres 2. Calcium binds to troponin,
which removes the inhibitory
• A band effect of tropomyosin and
– dark band seen as part of striation actin-myosin bind.

• H zone 3. Myosin cross-bridges swivel,
– amount by which the two ends of the thin filaments pulling the actin and z-lines.
fail to meet
4. Fresh ATP binds to the
• I band myosin cross-bridges, leading
– area between the ends of the myosin to cross-bridge recycling.
– light band in the striation
5. Neural stimulation ceases and
relaxation occurs.

Significance of fiber-type Theory 1
composition for athletes 1. Actin-myosin bind
Activates myosin ATPase
• High percentage of SO fibers—candidate Breakdown of ATP molecule
for distance running or other endurance liberates energy
sports
2. Energy causes myosin cross-
• High percentage of FT fibers—candidate bridge to swivel to center of
for power or sprint events sarcomere Myosin is bound to
actin, which is bound to Z-lines
• Percentage is genetically determined Z-lines pulled closer together
Sarcomere shortened

3. Fresh ATP molecule binds to
myosin cross-bridge
Actin-myosin binding released
Myosin cross-bridge stands
back up

4. Actin-myosin rebinds at new
site
Activates myosin ATPase
Breakdown of ATP molecule
liberates energy

5. And process repeats

31

Theory 2 Next Class

1. Myosin cross-bridge stores energy • Collect velocity spectrum data
from breakdown of ATP by myosin • Make Excel graphs of force/velocity and
ATPase Actin-myosin binding
releases stored energy power/velocity curves

2. Causes myosin cross-bridge to
swivel ADP and Pi are released
from the myosin cross-bridge

3. Fresh ATP molecule binds to
myosin cross-bridge Actin-myosin
binding released ATP is broken
down and energy causes myosin
cross-bridge to stand back up (re-
energized)

4. Fresh ATP molecule is broken
down Energy reenergizes myosin
cross-bridge

5. Process repeats

Comparing the two theories Muscle Tone

• Both theories state that fresh ATP binds to • Muscle tone:
the myosin cross-bridge to release it from
actin during cross-bridge recycling. – Is the constant, slightly contracted state of all
muscles, which does not produce active
• Theory 2 states that after the myosin-actin movements
binding is released, the fresh ATP molecule
is broken down and the energy released is – Keeps the muscles firm, healthy, and ready to
used to reenergize the myosin cross-bridge. respond to stimulus

• According to Theory 1, energy is not needed • Spinal reflexes account for muscle tone by:
to cause the myosin cross-bridge to stand
back up. – Activating one motor unit and then another

– Responding to activation of stretch receptors
in muscles and tendons

32

Isotonic Contractions Isometric Contractions

• In isotonic contractions, the muscle • Tension increases to the muscle’s
changes in length (decreasing the angle of capacity, but the muscle neither shortens
the joint) and moves the load nor lengthens

• The two types of isotonic contractions are • Occurs if the load is greater than the
concentric and eccentric tension the muscle is able to develop

– Concentric contractions – the muscle
shortens and does work

– Eccentric contractions – the muscle contracts
as it lengthens

Isotonic Contractions Isometric Contractions

Figure 9.19a Figure 9.19b

33

Muscle Metabolism: Energy for Muscle Metabolism: Anaerobic
Contraction Glycolysis

• ATP is the only source used directly for • When muscle contractile activity reaches
contractile activity 70% of maximum:

• As soon as available stores of ATP are – Bulging muscles compress blood vessels
hydrolyzed (4-6 seconds), they are – Oxygen delivery is impaired
regenerated by: – Pyruvic acid is converted into lactic acid

– The interaction of ADP with creatine
phosphate (CP)

– Anaerobic glycolysis
– Aerobic respiration

Muscle Metabolism: Energy for Muscle Metabolism: Anaerobic
Contraction Glycolysis

• The lactic acid:

– Diffuses into the bloodstream
– Is picked up and used as fuel by the liver,

kidneys, and heart
– Is converted back into pyruvic acid by the liver

Figure 9.20

34

Muscle Fatigue Oxygen Debt

• Muscle fatigue – the muscle is in a state of • Vigorous exercise causes dramatic
physiological inability to contract changes in muscle chemistry

• Muscle fatigue occurs when: • For a muscle to return to a resting state:

– ATP production fails to keep pace with ATP – Oxygen reserves must be replenished
use – Lactic acid must be converted to pyruvic acid
– Glycogen stores must be replaced
– There is a relative deficit of ATP, causing – ATP and CP reserves must be resynthesized
contractures

– Lactic acid accumulates in the muscle
– Ionic imbalances are present

Muscle Fatigue Oxygen Debt

• Intense exercise produces rapid muscle • Oxygen debt – the extra amount of O2
fatigue (with rapid recovery) needed for the above restorative processes

• Na+-K+ pumps cannot restore ionic
balances quickly enough

• Low-intensity exercise produces slow-
developing fatigue

• SR is damaged and Ca2+ regulation is
disrupted

35

Heat Production During Muscle Force of Muscle Contraction
Activity
Figure 9.21a–c
• Only 40% of the energy released in muscle
activity is useful as work

• The remaining 60% is given off as heat

• Dangerous heat levels are prevented by
radiation of heat from the skin and
sweating

Force of Muscle Contraction Length Tension Relationships

• The force of contraction is affected by: Figure 9.22

– The number of muscle fibers contracting –
the more motor fibers in a muscle, the
stronger the contraction

– The relative size of the muscle – the bulkier
the muscle, the greater its strength

– Degree of muscle stretch – muscles contract
strongest when muscle fibers are 80-120% of
their normal resting length

36

Muscle Fiber Type: Speed of
Contraction

• Slow oxidative fibers contract slowly, have
slow acting myosin ATPases, and are
fatigue resistant

• Fast oxidative fibers contract quickly, have
fast myosin ATPases, and have moderate
resistance to fatigue

• Fast glycolytic fibers contract quickly, have
fast myosin ATPases, and are easily

fatiguedPLAY InterActive Physiology ®:
Muscle Metabolism, pages 24-29

Table 9.2

Muscle Fiber Type: Functional Load and Contraction
Characteristics
Figure 9.23
• Speed of contraction – determined by
speed in which ATPases split ATP

– The two types of fibers are slow and fast

• ATP-forming pathways

– Oxidative fibers – use aerobic pathways
– Glycolytic fibers – use anaerobic glycolysis

• These two criteria define three categories –
slow oxidative fibers, fast oxidative fibers,
and fast glycolytic fibers

PLAY InterActive Physiology ®:
Muscle Metabolism, pages 16-22

37

Effects of Aerobic Exercise Proportion and Organization of Myofilaments in Smooth Muscle

• Aerobic exercise results in an increase of:

– Muscle capillaries
– Number of mitochondria
– Myoglobin synthesis

Figure 9.26

Effects of Resistance Exercise Contraction of Smooth Muscle

• Resistance exercise (typically anaerobic) • Whole sheets of smooth muscle exhibit
results in: slow, synchronized contraction

– Muscle hypertrophy • They contract in unison, reflecting their
– Increased mitochondria, myofilaments, and electrical coupling with gap junctions

glycogen stores • Action potentials are transmitted from cell
to cell

38

Contraction of Smooth Muscle Role of Calcium Ion

• Some smooth muscle cells: • Ca2+ binds to calmodulin and activates it
• Activated calmodulin activates the kinase
– Act as pacemakers and set the contractile
pace for whole sheets of muscle enzyme
• Activated kinase transfers phosphate from
– Are self-excitatory and depolarize without
external stimuli ATP to myosin cross bridges
• Phosphorylated cross bridges interact with

actin to produce shortening
• Smooth muscle relaxes when intracellular

Ca2+ levels drop

Contraction Mechanism Special Features of Smooth
Muscle Contraction
• Actin and myosin interact according to the
sliding filament mechanism • Unique characteristics of smooth muscle
include:
• The final trigger for contractions is a rise in
intracellular Ca2+ – Smooth muscle tone
– Slow, prolonged contractile activity
• Ca2+ is released from the SR and from the – Low energy requirements
extracellular space – Response to stretch

• Ca2+ interacts with calmodulin and myosin
light chain kinase to activate myosin

39

Response to Stretch Excitation

• Smooth muscle exhibits a phenomenon • All cells have a voltage difference across their
called plasma membrane. This is the result of several
stress-relaxation response in which: things:

– Smooth muscle responds to stretch only 1. The ECF is very high in Na+ while the ICF is very high in K+.
briefly, and then adapts to its new length 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,
– The new length, however, retains its ability to positive charge is constantly leaking out of the cell.
contract

– This enables organs such as the stomach and
bladder to temporarily store contents

Sliding Filaments Excitation

• All the sarcomeres in a fiber will contract 2. The Na+/K+ pump is constantly pumping 3 Na+ ions out and 2 K+
together. This contracts the fiber itself. The ions in for every ATP used. Thus more positive charge is
number of fibers contracting will determine the leaving than entering.
force of the contraction of the whole muscle.
3. There are protein anions (i.e., negatively charged proteins)
• We can actually divide the whole process of within the ICF that cannot travel through the PM.
muscle contraction into 4 steps:
• What this adds up to is the fact that the inside of the cell is negative
– Excitation with respect to the outside. The interior has less positive charge
– Excitation-contraction coupling than the exterior.
– Contraction
– Relaxation

40

Excitation Excitation

• This charge separation is known as a membrane • In general each muscle is
potential (abbreviated Vm). served by one nerve – a
bundle of axons carrying
• The value for Vm in inactive muscle cells is signals from the spinal cord
typically btwn –80 and –90 millivolts. to the muscle.

• Cells that exhibit a Vm are said to be polarized. • W/i the muscle, each axon
will go its own way and
– Why do you suppose that is? eventually branch into
multiple small extensions
• Vm can be changed by influx or efflux of called telodendria. Each
charge. 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.

Excitation Excitation

• The PM has integral proteins that act as gated ion channels. These The minute space between the synaptic end bulb and
are channels that are normally closed, but in response to a certain the sarcolemma is known as the synaptic cleft.
signal, they will open and allow specific ions to pass through them.
There is a depression in the sarcolemma at the
• Ion channels may be: synaptic cleft known as the motor end plate.
– Ligand-gated Æ the binding of an extracellular molecule (e.g.,
hormone, neurotransmitter) causes these channels to open. The synaptic end
– Voltage-gated Æ ΔVm causes these channels to open. bulb is filled w/
– Mechanically-gated Æ stretch or mechanical pressure opens vesicles that
these channels. contain the
neurotransmitter,
• When a channel is open, its specific ion(s) will enter or exit acetylcholine.
depending on their electrochemical gradient.
The motor end
plate is chock full
of acetylcholine
receptors.

41

Excitation Excitation

1. A nerve signal will arrive at the synaptic end bulb and this • If the Vm fails to depolarize to threshold,
will cause the ACh-containing vesicles to undergo nothing will happen. The Vm will soon
exocytosis. return to normal and no muscle
contraction will occur.
2. ACh will diffuse across the synaptic cleft and bind to the
ACh receptors. These receptors are actually ligand-gated • If the Vm does reach threshold, 2 types of
Na+ channels. The binding of ACh causes them to open. voltage-gated ion channels will open:

3. Na+ will rush – Fast Na+ channels
into the cell, – Slow K+ channels
making the
local cell
interior more
positive. This
is known as
depolarization.
It is a local
event!

Excitation • If Vm reaches threshold, fast Na+ channels open and Na+
rushes in causing the Vm to depolarize to +30mV. The
• Adjacent to the motor end plate, the sarcolemma depolarization stops when the Na+ channels become
contains voltage-gated ion channels. In order inactivated.
for these channels to open, the Vm must
depolarize from its resting value of –90mV to • At this point, slow K+ channels have opened & K+ efflux
approximately –50mV. This is the threshold. Vm occurs. This returns Vm back to its resting level. This is
must become this positive for the voltage-gated repolarization.
channels to open.
• If we were to graph this change in Vm over time, it would
• The degree of depolarization depends on how look somewhat like the animation below.
much Na+ influx occurred which in turn depends
on how many Na+ channels were opened by • This is known as an action potential.
binding ACh.

42

• An AP can propagate Excitation-Contraction
itself across the surface Coupling
of the PM.
• The T-tubular sarcolemma contains voltage sensitive
• The depolarization proteins (red arrow in the picture below) that change their
caused by the Na+ influx conformation in response to a significant ΔVm.
in one particular area of
the sarcolemma causes – These are physically linked to calcium channels in the SR membrane
voltage-gated channels – Upon ΔVm, the voltage sensors change their conformation. This
in the adjacent
membrane to open. The mechanically opens the Ca2+ channels in the SR membrane.
resulting ionic influx then
causes voltage-gated
channels to open in the
next patch of membrane
and so on and so on.
Thus the AP propagates
itself.

Excitation-Contraction Coupling Excitation-Contraction
Coupling
The AP travels along the sarcolemma going in both directions
away from the motor end plate. The SR Ca2+ channels are only open briefly, but a large
Since T-tubules are simply invaginations of the sarcolemma, Ca2+ gradient exists so a large amount of calcium enters the
the AP will spread down and through them as well. This is sarcoplasm.
really important!
The Ca2+
interacts w/ the 2
regulatory
proteins of the
sarcomere so that
the 2 contractile
proteins can slide
& the sarcomere
can shorten.

43

Let’s backtrack for just a moment… Contractio
n
• Now that we know what an action potential
is, it should be noted that the exocytosis of • Once actin’s myosin binding site is exposed, myosin will
the ACh vesicles is caused by the arrival attach to it.
of an AP at the synaptic end bulb.
– At this point myosin has just hydrolyzed ATP into ADP and Pi –
• The AP causes the opening of voltage- however both molecules are still bound to the myosin.
gated Ca2+ channels in the synaptic end
bulb plasma membrane. The resulting – The ATP hydrolysis provides the energy for the “cocking” of the
calcium influx causes the exocytosis of the myosin head
vesicles.
• 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.

• Normally, Contraction
tropomyosin
obstructs the
myosin binding
site on the G-actin
subunits.

• 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.

44

• The cycle of attachment, power stroke, and release Contraction Strength
continues as long as calcium and ATP remain available.
• Is a function of:
• Typically half the myosin molecules at any time are bound
to the actin while the other half are preparing to bind 1. The number of crossbridges that can be
again. made per myofibril

• A common analogy is climbing a rope hand over hand. 2. The number of myofibrils per muscle fiber
3. The number of contracting muscle fibers

Relaxation

• Calcium pumps in the SR membrane work
constantly to get the calcium out of the
sarcoplasm and back into the SR.

• 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 sarcolemma and free w/i the synaptic
cleft

45

Relaxation Rigor Mortis

• When the muscle ceases being • Upon death, muscle cells are unable to
stimulated, the calcium pumps prevent calcium entry. This allows myosin to
“win” and sarcoplasmic [Ca2+] bind to actin. Since there is no ATP made
drops. postmortem, the myosin cannot unbind and
the body remains in a state of muscular rigidity
– Calcium stops being for almost the next couple days.
available for troponin and
tropomyosin shifts back into This animation shows another way to
its inhibitory position. induce muscle relaxation. Does it
make sense?
• The muscle then returns back to
its original length via the
elasticity of the connective tissue
elements, plus the contraction of
antagonistic muscles, and
gravity.

QUICK THOUGHT QUESTION: In this sculpture, why are Muscle Metabolism
the lion’s back legs paralyzed even though they were not
injured? • 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.

46

Resting Muscle Krebs Cycle Products

and the Krebs • CO2 will diffuse out of the mitochondria,
out of the muscle fiber, and into to the
Cycle blood stream which will take it to the lungs.

• Resting muscle fibers typically • The ATP made in the Krebs cycle plus the
takes up fatty acids from the blood ATP made during the ETC will be used in
stream. many ways.

– How might they enter the cell? – See if you can list at least 5!

– 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 rxns. The end
product of these rxns is CO2, ATP,
NADH, FADH2, and oxaloacetate (thus
we call it a cycle)

Krebs Cycle ATP Use in the Resting Muscle
Products
Cell
Oxaloacetate will simply
combine with another • ATP is necessary for cellular housekeeping
molecule of acetyl-CoA and duties.
reenter the cycle.
• ATP powers the combination of glucose
NADH and FADH will enter another series of rxns known as monomers (which have been taken up from the
the Electron Transport Chain. These rxns occur along the inner blood stream) into the storage polymer
membrane of the mitochondrion and they basically consist of glycogen.
the passing of electrons from compound to compound with
energy being released each time and used to drive the synthesis • ATP is used to create another energy storage
of ATP. The final electron acceptor is oxygen when it combines compound called creatine phosphate or
with 2 hydrogen atoms to yield water. phosphocreatine:

ATP + Creatine Î ADP + Creatine-Phosphate

this rxn is catalyzed by the enzyme creatine
kinase

47

Working Muscle Working Muscle

• As we begin to exercise, we almost immediately • After the phosphagen system is depleted, the
use our stored ATP. muscles must find another ATP source.

• For the next 15 seconds or so, we turn to the • The process of anaerobic metabolism can
phosphagen system, a.k.a., the energy stored in maintain ATP supply for about 45-60s.
creatine-phosphate.
• Anaerobic means “without air,” and it is the
Creatine-P + ADP Creatine Kinase Creatine + ATP breakdown of glucose without the presence of
– The ATP is then available to power contraction and oxygen.

relaxation: myosin ATPase, Ca2+ ATPase in the SR – It usually takes a little time for the respiratory and
membrane, and Na+/K+ ATPase in the sarcolemma. cardiovascular systems to catch up with the muscles
– The phosphagen system dominates in events such as and supply O2 for aerobic metabolism.
the 100m dash or lifting weights.

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
and the conversion of 2 molecules of NAD+
into NADH. This process is known as
glycolysis and it occurs in the sarcoplasm.

– Unfortunately, w/o 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+

48

Anaerobic Aerobic

Metabolism Metabolism

• Lactic acid typically diffuses out • It occurs in the
of muscles into the blood mitochondria.
stream and is taken to the liver,
kidneys, or heart which can use • Pyruvic acid from
it as an energy source. glycolysis is the primary
substrate. The cell also
• Anaerobic metabolism is utilizes fatty acids and
inefficient. Large amounts of amino acids.
glucose are used for very small
ATP returns. Plus, lactic acid • Aerobic respiration
is a toxic end product whose typically yields 36 ATP
presence contributes to muscle per molecule of glucose.
fatigue. Compare this to
anaerobic metabolism.
• Anaerobic metabolism
dominates in sports that
requires bursts of speed and
activity, e.g., basketball.

Aerobic Metabolism Muscle Fatigue

• Occurs when the respiratory and • Physiological inability to contract
cardiovascular systems have “caught up with” • Results primarily from a relative deficit
the working muscles.
of ATP.
– Prior to this, some aerobic respiration will occur • Other contributing factors include the
thanks to the muscle protein, myoglobin, which
binds and stores oxygen. decrease in sarcoplasmic pH (what
causes this?), increased sarcoplasmic
• During rest and light to moderate exercise, [ADP], and ionic imbalances.
aerobic metabolism contributes 95% of the
necessary ATP.

• Compounds which can be aerobically
metabolized include:

– Pyruvic acid (made via glycolysis), fatty acids, and
amino acids.

49

Oxygen Debt

• Refers to the fact that post-exercise breathing
rate >>> 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 restore resting ionic

conditions within the cell.

Whole Muscle Contraction Phases of the Muscle Twitch

• Why can you electrically stimulate a muscle 1. Latent Period
to contract? (HINT: what kind of channels
could an electric current open?) – Time btwn stimulus and generation of
tension
• A sub-threshold stimulus would not cause
contraction because no AP would be – Includes all time required for excitation,
produced! excitation-contraction coupling, and
stretching of the series elastic
• The response of a muscle to a single supra- components.
threshold stimulus would be a twitch – the
muscle quickly contracts and then relaxes. 2. Contraction
3. Relaxation
• Let’s take a look at a measurement of a
neuron’s AP, a muscle fiber’s AP, and the Now, let’s look at various types of muscle twitches
tension developed by that muscle fiber.

50