Download 2 Lec 3 Muscle Physiology V10

Chapter 9
Muscle
Physiology
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© Annie Leibovitz/Contact
Press Images
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Table 9.3-1 Comparison of Skeletal, Cardiac, and Smooth Muscle
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Characteristics of Muscle Tissue
• All muscles share four main characteristics:
– Excitability:
– Contractility:
– Extensibility:
– Elasticity:
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Muscle Functions
• Four important functions
1. Produce movement: responsible for all
locomotion and manipulation
• Example: walking, digesting, pumping blood
2. Maintain posture and body position
3. Stabilize joints
4. Generate heat as they contract
• Additional functions
– Protect organs, form valves, control pupil size,
cause “goosebumps”
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Figure 9.1 Connective tissue sheaths of skeletal muscle: epimysium, perimysium, and endomysium.
Bone
Epimysium
Epimysium
Perimysium
Tendon
Endomysium
Muscle fiber
in middle of
a fascicle
Blood vessel
Perimysium wrapping a fascicle
Endomysium
(between individual muscle fibers)
Muscle fiber
Fascicle
Perimysium
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Attachments
• Muscles span joints and attach to bones
• Muscles attach to bone in at least two places
– Insertion: attachment to movable bone
– Origin: attachment to immovable or less
movable bone
• Attachments can be direct or indirect
– Direct (fleshy): epimysium fused to periosteum
of bone or perichondrium of cartilage
– Indirect: connective tissue wrappings extend
beyond muscle as ropelike tendon or sheetlike
aponeurosis
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Table 9.1-1 Structure and Organizational Levels of Skeletal Muscle
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Figure 9.2b Microscopic anatomy of a skeletal
muscle fiber.
Diagram of part of a
muscle fiber showing
the myofibrils. One
myofibril extends from
the cut end of the fiber.
Sarcolemma
Mitochondrion
Myofibril
Dark A band
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Light I band Nucleus
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Myofibrils
• Myofibrils are densely packed, rodlike
elements
– Single muscle fiber can contain 1000s
– Accounts for ~80% of muscle cell volume
• Myofibril features
– Striations
– Sarcomeres
– Myofilaments
– Molecular composition of myofilaments
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Figure 9.2c Microscopic anatomy of a skeletal
muscle fiber.
Thin (actin)
filament
Small part of one
myofibril enlarged to
show the myofilaments
responsible for the
banding pattern. Each
sarcomere extends from
one Z disc to the next.
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Z disc
Thick (myosin) I band
filament
H zone
A band
Sarcomere
Z disc
I band
M line
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Striations
• H zone:
• M line:
• Z disc (line):
• Thick filaments:
• Thin filaments:
• Sarcomere:
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Figure 9.2c Microscopic anatomy of a skeletal
muscle fiber.
Thin (actin)
filament
Small part of one
myofibril enlarged to
show the myofilaments
responsible for the
banding pattern. Each
sarcomere extends from
one Z disc to the next.
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Z disc
Thick (myosin) I band
filament
H zone
A band
Sarcomere
Z disc
I band
M line
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Figure 9.2de Microscopic anatomy of a skeletal
muscle fiber.
Z disc
Z disc
Enlargement of
one sarcomere
(sectioned
lengthwise). Notice
the myosin heads
on the thick
filaments.
Thin (actin)
filament
Elastic (titin)
filaments
Thick
(myosin)
filament
Cross-sectional
view of a
sarcomere cut
through in different
locations.
Myosin
filament
Actin
filament
I band
thin filaments
only
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Sarcomere
M line
H zone
thick
filaments
only
M line
Outer edge
of A band
thick filaments
linked by
thick and thin
accessory filaments overlap
proteins
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Figure 9.3-2 Composition of thick and thin filaments.
Thick filament
Each thick filament consists of many myosin molecules
whose heads protrude at opposite ends of the filament.
Portion of a thick filament
Myosin head
Actin-binding sites
Heads
ATPbinding
site
Tail
Flexible hinge region
Myosin molecule
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Figure 9.3-3 Composition of thick and thin filaments
.
Thin filament
A thin filament consists of two strands of actin subunits
twisted into a helix plus two types of regulatory proteins
(troponin and tropomyosin).
Portion of a thin filament
Tropomyosin
Troponin
Actin
Active sites
for myosin
attachment
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Actin subunits
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Figure 9.5 Relationship of the sarcoplasmic reticulum and T tubules to myofibrils of skeletal muscle.
Part of a skeletal
muscle fiber (cell)
I band
A band
I band
Z disc
H zone
Z disc
M
line
Myofibril
Sarcolemma
Sarcolemma
Triad:
• T tubule
• Terminal
cisterns
of the SR (2)
Tubules of
the SR
Myofibrils
Mitochondria
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Sliding Filament Model of Contraction
• Contraction: the activation of cross bridges to
generate force
• Shortening occurs when tension generated by
cross bridges on thin filaments exceeds forces
opposing shortening
• Contraction ends when cross bridges become
inactive
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Sliding Filament Model of Contraction (cont.)
• In the relaxed state, thin and thick filaments overlap
only slightly at ends of A band
• Sliding filament model of contraction states that
during contraction, thin filaments slide past thick
filaments, causing actin and myosin to overlap
more
– Neither thick nor thin filaments change length, just
overlap more
• When nervous system stimulates muscle fiber,
myosin heads are allowed to bind to actin, forming
cross bridges, which cause sliding (contraction)
process to begin
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Figure 9.6-1 Sliding filament model of contraction.
1 Fully relaxed sarcomere of a muscle fiber
Z
l
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H
A
Z
l
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Sliding Filament Model of Contraction (cont.)
• Cross bridge attachments form and break
several times, each time pulling thin filaments a
little closer toward center of sarcome in a
ratcheting action
– Causes shortening of muscle fiber
•
•
•
•
•
•
Z discs are pulled toward M line
I bands shorten
Z discs become closer
H zones disappear
A bands move closer to each other
Review Sliding Filament Theory on IP
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Figure 9.6-2 Sliding filament model of contraction.
2 Fully contracted sarcomere of a muscle fiber
Z
l
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A
Z
l
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9.4 Muscle Fiber Contraction
• Four steps must occur for skeletal muscle to
contract:
1. Nerve stimulation
2. Action potential, an electrical current, must
be generated in sarcolemma
3. Action potential must be propagated along
sarcolemma
4. Intracellular Ca2+ levels must rise briefly
• Steps 1 and 2 occur at neuromuscular junction
• Steps 3 and 4 link electrical signals to contraction,
so referred to as excitation-contraction coupling
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Slide 6
Focus Figure 9.1 When a nerve impulse reaches a neuromuscular junction, acetylcholine (ACh) is
released.
Myelinated axon
of motor neuron
Axon terminal of
neuromuscular
junction
Action
potential (AP)
Sarcolemma of
the muscle fiber
1 Action potential arrives at
axon terminal of motor neuron.
2 Voltage-gated Ca2+
channels open. Ca2+ enters the
axon terminal, moving down its
electrochemical gradient.
3 Ca2+ entry causes ACh (a
neurotransmitter) to be released
by exocytosis.
Ca2+
Ca2+
Axon terminal
of motor neuron
Fusing synaptic
vesicles
ACh
4 ACh diffuses across the
synaptic cleft and binds to its
receptors on the sarcolemma.
5 ACh binding opens ion channels in
the receptors that allow simultaneous
passage of Na + into the muscle fiber and
K+ out of the muscle fiber. More Na+ ions
enter than K+ ions exit, which produces a
local change in the membrane potential
called the end plate potential.
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Synaptic vesicle
containing ACh
Synaptic
cleft
Junctional
folds of
sarcolemma
Sarcoplasm of
muscle fiber
Na+ K+
Postsynaptic membrane
ion channel opens;
ions pass.
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Figure 9.7 The phases leading to muscle fiber contraction.
Action potential (AP) arrives at axon
terminal at neuromuscular junction
ACh released; binds to receptors
on sarcolemma
Phase 1:
Motor neuron
stimulates muscle
fiber (see Focus
Figure 9.1).
Ion permeability of sarcolemma changes
Local change in membrane voltage
(depolarization) occurs
Local depolarization (end plate
potential) ignites AP in sarcolemma
AP travels across the entire sarcolemma
AP travels along T tubules
Phase 2:
Excitation-contraction
coupling occurs (see
Figure 9.8 and Focus
Figure 9.2).
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SR releases Ca2+; Ca2+ binds to
troponin; myosin-binding sites
(active sites) on actin exposed
Myosin heads bind to actin;
contraction begins
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Figure 9.8 Summary of events in the generation and propagation of an action potential in a skeletal
muscle fiber.
ACh-containing
synaptic vesicle
Ca2+
Synaptic
cleft
Ca2+
Axon terminal of
neuromuscular
junction
Slide 4
Closed K+
channel
Open Na+
channel
Na+
K+
Action potential
Wave of
depolarization
1 An end plate potential is generated at the
neuromuscular junction (see Focus Figure 9.1).
2 Depolarization: Generating and propagating an
action potential.
Closed Na+
channel
Open K+
channel
Na+
K+
3 Repolarization: Restoring the sarcolemma to its
initial polarized state (negative inside, positive
outside).
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Membrane potential (mV)
Figure 9.9 Action potential tracing indicates changes in Na+ and K+ ion channels.
+30
0
Na+ channels
close, K+ channels
open
Depolarization
due to Na+ entry
Repolarization
due to K+ exit
Na+
channels
open
K+ channels
closed
-90
0
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10
Time (ms)
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Excitation-Contraction (E-C) Coupling
• Excitation-contraction (E-C) coupling: events
that transmit AP along sarcolemma (excitation)
are coupled to sliding of myofilaments
(contraction)
• AP is propagated along sarcolemma and down
into T tubules, where voltage-sensitive proteins
in tubules stimulate Ca2+ release from SR
– Ca2+ release leads to contraction
• AP is brief and ends before contraction is seen
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Focus Figure 9.2 Excitation-contraction (E-C) coupling is the sequence of events by which transmission
of an action potential along the sarcolemma leads to the sliding of myofilaments.
Steps in E-C Coupling:
Sarcolemma
Voltage-sensitive
tubule protein
Setting the stage
The events at the neuromuscular junction
(NMJ) set the stage for E-C coupling by
providing excitation. Released acetylcholine
binds to receptor proteins on the
sarcolemma and triggers an action potential
in a muscle fiber.
T tubule
Action potential
is generated
Ca2+
ACh
Actin
Sarcolemma
Troponin
T tubule
Muscle fiber
2 Calcium ions are released.
Transmission of the AP along the
T tubules of the triads causes the
voltage-sensitive tubule proteins to
change shape. This shape change
opens the Ca2+ release channels in the
terminal cisterns of the sarcoplasmic
reticulum (SR), allowing Ca2+ to flow
into the cytosol.
C a 2+
r e l e a
s e
c h a n
Terminal
n e l
cistern
of SR
Axon terminal of
motor neuron at NMJ
Synaptic
cleft
Terminal
cistern
of SR
Ca2+
1 The action potential (AP)
propagates along the sarcolemma
and down the
T tubules.
Tropomyosin
blocking active sites
Myosin
Ca2+
Triad
Active sites exposed and
ready for myosin binding
3 Calcium binds to
troponin and removes
the blocking action of
tropomyosin. When Ca2+
binds, troponin changes
shape, exposing binding
sites for myosin (active
sites) on the thin filaments.
One sarcomere
One myofibril
Myosin
cross
bridge
4 Contraction begins:
Myosin binding to actin
forms cross bridges and
contraction (cross bridge
cycling) begins. At this
point, E-C coupling is over.
The aftermath
When the muscle AP ceases, the voltage-sensitive tubule proteins return to their
original shape, closing the Ca2+ release channels of the SR. Ca2+ levels in the
sarcoplasm fall as Ca2+ is continually pumped back into the SR by active
transport. Without Ca2+, the blocking action of tropomyosin is restored,
myosin-actin interaction is inhibited, and relaxation occurs. Each time an AP
arrives at the neuromuscular junction, the sequence of E-C coupling is repeated.
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Muscle Fiber Contraction: Cross Bridge
Cycling (cont.)
• Four steps of the cross bridge cycle
1. Cross bridge formation: high-energy myosin
head attaches to actin thin filament active site
2. Working (power) stroke: myosin head pivots
and pulls thin filament toward M line
3. Cross bridge detachment: ATP attaches to
myosin head, causing cross bridge to detach
4. Cocking of myosin head: energy from
hydrolysis of ATP “cocks” myosin head into
high-energy state
• This energy will be used for power stroke in next cross
bridge cycle
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Focus Figure 9.3 The cross bridge cycle is the series of events during which myosin heads pull thin filaments towardSlide
the 5
center of the sarcomere.
Thin filament
Ca2+
Actin
Myosin
cross bridge
ADP
Pi
Thick filament
Myosin
1 Cross bridge formation. Energized
myosin head attaches to an actin
myofilament, forming a cross bridge.
ADP
ADP
Pi
Pi
ATP
hydrolysis
4 Cocking of the myosin head. As
ATP is hydrolyzed to ADP and Pi , the
myosin head returns to its prestroke
high-energy, or “cocked,” position.*
2 The power (working) stroke. ADP
and Pi are released and the myosin head
pivots and bends, changing to its bent
low-energy state. As a result it pulls the
actin filament toward the M line.
In the absence
of ATP, myosin
heads will not
detach, causing
rigor mortis.
ATP
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*This cycle will continue as long as ATP is
available and Ca2+ is bound to troponin. If
ATP is not available, the cycle stops between
steps 2 and 3 .
3 Cross bridge detachment. After ATP
attaches to myosin, the link between myosin
and actin weakens, and the myosin head
detaches (the cross bridge “breaks”).
ATP
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Role of Calcium (Ca2+) in Contraction
• At low intracellular Ca2+ concentration?
-
• At high intracellular Ca2+ concentration?
-
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ATP is needed ……
• To re-establish RMP at sarcolemma and
synaptic knob
• For detachment and “re-cocking” of myosin
heads
• For sarcoplasmic reticulum to reabsorb Ca++ (
by ATP dependant calcium pump)
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Review Principles of Muscle Mechanics
• Contraction may/may not shorten muscle
– Isometric contraction: no shortening; muscle
tension increases but does not exceed load
– Isotonic contraction: muscle shortens because
muscle tension exceeds load
• Force and duration of contraction vary in
response to stimuli of different frequencies and
intensities
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What if??????
• Ach were not removed from synaptic cleft.
• Little or no ATP could be produced
• The CNS sends volleys of high frequency
impulses to various muscles
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