3. LEARNING OBJECTIVES
Describe molecular characteristics of contractile filaments
Discuss General mechanism of muscle contraction
Discuss the sliding-filament mechanism of sarcomere contraction and explain
how it accounts for tension generation.
Discuss role of ATP as source of energy for contraction
Determine effect of amount of actin and myosin filament overlap on muscle
length, tension and force
4. Guyton and Hall, Textbook of Medical Physiology; 13th Edition, Chapter
6.
Linda Costanzo, Physiology, 6th Edition; Chapter 1.
Vander’s Human Physiology, 14th Edition; Chapter 9.
READING MATERIAL
5. Whole muscle
Bundles or fascicles
of muscle fibres
Muscle fibre
Myofibrils
Sarcomere
Thick
and thin filaments
Myosin and actin
(+ troponin and tropomyosin)
SKELETAL MUSCLE ORGANIZATION
6. THE SARCOMERE
A sarcomere runs from one Z-
line/disc to the next.
It is made up of thick and thin
filaments which overlap.
Z disk is a filamentous network of
protein forming a disk like structure
for attachment of actin myofilament.
7. Each myosin molecule has a flexible cross-bridge that binds
ATP and actin.
THICK FILAMENTS
8. In the relaxed state, myosin binding
sites on actin molecules are covered by
tropomyosin.
Excitation rises calcium level.
Ca2+ binds to troponin C.
Ca2+-troponin C complex interacts
with tropomyosin → uncovering the
myosin binding sites on actin molecules.
Myosin head binds to actin.
THIN FILAMENTS
9. Skeletal Muscle – Overview Of Skeletal Muscle
Contraction
[EXCITATION]
surface membrane depolarization
depolarization of T tubules
[EXCITATION-CONTRACTION COUPLING]
transmission of signal to sarcoplasmic reticulum
release of Ca2+ into myofibrillar space through calcium release channels
[CONTRACTION]
short-range diffusion of calcium to activate sites on thick and thin filaments
resulting in the formation of cross-bridges
[RELAXATION]
re-collection of calcium by active transport (Ca2+ pumps) into
sarcoplasmic reticulum until [Ca2+] in sarcoplasm is below threshold
10. Myosin filaments bind to and move actin filaments → shortening
of stimulated skeletal, smooth, and cardiac muscles.
In all three types of muscle, myosin and actin interactions are
regulated by the availability of calcium ions.
Changes in the membrane potential of muscles are linked to internal
changes in calcium release (and contraction).
SLIDING FILAMENT MECHANISM
11. Muscle contraction is initiated by an increase in intracellular Ca in
skeletal muscle cells.
Under these conditions, Ca2+ binds to troponin C and results in a
conformational change of troponin.
The conformational change of troponin caused by Ca2+ binding results
in tropomyosin being pulled away from myosin binding sites on actin.
This allows myosin head groups to bind to actin binding sites, forming a
cross-bridge and leads to the generation of tension during the muscle
contraction.
SKELETAL MUSCLE – CROSS-BRIDGE
FORMATION
12. In the resting state,
low intracellular Ca,
Actin binding sites are blocked by tropomyosin
Myosin head groups are cocked and have ADP and Pi bound.
In this state, myosin head groups have a high affinity for binding to actin
It cannot bind because of a block by tropomyosin.
When intracellular Ca is elevated,
Troponin C binds Calcium
Tropomyosin is moved away from the binding site,
Actin and myosin bind, forming cross-bridges.
The attached myosin head groups move towards the middle of the thick filament, dragging
the thin filaments over them and shortening the muscle.
During this movement, the head groups release ADP and Pi.
SKELETAL MUSCLE – CROSS-BRIDGE FORMATION
13. When the cross-bridge is formed without ATP or ADP and Pi attached,
Myosin will not de-bind from actin.(because ATP binding reduce the affinity for actin)
Thus, in the absence of cellular ATP, as in dead tissue, cross-bridges remain solidly
attached and the muscle goes into a rigid state called rigor mortis.
If ATP is available,
ATP will bind to the myosin head group, lower its affinity for actin, and cause de-binding.
This is a second effect of ATP in muscle contraction, the plasticizing effect.
When myosin de-binds from actin, it immediately splits ATP into ADP and Pi, raising the
affinity of the head group for actin,
If calcium is still high in the cytoplasm, the myosin head group will bind to another actin
binding site and repeat the cross-bridge cycle until cytoplasmic calcium is once again
brought low.
19. 1
Actin
Cross bridge formation.
Cocking of myosin head. The power (working)
stroke.
Cross bridge
detachment.
Ca2+
Myosin
cross bridge
Thick
filament
Thin filament
ADP
Myosin
Pi
ATP
hydrolysis
ATP
ATP
2
4
3
ADP
Pi
ADP
Pi
20. ATP as the Energy Source for Contraction—Chemical
Events in the Motion of the Myosin Heads.
When a muscle contracts, work is performed and energy is required. Large
amounts of ATP are cleaved to form ADP during the contraction process, and the
greater the amount of work performed by the muscle, the greater the amount of
ATP that is cleaved; this phenomenon is called the Fenn effect.
21. In a normal sarcomere,
The first 0.3 µm is part of an I band, containing only thin filaments.
The next 1.65 µm is the A band, consisting of thick filaments, and on either
end, overlapping thin filaments.
The A band is darker on either end because of the overlap of thick and thin
filaments.
In the center of the A band is a lighter region, the H zone, which consists of
only thick filaments.
In the center of the H zone is a protein line, the M line, that helps to hold the
thick filaments together.
The final 0.3 µm of the sarcomere is part of an I band on the other end of the
sarcomere.
22.
23. During contraction,
The Z lines from either side are pulled towards each other, shortening the sarcomere.
The A band remains at a constant 1.65 µm, but since the overlap of the thick and
thin filaments increases,
the H zone becomes smaller.
The I bands on either side become smaller since the Z lines are being pulled towards
the A bands.
In a muscle, there are hundreds or thousands of sarcomeres in series, and the
shortening of each one contributes to the overall shortening of the muscle.
The force of shortening stretches the tendons on either end of the muscle, generating
the force we recognize as the force of contraction by the muscle.
24. The Sliding Filament Hypothesis
Sarcomere Shortening
Contraction will produce the
following:
A band:
no change in length
I band:
shortens
H zone (band):
shortens
25.
26. Optimal-length sarcomere:
lots of actin-myosin overlap
and plenty of room to slide.
Long sarcomere:
actin and myosin
do not overlap
much, so little
tension can be
developed.
The length-Tension Relationship can be
explained in terms of the sliding-
filament mechanism.
Short sarcomere:
Actin filaments
lack room to slide,
so little tension
can
be developed.
