2. Organization of the Sarcomere
Proteins of the Myofilament
Organization of Actin Thin Filaments
Organization of Myosin Thick Filaments
The Dystrophin Complex
4. Skeletal muscle
Skeletal Muscles are those which attach to bones and
have the main function of contracting to facilitate
movement of our skeletons.
They are also sometimes known as striated muscles
due to their appearance.
The cause of this 'stripy' appearance is the bands of
Actin and Myosin which form the Sarcomere, found
within the Myofibrils.
5.
6. Smooth muscle
Smooth muscle is also sometimes known as
Involuntary muscle due to our inability to control its
movements, or unstriated as it does not have the
stripy appearance of Skeletal muscle.
Smooth muscle is found in the walls of hollow organs
such as the Stomach, Oesophagus, Bronchi and in
the walls of blood vessels.
7.
8. Cardiac muscle
This type of muscle is found solely in the walls of the
heart.
It has similarities with skeletal muscles in that it is
striated and with smooth muscles in that its
contractions are not under conscious control.
However this type of muscle is highly specialised.
It is under the control of the autonomic nervous
system, however, even without a nervous imput
contractions can occur due to cells called pacemaker
cells
12. Muscle fiber anatomy
Sarcolemma - cell membrane
Surrounds the sarcoplasm (cytoplasm of fiber)
Contains many of the same organelles seen in other cells
An abundance of the oxygen-binding protein myoglobin
Punctuated by openings called the transverse tubules (T-
tubules)
Filled with extracellular fluid
Myofibrils -cylindrical structures within muscle fiber
Are bundles of protein filaments (=myofilaments)
Two types of myofilaments
1. Actin filaments (thin filaments)
2. Myosin filaments (thick filaments)
– When myofibril shortens, muscle shortens (contracts)
13.
14. Organization of sarcomere
A sarcomere is the basic unit of a Muscle.
Muscle cells are composed of tubular Myofibrils.
Myofibrils are composed of repeating sections of
sarcomeres, which appear under the microscope as
dark and light bands.
Sarcomeres are composed of long, fibrous proteins
that slide past each other when the muscles contract
and relax.
15.
16.
17. Myosin forms the thick filament
• Myosin has a long, fibrous tail and a globular head, which
binds to actin.
• The myosin head also binds to ATP, which is the source of
energy for muscle movement.
• Myosin can only bind to actin when the binding sites on actin
are exposed by calcium ions.
Actin forms the thin filament.
• Actin molecules are bound to the Z line, which forms the
borders of the sarcomere.
• Other bands appear when the sarcomere is relaxed.
18.
19. The sarcomeres are what give skeletal
and cardiac muscles their striated appearance
A sarcomere is defined as the segment between two neighboring Z-
lines. In electron micrographs of cross-striated muscle, the Z-
line appears as a series of dark lines.
Surrounding the Z-line is the region of the I-band (for isotropic). I-
band is the zone of thin filaments that is not superimposed by thick
filaments.
Following the I-band is the A-band (for Anisotropic). Named for
their properties under a polarizing microscope. An A-band contains
the entire length of a single thick filament.
Within the A-band is a paler region called the H-zone Named for
their lighter appearance under a polarization microscope.. H-band
is the zone of the thick filaments that is not superimposed by the
thin filaments.
Finally, inside the H-zone is a thin M-line formed of cross-
connecting elements of the cytoskeleton.
22. Organization of Actin Thin Filaments
Thin Filament: composed of 3 major proteins
1. F (fibrous) actin
2. Tropomyosin
3. Troponin
Two strands of fibrous (F) actin form a double helix extending the
length of the myofilament; attached at either end at sarcomere.
Composed of G actin monomers each of which has a myosin-
binding site
Actin site can bind myosin during muscle contraction.
Tropomyosin: an elongated protein winds along the groove of the F
actin double helix.
Troponin is composed of three subunits:
Tn-A : binds to actin
Tn-T :binds to tropomyosin,
Tn-C :binds to calcium ions.
25. Organization of Myosin Thick Filaments
Many elongated myosin molecules shaped like golf clubs.
Single filament contains roughly 300 myosin molecules
Molecule consists of two heavy myosin molecules wound together to form a
rod portion lying parallel to the myosin myofilament and two heads that
extend laterally.
Myosin heads
1. Can bind to active sites on the actin molecules to form cross-bridges.
(Actin binding site)
2. Attached to the rod portion by a hinge region that can bend and
straighten during contraction.
3. Have ATPase activity: activity that breaks down adenosine triphosphate
(ATP), releasing energy. Part of the energy is used to bend the hinge
region of the myosin molecule during contraction
28. Troponin
Troponin is a regulatory protein complex located on the thin filament
of the contractile apparatus and consists of 3 protein subunits:
troponin T, troponin I and troponin C which act to regulate muscle
contraction.
Troponin T (TnT) binds to tropomyosin and anchors the troponin
complex to the tropomyosin of the thin filament.
Troponin I (TnI) inhibits myosin ATPase (inhibits the enzymatic
hydrolysis of adenosine triphosphate that powers muscle
contraction).
Troponin C(TnC) binds to calcium ions.
29. Unlike other cardiac markers that are used to detect
cardiac damage, cTnI and cTnT have different
isoenzymes from those found in skeletal muscle, and
thus they are specific for cardiac injury.
Structure of Troponin Complex
30. Sarcomeric proteins
Titin which is also called connectin, extends from the Z-
line of the sarcomere, where it binds to the thick filament
(myosin)system, to the M-band, where it is thought to
interact with the thick filaments. Titin is the biggest
single highly elasticated protein found in nature.
Myosin binding protein C, also called C protein, which
links the thick filaments,plays a role in sarcomere
formation and contains a number of phosphorylation
sites that regulate contractility.
Myosin binding protein H is present in the purkinje
fibers but not in working cardiac myocytes.
31. M-protein and myomesin contribute to a set of transverse
striations, called M-band, which link the thick filaments
in the center of the A-band. These proteins stabilize
interaction between titin and the thick filaments.
Nebulette is oriented along the axis of the thin filament
and projects from the Z-lines into the I-bands .
Tropomodulin is a capping protein, and is found at the
ends of the of the thin filaments where, by covering the
end of the F-actin polymer, it helps to determine thin
filament length.
α –Actinin and Cap Z (β-actinin) they weave the ends of
thin filaments into the Z-lines at the ends of each
sarcomere.
32. Titin (red) extends from the Z-line to the center of the thick filaments, where it is
linked to myosin by myosin binding protein C (orange). Other proteins that
interact with titin include M-protein, myomesin, obscurin, and ankyrin, which are
found in the M-bands that link adjacent thick filaments in the center of the A-band.
Regions of the titin molecule within the A-band are quite rigid, whereas those in
the I-band are more elastic.
33. Sarcoplasmic Reticulum (SR)
SR is an elaborate, smooth endoplasmic reticulum
runs longitudinally and surrounds each myofibril
Form chambers called terminal cisternae on either side
of the T-tubules
A single T-tubule and the 2 terminal cisternae
form a triad
SR stores Ca2+ when muscle not contracting
When stimulated, calcium released into sarcoplasm
SR membrane has Ca2+ pumps (ATPase) that function to
pump Ca2+ out of the sarcoplasm back into the SR after
contraction
34. The SR is a branched organelle that surrounds the
myofibrils like a net stocking inside the muscle fibers
(illustrated at the top using the example of a heart
muscle cell).
The high Ca2+ level in the SR is maintained by
Ca2+- transporting ATPases .
In addition, the SR also contains calsequestrin, a
protein (55 kDa) that is able to bind numerous Ca2+
- ions via acidic amino acid residues.
37. Muscle contraction controlled by:
A. Neuromuscular junction
B. Sarcoplasmic reticulum (SR)
C. Regulation by calcium ions
38. Neuromuscular junction
Muscle contraction is triggered by motor neurons that
release the neurotransmitter acetylcholine. The
transmitter diffuses through the narrow synaptic cleft
and binds to nicotinic acetylcholine receptors on the
plasma membrane of the muscle cell (the sarcolemma),
thereby opening the ion channels integrated into the
receptors .
This leads to an inflow of Na+, which triggers an action
potential in the sarcolemma. The action potential
propagates from the end plate in all directions and
constantly stimulates the muscle fiber.
With a delay of a few milliseconds, the contractile
mechanism responds to this by contracting the muscle
fiber.
39.
40. Sarcoplasmic reticulum (SR)
The action potential (A) produced at the neuromuscular
junction is transferred in the muscle cell into a transient
increase in the Ca2+ concentration in the cytoplasm of the
muscle fiber (the sarcoplasm).
In the resting state, the Ca2+ level in the sarcoplasm is very
low (less than 10–7 M). By contrast, the sarcoplasmic
reticulum (SR), which corresponds to the ER, contains
Ca2+ ions at a concentration of about 10-3 M.
41. The transfer of the action potential to the SR is made
possible by transverse tubules (T tubules), which
are open to the extracellular space and establish a
close connection with the SR.
At the point of contact with the SR, the action
potential triggers the opening of the Ca2+ channels
on the surface of the sarcolemma.
Calcium ions then leave the SR and enter the
sarcoplasm, where they lead to a rapid increase in
Ca2+ concentrations. This in turn causes the
myofibrils to contract
42.
43. C. Regulation by calcium ions
The biochemical effects of Ca2+ in the cytoplasm are
mediated by special Ca2+-binding proteins (“calcium
sensors”).
These include the annexins, calmodulin, and troponin C
in muscle.
Calmodulin is a relatively small protein (17 kDa) that
occurs in all animal cells. Binding of four Ca2+ ions (light
blue) converts it into a regulatory element. Via a
dramatic conformational change , Ca2+-calmodulin
enters into interaction with other proteins and modulates
their properties. Using this mechanism, Ca2+ ions
regulate the activity of enzymes, ion pumps, and
components of the cytoskeleton.
44. In relaxed muscle, the complex consisting of troponin and
tropomyosin blocks the access of the myosin heads to actin .
Troponin consists of three different subunits (T, C, and I).
The rapid increase in cytoplasmic Ca2+ concentrations caused
by opening of the calcium channels in the SR leads to binding
of Ca2+ to the C subunit of troponin,which closely resembles
calmodulin
This produces a conformational change in troponin that
causes the whole troponin– tropomyosin complex to slip
slightly and expose a binding site for myosin.
This initiates the contraction cycle. After contraction, the
sarcoplasmic Ca2+ concentration is quickly reduced again by
active transport back into the SR.
