• When a muscle cell
contracts, the thin filaments slide past the thick filaments, and the sarcomere
• To explore the
molecular structure and functional features of the thin and thick filaments.
• To understand the
sequence of events in a single cross bridge cycle.
• To examine the
sequence of events in multiple cross bridge cycling.
3. Molecular Participants
The chemical players in muscle contraction are:
The next several pages explain how each of these chemicals participate in the
contraction of a sarcomere.
Myosin is a protein molecule found in the thick filaments.
6. Myosin Molecule with Hinged Head
• Myosin has a tail and
two heads (called cross bridges) which will move back and forth, providing the
power stroke for muscle contraction.
7. Myosin Molecule with Hinged Head
• The tail of myosin has
a hinge which allows vertical movement so that the cross-bridge can bind to
8. Myosin ATP Binding Site
• The cross bridge
(head) of myosin has a binding site for ATP.
• Myosin is in its low
energy conformation when the cross bridge is in this position:
9. Energized Cross Bridge
• ATP is a molecule with
a high chemical energy. ATP binds
to myosin heads when they are tilted back in their low energy position.
When ATP is hydrolyzed into ADP and phosphate, the energy is released and
transferred to the myosin head.
• Note that the ATP is
glowing yellow indicating that it's in a high energy state.
After the ATP has been hydrolyzed to ADP and phosphate, the energy is
transferred to the myosin head. Now
the head is glowing to show that it's high energy.
When the myosin head is pointing up, it is in a high energy state.
As myosin functions within muscle cells, it undergoes the following four steps:
10. Actin Binding Site on Myosin
• There are two binding
sites on each myosin head, one for ATP and one for actin.
11. Thin Filaments of the Sarcomere
• Thin filaments are
made of these three protein molecules:
• The major component of
the thin filament, actin is composed of a double strand of actin subunits each
of which contain myosin binding sites.
• The regulatory
protein, tropomyosin, is also part of the thin filament. Tropomyosin twists around the actin. When the sarcomere is not shortening, the position of the
tropomyosin covers the binding sites on the actin subunits and prevents myosin
cross bridge binding.
• Troponin, which is
found periodically along the tropomyosin strand, functions to move the
tropomyosin aside, exposing the myosin binding sites.
15. Calcium Ions
• Role of Calcium in
Calcium Ions are
Released from the Terminal Cisternae
Calcium Ions then
Bind to Troponin
Away from the Myosin Binding Sites on Actin
16. Review of Molecular
Review of participants in the Cross Bridge Cycle:
Will bind to:
Calcium, Tropomyosin, Actin
17. Overview: Single Cross Bridge
• This animation shows a
single cross bridge cycle.
18. Six Steps of Cross Bridge
Cross bridge cycling is broken down into six steps which will be explained in
detail during the next six pages.
19. Step 1: Exposure of Binding
Sites on Actin
• Detail of steps
required to expose the binding sites on actin:
Presence of an
action potential in the muscle cell membrane.
Release of calcium
ions from the terminal cisternae.
Calcium ions rush
into the cytosol and bind to the troponin.
There is a change
in the conformation of the troponin-tropomyosin complex.
tropomyosin slides over, exposing the binding sites on actin.
20. Step 2: Binding of Myosin to
• The animation shows
the hinge on the tail of the myosin bending and the energized myosin head
binding into the actin.
21. Step 3: Power Stroke of the
• Detail of steps shown
in this animation:
The ADP and Pi are
released from the actin.
The myosin head
(cross bridge) tilts backward.
The power stroke
occurs as the thin filament is pulled inward toward the center of the sarcomere.
• There has been a
transfer of energy from the myosin head to the movement of the thin filament.
22. Step 4: Disconnecting the Cross
• This animation shows
ATP binding to the cross bridge, allowing the cross bridge to disconnect from
23. Step 5: Re-energizing the Cross
• In this animation, ATP
is hydrolyzed into ADP and phosphate. The
energy (yellow glow) is transferred from the ATP to the myosin cross bridge,
which points upward.
24. Step 6 Removal of Calcium Ions
• Detail of steps in
Calcium ions fall
off the troponin.
Calcium is taken
back up into the sarcoplasmic reticulum.
the binding sites on actin.
25. Calcium Pumps
• This animation shows
how calcium ions are pumped back into the sarcoplasmic reticulum.
Two calcium ions enter the pump (transport protein embedded in the
membrane of the SR). ATP binds to
the pump and is hydrolyzed into ADP and Pi.
The energy released from ATP hydrolysis is used to change the
conformation of the pump, allowing the calcium ions to move into the lumen of
the SR. ADP and Pi fall off the
pump, allowing it to return to it's original conformation.
• In a relaxed muscle
cell, the concentration of calcium ions about 10,000 lower in the cytosol than
in the SR. During a muscle
contraction, the concentration of calcium in the cytosol increases, but it is
still higher inside the SR. To move
the calcium against the gradient, from the lower concentration in the cytosol to
the higher concentration inside the SR, Active transport is needed.
26. Review: Single Cross Bridge
This animation reviews the entire process of a cross bridge cycle.
• Try to pick out these
27. Multiple Cross Bridge Cycles
During the contraction of a sarcomere about half of the cross bridges are
attached to actin and about half are bound at any given time.
If all the cross bridges detached at the same time, then the thin
filament would slide back on the thick filament.
• Many power strokes
occur to bring the Z lines of the sarcomere closer together during the
contraction of a muscle cell. During
relaxation, the myosin heads detach from the actin and the thin filaments slide
back to their resting position.
• The width of the H
zone decreases during a contraction and increases during relaxation.
• The length of the
sarcomere shortens during a contraction, but the thin and thick filaments do not
shorten, they just slide by each other.
29. Review of the Role of ATP
• Summary of the role
that ATP plays in the contraction of muscle:
1. ATP transfers
its energy to the myosin cross bridge, which in turn energizes the power stroke.
2. ATP disconnects
the myosin cross bridge from the binding site on actin.
3. ATP fuels the
pump that actively transports calcium ions back into the sarcoplasmic reticulum.
• The sequence of events
in a single cross bride cycle includes:
1. In influx of
calcium, triggering the exposure of binding sites on actin.
2. The binding of
myosin to actin.
3. The power stroke
of the cross bridge that causes the sliding of the thin filaments.
4. The binding of
ATP to the cross bridge, which results in the cross bridge disconnecting from
5. The hydrolysis
of ATP, which leads to the re-energizing and repositioning of the cross bridge.
6. The transport of
calcium ions back into the sarcoplasmic reticulum.
• Multiple cross bridge
cycling is coordinated sequentially to prevent all cross bridges from either
being connected or disconnected at the same time.