Muscle Contraction

Muscle Tissue
Muscle is a tissue built of specialized contractile cells, called muscle
cells or muscle fibers or myocytes or myofibers.

There are two main categories of muscle:

1) Striated muscle tissue has alternating light and dark bands (which
come from the organization of the contractile proteins), giving it a
striated appearance. In vertebrates, the striated muscle makes up the
skeletal (most) and cardiac muscle.

2) Smooth muscle tissue also uses contractile proteins, but they are
not organized in the same fashion, so it doesnt have a striated
appearance. In vertebrates, smooth muscle lines the gut, respiratory
tract, blood vessels, etc.
Tissue built to generate contractile force
Neuromuscular Junction
Where neurons and muscles meet
Neuromuscular Junction
Fast chemical transmission at the NMJ
Step-by-step:

1) AP depolarizes terminal

2) Voltage-gated Ca++ channels
open

3) ACh is released into the synapse

4) ACh binds to nictotinic receptors

5) Nicotinic recepors allow Na
+
and
K
+
ion flow, depolarizing the muscle
cell
Neuromuscular Junction
Fast chemical transmission at the NMJ


6) The muscular AP propagates to all
parts of the muscle, perhaps
resulting in contraction

7) Acetylcholinesterase hydrolyzes
ACh into acetate and choline

8) Choline is actively transported
back into the motor neuron terminal.
Neuromuscular Junction
Muscle Contraction
When the current at the muscle is
sufficiently large, the muscle cell
contracts. Exocytosis of each vesicle of
ACh releases a quantum of ACh
(analogous to an EPSP). Approx. 100
quanta are required to initiate an AP in
the muscle. That number can be
released in response to a single AP
reaching the NMJ.
Although each fiber is only innervated by one nerve, there may be
multiple synapses from that nerve, which promotes more synchronous
depolarization of the fiber (which can be 15 cm long in humans).
Skeletal Muscle Organization
Skeletal Muscles are Organized Hierarchically
Skeletal muscle consists of multiple bundles
of muscle fibers

Myofibers are long, multinucleate, cylindrical
cells, organized in parallel

Each myofiber consists of many parallel
myofibril subunits

Each myofibril is composed of repeated
sarcomere subunits

The sarcomere is the fundemental unit of
contraction, which consists of actin and
myosin filaments
Skeletal Muscle Organization
Skeletal Muscles are Organized Hierarchically
Skeletal muscle consists of multiple bundles of muscle fibers
Skeletal Muscle Organization
Skeletal Muscles are Organized Hierarchically
Myofibers are long, multinucleate, cylindrical cells, organized in parallel
Skeletal Muscle Organization
Skeletal Muscles are Organized Hierarchically
Each myofiber consists of many parallel myofibril subunits
Skeletal Muscle Organization
Skeletal Muscles are Organized Hierarchically
Each myofibril is composed of repeated sarcomere subunits
Skeletal Muscle Organization
Skeletal Muscles are Organized Hierarchically
The sarcomere is the fundemental unit of contraction, which consists of
actin and myosin filaments
Sarcomeres
Skeletal muscle fibers are subdivided into repeated 2 m long striated
sarcomeres with a z disk at each end.










Actin (thin) filaments: ~2000 per disk. Attached at their midpoint to z-
disks and project to either side
Myosin (thick) filaments: ~1000 per sarcomere. At the center of each
sarcomere and attach to actin at each end.
Titin filaments: 10% of total muscle mass. Function as elastic bands.
Actin Filaments
The thin filaments
Each actin filament is
composed of:

1) Two twisted, bended
polymer chains of globular
actin molecules
2) Two strands of tropomyosin molecules that lie from end to end in
the grooves formed by the actin chains

3) Troponin molecules attached at intervals to tropomyosin strands

Tropomyosin and troponin act to control whether myosin cross-bridges
can interact with the thin filaments
Myosin Filaments
The thick filaments
Each myosin filament has ~200
myosin heavy chain molecules
arranged in helical pairs.

Each myosin molecule has a
globular head with an actin binding
domain (actin attachment site), a
nucleotide pocket (ATP hydrolysis
site), and a flexible neck with two
light chains of myosin.

The head-neck segment tilts to a
smaller angle when the molecule
interacts with actin.
Muscle Contraction
The Sliding Filament Theory
Muscle Contraction
The Sliding Filament Theory
Muscle Contraction
Molecular interactions of contraction
Muscle Contraction
1) The rigor state
Muscle Contraction
2) ATP binding
Muscle Contraction
3) ATP hydolysis
Muscle Contraction
4) Rebinding to actin
Muscle Contraction
5) Phosphate release and filament sliding
(power stroke)
Muscle Contraction
6) ADP release (back to rigor)
Muscle Contraction
Molecular interactions of contraction
Muscle Contraction
Molecular movement requires ATP and Ca
2+
ions
No Calcium
Calcium ions present
Ca
2+
bound to
troponin
In the absence of Ca
2+
, tropomyosin blocks the myosin binding
sites on the actin filaments
Muscle Contraction
Molecular movement requires ATP and Ca
2+
ions
T-tubules and the SR
Transverse Tubules and the Sarcoplasmic Rectulum membrane systems
The sarcolemma (the myocyte cell
membrane) forms deep transverse
invaginations into the myocyte, called
transverse tubules (or T-tubules).

The T-tubule system is continuous with
the ECF and thus contains extremely
high Ca
2+
concentrations.

The sarcoplasmic recticulum or SR is
a network of longitudinal membrane-
bound tubules contained entirely within
the myocyte between two T-tubules.

Protein receptor channels join the T-
tubules and SR.
T
-
t
u
b
u
l
e

The SR
NMJ
Muscle cell
Axon
terminal
RyR and DHPR Channels
Ryanodine Receptors and Dihydropyridine Receptors
At the T-tubule-SR junction, the SR
contains a Ca
2+
channel/receptor, called
a ryanodine receptor (RyR). The T-
tubule contains another receptor (this
one not a channel) called a
dihydropyridine receptor (DHPR).

In skeletal muscle, RyR and DHPR form
a complex at the T-tubule-SR junction.
DHPR is activated by T-tubule
depolarization, which stimulates RyR to
release Ca
2+
(Ca
2+
efflux from the SR into
the cytoplasm).
T
-
t
u
b
u
l
e

The SR
Muscle cell
DHPR
Receptor
RyR
Channel
Excitation-Contraction Coupling
Sarcolemma Depolarization
1) ACh release at the NMJ
2) Opening of ACh gated ion
channels
3) AP propagates down the T-tubules

O
O
O
Excitation-Contraction Coupling
Ca
2+
efflux from the SR
4) Depolarization reaches the DHPR
receptors, opening the associated
RyR receptors and releasing Ca
2+

from the SR
5) Ca
2+
ions diffuse into the cytosol
and bind to troponin, enabling
filament sliding
6) Cross bridges go through several
cycles of movement while the Ca
2+

is present.
O
O
O
Excitation-Contraction Coupling
AP termination
7) Meanwhile at the NMJ,
acetylcholinesterase (AChE)
hydrolizes ACh to terminate the AP
8) Depolarization ceases at the T-
tubules and RyR channels close
9) Ca
2+
ATPases actively transport
Ca
2+
ions back into the SR
O
O
O
Excitation-Contraction Coupling
Ca
2+
efflux mediates filament sliding
Relaxed Contracted