Excitation-Contraction Coupling:
At the heart of muscle function
HOOK
• Muscle is only biological cell/tissue that
can cause rapid, large-scale movement—
THE evolutionary innovation that defines
animals….and ourselves.
• Role of excitable membrane and
filamentous muscle proteins understood
as great and early breakthrough in
cell/molecular biology and biochemistry
Larry M. Frolich, Ph.D.
March 17,2011
How does muscle work—outline
• Motor Unit—motor neuron plus skeletal muscle
cells (review)
• Action potential in neurons (reminder)
• Muscle cell architecture
• From arrival of an action potential to the
contraction of the muscle (excitation-contraction
coupling)
• Molecular basis of muscle movement—sliding
filament model
• Whole muscles and their physiology as
explained by the molecular/cellular basis of
muscle function (lab activities)
The Motor Unit (review)
• Neurons and Muscle Cells
are unique to animals
• They have “excitable”
membranes that transmit
action potentials
• They allow for rapid
large-scale movements
• Motor Unit is one motor
neuron plus the muscle
cells that it stimulates (or
synapses with)--the
minimal construct that
allows for movement in
our body
REMINDER SLIDE
How do neurons carry a message—
action potentials
Muscle cell architecture
Single muscle cell or muscle “fiber” is composed of myofibrils
which contain sarcomeres or contractile “units”
Myo (Latin for
muscle)
Sarco (Greek
for flesh)
Muscle cells
• Skeletal muscle fibers are BIG cells—visible to naked eye
as fibers in meat, chicken, fish
• Sarcolemma is muscle cell membrane—”excitable” so has
action potentials just like neurons
• Because cell is large, T-tubules carry action potential—
ionic depolarization—into internal parts of cell
• Ionic depolarization in T-tubules causes sarcoplasmic
reticulum to releases calcium
• Calcium triggers actin-myosin protein filaments to “slide”
against each other.
From action
potential to
movement of
muscle cell
The Brain From Top to Bottom
Molecular Basis of Muscle Contraction
•
Actin-Myosin
“sliding filament”
model
• Actin and myosin
filamentous proteins
are packed parallel
and end-to-end in
sarcomeres
• When muscle cell is
“excited”
(experiences action
potential), Ca is
released causing
sarcomeres to
contract
How does the actin-myosin complex (sarcomere)
shorten and contract the muscle?
•
Actin = thin filament
“lattice-work”
• Myosin = thick filament
“core”
• Ca release triggers the
formation of molecular
cross-bridges from myosin
to actin
• Cross-bridges “row” or
“reach” for more adjacent
binding site on actin.
(would normally draw on board)
Biochemical artwork by David Goodsell –see more here
A
Details, details, details…
• Tropomyosin and troponin
create binding site on actin
filament
• Presence of Ca++ exposes
binding site
• “Cocked” cross-bridge on
myosin (uses ATP) then
attaches to binding site and
pulls or “rows” actin filament
• Cross-bridge linkage is
broken and re-cocks to link
with next binding site
And the result is
muscle movement
Whole muscle
Excitation-Contraction Coupling and
Sliding Filament Model explains:
• Why muscle has peak
force at middle lengths:
(ideal actin-myosin
overlap for cross-bridge
formation)—BUCKET
DEMO
• More muscle cells
active (“excited”) means
more muscle force:
(more cross-bridge
formation)—
• EMG’S
• ISOLATED MUSCLE LAB
Excitation-Contraction Coupling and
Sliding Filament Model also explains:
• Concentric/isometric/eccentri
c contraction: Cross-bridges
continue to form and “reach”
even if opposing force is
greater.
• Striations (background of
slide)—MICROSCOPE SLIDES
• Arm-raising ghost effect after
pushing against doorway—DOAT-HOME DEMO
Want more details
(from 2008 Nature review)
“you'll thank me later” (for
protecting from too much detail)
Evolutionary tinkering
(where did this incredible system come from?:
• Actin is present in
all eukaryotic cell as
part of internal cell
architecture
• Myosin is present
as “motor protein”
that hauls other
structures along the
actin highways
G
So, go get your actin and myosin sliding…
Gracias por su atención.
More info on Frolich website: http://faculty.yc.edu/lfrolich/index.htm
Excitation-Contraction Coupling and
Sliding Filament Model explains:
• Why muscle has peak force at
middle lengths: (ideal actinmyosin overlap for crossbridge formation)—BUCKET
DEMO
• More muscle cells active
(“excited”) means more
muscle force: (more crossbridge formation)—EMG’S,
ISOLATED MUSCLE LAB
• Concentric/isometric/eccentri
c contraction: Cross-bridges
continue to form and “reach”
even if opposing force is
greater.
•
•
Striations (background of slide)—
MICROSCOPE SLIDES
Arm-raising ghost effect after pushing
against doorway—DO-AT-HOME DEMO