Excitation-Contraction Coupling: At the heart of muscle function

Larry M. Frolich, Ph.D.March 17,2011

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

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

How do neurons carry a message—action potentials

REMINDER SLIDE

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 cell architecture

• 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.

Muscle cells

The Brain From Top to Bottom

From action potential to movement of muscle cell

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.

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• 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

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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/

eccentric 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

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

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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 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

• Concentric/isometric/eccentric 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