Skeletal muscle

Chapter 9

pages 251 - 263

Muscle types

Muscles responsible for many mechanical activities of the body

Convert chemical energy (ATP) to mechanical energy (force or motion)

Skeletal – attached to bones to produce motion of joints or attached tissue (skin) Normally under voluntary or conscious control

Smooth muscle – surround various hollow tubes (digestive and urinary tracts, blood vessels, etc) to regulate bulk fluid flow Normally not under voluntary or conscious control

Cardiac – responsible for heartbeat and blood flow Cardiac has many similarities to skeletal muscle Both are known as striated muscle (see below) Also has some similarities with smooth muscle

Skeletal muscle

Individual muscle cells (fibers) form bundles Fibers held together by extracellular connective proteins

(collagen) Muscle fibers overlap to form long bundles that terminate in

connective tissues Tendons – connective tissues that connect muscle to bone Ligaments – connective tissues that connect bone to bone Unlike muscle, tendons and ligaments are not contractile Muscle can only contract, therefore antagonist muscles are

required for opposing movement

Skeletal muscle fibers

Consist of array of 1 – 2 m diameter striated fibers known as myofibrils with interspersed nuclei and mitochondria

Myofibril striation comes from repetitive unit known as sarcomere

Sarcomere consists of interleaved thick and thin filaments

Sarcomere bands observed under light microscope, can’t resolve individual filaments

Structure of Skeletal Muscle

Structure of Skeletal Muscle

Molecular structure of sarcomeres

Thin filaments composed of actin, common structural protein found in all cells

Actin filament is polymer of protein subunits attached via disulfide bridges

Common motif in structural proteins Also wrapped in tropomyosin with interspersed

troponin Discuss their involvement in later slides

Thick filaments composed of myosin, ubiquitous protein involved in all forms of cell motility

Which of the following molecules are found in sarcomeres?

1 2 3 4 5

20% 20% 20%20%20%1. Actin

2. Myosin

3. Tropomyosin

4. Troponin

5. All of the above

Molecular structure of sarcomeres

Myosin molecules terminate in motile heads known as cross bridges that non-covalently attach to actin filaments

Contraction is due to sliding of cross bridges on myosin (thick) filaments along actin (thin) filaments

Contraction produced by interaction of actin, myosin and ATP during cross-bridge cycle Hydrolyzes ATP → ADP Reuse actin and myosin

Sarcomere contraction occurs immediately following which step of the cross bridge cycle?

1 2 3 4

25% 25%25%25%1. Hydrolysis of ATP

2. Binding to actin

3. Release of actin and Pi

4. Binding of another ATP

Regulation of contraction

In presence of ATP, there would be nothing to stop continuous contraction Could control contraction by maintaining low ATP levels until contraction is

desired This would adversely affect other cellular processes

Actin filaments wrapped in tropomyosin with interspersed troponin molecules

Tropomyosin prevents myosin from binding actin Troponin is Ca2+ binding protein that binds tropomyosin to actin When Ca2+ binds to troponin, tropomyosin no longer prevents myosin

from binding actin and contraction proceeds Removal of Ca2+ back to resting levels causes troponin and tropomyosin

to rebind actin and prevent myosin binding ACh release from presynaptic nerve fibers responsible for elevated

intracellular Ca2+ to initiate contraction

Neuromuscular junction

ACh is degraded by acetylcholine esterase Curare (from poisonous S. American tree frog)

antagonist for AChRs Nerve gases inhibit acetylcholine esterase, prevent

removal of Na+ channel inactivation due to prolonged EPSP

Botulinum toxin inhibits ACh release from nerve terminal

Which step is required for a presynaptic AP to initiate skeletal muscle fiber contraction?

1 2 3 4

25% 25%25%25%1. EPSP produced by muscarinic AChRs

2. EPSP produced by nicotinic AChRs

3. IPSP produced by muscarinic AChRs

4. IPSP produced by nicotinic AChRs

Excitation-contraction coupling

Sustained contraction could not be maintained due to brief APs

Intracellular Ca2+ release mechanism results in contraction that lasts up to 100 ms after AP

Sarcoplasmic reticulum (SR) surrounds myofibril A band (actin/myosin overlap) Serves as large intracellular Ca2+ store Muscle fiber version of endoplasmic reticulum (ER)

Interspersed transverse tubules are plasma membrane invaginations that run along I band (actin only) Act as conduit for extracellular fluid

AP initiated at neuromuscular junction propagates along transverse tubule

What keeps [Ca2+]i elevated during a 100 ms muscle fiber twitch initiated by a 1 ms AP?

1 2 3 4

25% 25%25%25%1. Ca2+ ATPases on the cell membrane

2. Ca2+ ATPases on the SR membrane

3. Ca2+-induced Ca2+ release from the SR

4. Voltage-gated Ca2+ channels

Sequence of events

AP propagates to motor neuron axon terminal

Ca2+ enters axon terminal via presynaptic Ca2+ channels

Elevated presynaptic Ca2+ initiates ACh release

ACh binds to postsynaptic AChRs Opening of AChR gated ion channels

produces postsynaptic EPSP EPSP elevates postsynaptic Vm above

AP threshold AP propagates along T tubules Produces conformational change in

postsynaptic Ca2+ channels Conformational change initiates CICR

from Ca2+ store in SR Ca2+ binds to troponin to release

tropomyosin Exposes myosin binding sites on actin

filament

Energized myosin cross bridges bind to actin

1) A + M-ADP-Pi → A-M-ADP-Pi

Cross bridge formation triggers ATP release and produces movement

2) A-M-ADP-Pi → A-M + ADP + Pi + movement

ATP binds to myosin and dissociates cross bridges

3) A-M + ATP → A + M-ATP ATP hydrolysis re-energizes myosin

4) A + M-ATP → A + M-ADP-Pi

Repeat cross bridge cycling as long as Ca2+ is bound to troponin

Cytosolic Ca2+ levels decrease as Ca2+ is pumped back into SR

Removal of Ca2+ from troponin restores tropomyosin block of myosin binding sites on actin filaments

Cross bridge cycle ceases and muscle relaxes