Skeletal muscle

1. Skeletal muscle Chapter 9 pages 251 - 263

2. 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

3. 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

4. Skeletal muscle fibers • Consist of array of 1 – 2 mm 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

5. Structure of Skeletal Muscle

6. Structure of Skeletal Muscle

7. 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

9. Which of the following molecules are found in sarcomeres? Actin Myosin Tropomyosin Troponin All of the above

10. 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

14. Sarcomere contraction occurs immediately following which step of the cross bridge cycle? Hydrolysis of ATP Binding to actin Release of actin and Pi Binding of another ATP

15. 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

18. 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

19. Which step is required for a presynaptic AP to initiate skeletal muscle fiber contraction? EPSP produced by muscarinic AChRs EPSP produced by nicotinic AChRs IPSP produced by muscarinic AChRs IPSP produced by nicotinic AChRs

20. 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

24. What keeps [Ca2+]i elevated during a 100 ms muscle fiber twitch initiated by a 1 ms AP? Ca2+ ATPases on the cell membrane Ca2+ ATPases on the SR membrane Ca2+-induced Ca2+ release from the SR Voltage-gated Ca2+ channels

25. 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 Sequence of events