1. PHYSIOLOGY 1 LECTURE 17 SKELETAL MUSCLE FIBER ANATOMY

2. SKELETAL MUSCLE FIBER ANATOMY n OBJECTIVES: The student should; 1. Learn the basics of skeletal muscle anatomy n 2. Learn the relationship of the contractile proteins to each other within the sarcomere n 3. Learn the basic process of skeletal muscle excitation - contraction - coupling n 4. Learn how skeletal muscle terminates contraction.

3. SKELETAL MUSCLE FIBER ANATOMY n The act of skeletal muscle fiber contraction is a complex series of nerve muscle interactions which lead to actin myosin crossbridge cycling and sarcomere shortening thereby shortening the muscle and generating movement.

4. SKELETAL MUSCLE FIBER ANATOMY n A skeletal muscle fiber consists of the tendons at each end of the cell body which is connected to both each other and the cell body by the endomysium layer of connective tissue. n 1. Tendons - Elastic elements similar to rubber bands connect the muscle cell to the bone - Composed of collagen and elastin which merges with the endomysium n 2. Muscle body - The skeletal muscle cell is one of the largest in of the body. These are multinucleated cells and appear banded due to the sarcomere contractile protein structure under a microscope.

5. SKELETAL MUSCLE FIBER ANATOMY

6. n Internal Skeletal Muscle Fiber –1. Myofibril - Series of sarcomeres running the length of the fiber –2. T-tubules –3. Sarcoplasmic reticulum –4. Sarcomere –5. Multinucleated –6. Mitochondria

7. SKELETAL MUSCLE Internal Fiber n Myofibril - n A series of sarcomeres running the length of the skeletal muscle cell.

8. SKELETAL MUSCLE Internal Fiber n T-Tubules - 2 per sarcomere - These are invaginations of the cells outer membrane - they also bring the AP into close approximation to the SR n 3. SR - Ca++ storage

9. SKELETAL MUSCLE Sarcomere Protein Components n The Sarcomere is composed of two units the thick fibers (Myosin) and the thin fibers (Actin-Troponin-Tropomyosin complex)

10. SKELETAL MUSCLE Sarcomere Protein Components n The Thin Fiber - n 1. The thin fiber is composed of a protein monomer forming a polymer of g-Actin subunits. n 2. Tropomyosin a long thin fiber like protein covering 7 actin monomers.

11. SKELETAL MUSCLE Sarcomere Protein Components n Tropin - Composed of three globular proteins n a. Protein I binds to the actin fiber n b. Protein C binds calcium (4) n c. Protein T binds to tropomyosin

12. SKELETAL MUSCLE Sarcomere Protein Components n Action of Tropin - When Ca++ is bound to the C protein the tropin molecule bends inward forcing the tropomyosin to move clear of the myosin head binding sites on actin

13. SKELETAL MUSCLE Sarcomere Protein Components n The Thick Fiber - n The thick fiber is composed of the protein myosin - Myosin is composed of six (6) protein sub units - Two long thin units twisted together with a globular head and four light chain regulatory units. The myosin molecules adhere to one another forming a long fiber with the heads on the outside

14. SKELETAL MUSCLE Sarcomere Structure n Z - Line or Disk - Protein structure which supports the actin fibers n I - Band - Overlaps two sarcomeres the Z disk is center and contains only actin fibers n A - Band - Delineates the Myosin fibers, does not change length during muscle contraction n H - Zone - Contains myosin fibers only centered on M-Line or Disk n M - Line or Disk - The central protein structure of the sarcomere which supports the myosin fibers

15. SKELETAL MUSCLE Sarcomere Structure

16. SKELETAL MUSCLE Propagation of Action Potential n Once an action potential is generated in the skeletal muscle fiber it is propagated over the entire sarcolemma and down the T-tubules (Invaginations of the sarcolemma). The passage of the AP through the T-tubules activates voltage sensitive proteins. These withdraw into the T-tubules opening calcium channels in the sarcoplasmic reticulum causing a major release of calcium ion into the sarcoplasm. Similar to pulling a cork from a bottle.

17. SKELETAL MUSCLE Propagation of Action Potential

19. n The passage of the action potential causes the pillars to withdraw from their plugging position which blocks the sarcoplastic reticulum’s calcium channels. Calcium release is about 1000 fold.

20. SKELETAL MUSCLE Propagation of Action Potential n 3. Calcium release into the sarcoplasm is about 1000 fold or - Ca++ concentration goes from 10 -7 to 10 -4.

21. SKELETAL MUSCLE EXCITATION - CONTRACTION - COUPLING n The molecular process of excitation - contraction - coupling (or crossbridge cycling) is the basis of current thought on how sarcomere contraction occurs.

22. SKELETAL MUSCLE EXCITATION - CONTRACTION - COUPLING n A. Four Ca ++ ions bind to Tropin C n B. Shape change in Tropin moves Tropomyosin away from myosin head binding site on actin n C. Myosin head + ADP - P binds to actin at binding site n D. ADP - P is released from the Myosin head

23. SKELETAL MUSCLE EXCITATION - CONTRACTION - COUPLING

24. n E. The release of ADP and the P group cause a conformational change in myosin resulting in flexure of the myosin head from it’s original 90 o position to an angle of about 45 o moving the actin fiber inward about 10 nm.

25. SKELETAL MUSCLE EXCITATION - CONTRACTION - COUPLING

26. n F. ATP binds to the myosin head causing a conformational change which causes the myosin head to release the actin fiber. n G. The MyosinATPase splits the ATP into ADP - P causing the last conformational change resulting in the return of the myosin head to it’s 90o position ready to repeat the cycle.

27. SKELETAL MUSCLE EXCITATION - CONTRACTION - COUPLING

30. SKELETAL MUSCLE Termination of Contraction n The contraction is terminated when the cytosolic Ca ++ concentration levels fall back to normal 10 -7 molar. This is accomplished by a Sarcoplasmic Reticular Ca ++ ATPase which transports two Ca ++ ions into the SR for every ATP burned.

31. SKELETAL MUSCLE Termination of Contraction

32. SUMMARY n 1. What are the basics of skeletal muscle anatomy? n 2. What is the relationship of the contractile proteins to each other within the sarcomere? n 3. What is the basic process of skeletal muscle excitation - contraction – coupling? n 4. How does skeletal muscle terminate contraction?