Muscle physiology

muscle molecular physiology

1. Introduction to skeletal muscle Dr AnuPriya J

2. Muscle physiology Muscle , another excitable tissue like the nervous tissue, forms about 50% of the total body weight 40% - skeletal muscle – voluntary & striated 10% - cardiac muscle – involuntary & striated & smooth muscle – involuntary & nonstriated

3. Muscle - Types

4. Skeletal muscle Forms the great mass of somatic musculature Main function is tension development & shortening Under the control of nervous system Coordinated activity of different muscles – provide useful movement & maintainance of posture

5. Skeletal muscle Voluntary & striated Attached to bones at both ends by tendons Fusiform in shape with tapering ends Has a belly & tendons on either side

6. Skeletal muscle Each muscle is enclosed in a connective tissue covering called epimysium which send septa deep into the muscle dividing it into a number of muscle bundles/muscle fascicles. Each muscle bundle is covered by a connective tissue called perimysium which send septa into the muscle bundle Each muscle bundle consists of individual muscle fibers covered by endomysium

7. Structure of skeletal muscle

8. Skeletal muscle is made up of bundles of muscle fibers (muscle cells) . The muscle fibers are arranged longitudinally and parallel to one another Muscle fibers /cells are the building blocks of the muscular system , like the neurons in nervous system. Structure of skeletal muscle

9. Structure of skeletal muscle

10. Structure of skeletal muscle

11. Muscle cell/ muscle fiber is long, cylindrical & multinucleated. The nuclei are peripherally located Diameter varies from 10 to 100 µm Length varies – often extends the entire length of the muscle Structure of skeletal muscle

12. The cell membrane of the muscle fiber /cell is known as sarcolemma Muscle fibers are composed of myofibrils of 1µm diameter, arranged parallel along the long axis of the muscle fiber . They are separated by cytoplasm/ sarcoplasm Smooth ER – Sarcoplasmic reticulum Muscle cell

13. Myofilaments Each myofibril is formed of myofilaments 2 types – thick and thin filaments THICK FILAMENTS – 1500 in number, 1.6µ long, 10-14 nm wide - MYOSIN THIN FILAMENTS – 3000 in number, 1 µ long, 7 nm wide – ACTIN, TROPOMYOSIN & TROPONIN ratio of 7:1:1

14. Myofilaments

15. Myofilaments Each thick filament consists of 500 myosin molecules & each thin filament consists of 300-400 actin , 40-60 tropomyosin , 40-60 troponin molecules ratio 7:1:1

16. Myofilaments The thick and thin filaments practically interdigitate The arrangement of thick and thin filaments in the myofibrils results in the striated appearance of muscle fibers

17. Structure of a myofibril – Electron microscopy

18. Myofibril - myofilaments A cross section of myofibril shows that each thick filament is surrounded by 6 thin filaments & each thin filament is in turn surrounded by 3 thick filaments

19. Transverse / cross section through part of a myofibril

20. Structure of a myofibril – Electron microscopy Electron microscopy shows cross striations & are characteristic of skeletal muscle These cross striations are not visible in unstained preparations & under ordinary microscope The cross striations are of alternate dark and light bands.

21. Sarcomere The portion of the myofibril between two Z lines is known as sarcomere Sarcomere is the structural and functional unit of the myofibril The width of the sarcomere is 2.5 μ . It consists of an A band 1.6 μ & half of I band 0.5 μ on either side (1.6+0.5+0.5 = 2.6 μ )

22. Sarcomere

23. Sarcomere

24. Sarcomere

25. The dark bands are called A band/ Anisotropc band because they are anisotropic to polarised light (i.e., they can rotate the plane of polarised light and are bifringent ) The light bands are called I band/ Isotropic band (they do not rotate the plane of polarised light & hence not bifringent ) Sarcomere

26. A band contains thick filaments & are made up of the protein myosin molecule and are arranged in a parallel fashion. The I bands contain thin filaments made of 3 proteins – actin , tropomyosin and troponin Sarcomere

27. Sarcomere The thick and thin filaments of the myofibrils are arranged in such a way that they ( the A & I bands) coincide with the A & I bands of all myofibrils, thus giving a striated appearance to the skeletal muscle .

28. Sarcomere

29. In the middle of the dark A band, there is a lighter zone(band/area) called as H zone. It is the area where the thin filament do not overlap with the thick filament. In the middle of the H zone, there is a darker line called M line, formed of a protein called myomesin . This binds to fibrils and connects adjacent thick filaments to one another. Sarcomere

30. In the middle of the I band, there is a dark line called the Z line/ Z disk . The thin filaments are attached to the Z line and they extend to either side of the Z line to interdigitate with the thick filament. The Z line passes from myofibril to myofibril, attaching them all the way across the muscle fiber . It is composed of filamentous proteins – α actinin , desmin , vimentin Sarcomere

31. Muscle proteins Myosin & actin are contractile proteins. They are directly involved in tension generation and shortening Troponin and tropomyosin are regulatory proteins. They regulate the actin -myosin interaction. Hence called so.

32. Muscle proteins in Desmin Vimentin

33. Myosin 2 heavy chains, 4 light chains

34. Myosin

35. Myosin The part of the helix projecting out is called the arm The protruding arm and head together called as CROSS BRIDGE

36. Myosin There are 2 hinges; one present between the arm and the body, the other between the head and arm So movements are possible in these places on either directions

37. Myosin Myosin head has Actin binding site Site of ATPase activity – catalytic site that hydrolyses ATP Types of myosin Myosin I – seen in association with cell membrane with one head for myosin end Myosin II – present in skeletal muscle – has 2 heads

38. Myosin Direction of cross bridge opposite in 2 halves of sarcomere – so no cross bridge in centre of sarcomere Tail directed towards center Head away from center Hence no heads but only tails in centre

39. Myosin

40. Actin Double stranded protein Made of F actin which is formed by polymerisation of the globular protein G actin Mol wt 43000 Myosin binding site during muscle contraction

41. Tropomyosin Double stranded protein Mol wt 70000 Long filaments located on the groove between the 2 actin strands Resting state – loosely attached to F actin & physically covers active sites of actin strands So no interaction between actin & myosin in resting state Each tropomyosin covers about 7 active sites on the actin molecule

42. Troponin

43. Thin filament proteins

44. Calcium binds to troponin C – exposure of active sites of actin strands i.e., myosin binding sites

45. Muscle Proteins

46. Structural proteins α Actinin – binds actin to Z line Titin – connects Z line to M line. Provides muscle with its elasticity Nebulin – helps align actin molecules in the actin filament Desmin , Vimentin – associated with Z line Myomesin - M line, formed of a protein called myomesin . This binds to fibrils and connects adjacent thick filaments to one another.

47. Structural proteins Dystrophin glycoprotein complex – structural support and strength to myofibrils, transmits the force generated by the contraction to cytoskeleton Congenital defect – dystrophin gene defect – different muscular dystrophies – largest gene also present in cardiac & smooth muscle & brain

48. Structural proteins

49. Motor point The area on the skin which corresponds to the point of entry of nerve on the muscle. This area, when stimulated, gives the maximum contraction.

50. Motor point In a long nerve, there are several motor points. When the nerve supply to the muscle is intact & when the muscle is stimulated over its motor points, it is the nerve that is stimulated. Clinically, the muscle is stimulated electrically at motor points, to prevent atrophy of the muscle in certain muscular & neurological disorders.

51. Motor unit The motor neuron, its axon & branches, and the muscle fibers supplied by it, constitute a motor unit . The number of muscle fibers supplied by a motor unit varies (the size of the unit varies inversely with the precision of the movement performed by the part)

52. Motor unit In muscles which are concerned with fine, precise, skilled movements, there are only few muscle fibers (3-6) per motor unit ex: muscles of hand, extraocular muscles Whereas, motor units supply 160-200 muscle fibers - back muscles ; 2000 – gastrocnemius muscle One motor unit supplies only one type of muscle fiber . But, in a muscle, there may be more than one motor unit.

53. Motor endplate Site where the axon & muscle fiber meet

54. Classification of skeletal muscle fiber types TYPE I TYPE II A TYPE II B OTHER NAMES Slow oxidative (SO) Fast oxidative glycolytic (FOG) Fast glycolytic (FG) COLOUR Red Red White MYOSIN ATPASE ACTIVITY Slow Fast Fast CALCIUM PUMPING CAPACITY OF SARCOPLASMIC RETICULUM Moderate High High DIAMETER Small Large Large GLYCOLYTIC CAPACITY Moderate High High OXIDATIVE CAPACITY High Moderate Low ASSOCIATED MOTOR UNIT TYPE Slow Fast. Resistant to fatigue (FR) Fast, fatiguable (FF) MEMBRANE POTENTIAL -90 mV -90mV -90mV

55. Classification of skeletal muscle fiber types TYPE I TYPE II A TYPE II B OTHER NAMES Slow oxidative (SO) Fast oxidative glycolytic (FOG) Fast glycolytic (FG) COLOUR Red Red White MYOSIN ATPASE ACTIVITY Slow Fast Fast CALCIUM PUMPING CAPACITY OF SARCOPLASMIC RETICULUM Moderate High High DIAMETER Small Large Large GLYCOLYTIC CAPACITY Moderate High High OXIDATIVE CAPACITY High Moderate Low ASSOCIATED MOTOR UNIT TYPE Slow Fast, Resistant to fatigue (FR) Fast, fatiguable (FF) MEMBRANE POTENTIAL -90 mV -90mV -90mV

56. Types of motor units On the basis of the type of muscle fiber they innervate, and thus on the basis of the duration of their twitch contraction, motor units are divided into: Slow (S) Fast, resistant to fatigue (FR) Fast, fatiguable (FF) motor units

57. Motor units – Size principle The recruitment of motor units during muscle contraction follows a general scheme, the size principle A specific muscle action is developed first by the recruitment of S muscle units that contract relatively slowly to produce controlled contraction. Next , there is recruitment of FR muscle units resulting in a more powerful response over a short period of time. Lastly, FF muscle units recruited for the most demanding tasks. Example : Leg muscle – S for standing foll by FR for walking foll by FS for running

58. Motor units – Size principle The recruitment of motor units during muscle contraction is not random; rather it follows a general scheme, the size principle In general, a specific muscle action is developed first by the recruitment of S muscle units that contract relatively slowly to produce controlled contraction. Next recruitment of FR muscle units resulting in a more powerful response over a short period of time. Lastly, FF muscle units recruited for the most demanding tasks. Example : Leg muscle – S – standing foll by FR-walking foll by FS-running

59. Give reason - Striated appearance of sarcomere on electron microscopy

60. Note : Neuromuscular junction – Axon terminal & a single muscle fiber

61. Sarcotubular system

62. 3 component model of a skeletal muscle Contractile component – thick and thin filaments – myosin,actin Series elastic component – elastic tissue of the muscle that is present in series with the contractile component of the muscle – i.e., the elastic tendon of the muscle Parallel elastic comp – elastic tissue of the muscle that is attached parallel to the contractile component – i.e., the structural elastic tissue of the muscle such as connective tissue sheaths of the muscle, sarcolemma & gap filaments. Presence of this component explains why the muscle regains its original length after it is passively stretched i.e., property of elasticity

63. Thank you

64. Excitation contraction coupling