PHYSIOLOGY

1. PHYSIOLOGY DEN 1003 ANP 1001 Prepared by: Dr. D. Boyd

2. MUSCULOSKELETAL PHYSIOLOGY • Muscle cells are specialized for contraction • Action potential transmitted along the sarcolemma (muscle cell membrane)  activates contractile mechanism • 3 Types of Muscles: • Skeletal (striated; striped under microscope) • Under voluntary control • Rapid acting

3. MUSCULOSKELETAL PHYSIOLOGY • 3 Types of Muscles: (cont) • Smooth (blood vessel walls & internal organs) • Involuntary (inherent rhythmic contraction) • Slow acting • Cardiac: striated, features of both skeletal, & smooth muscle

4. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • Composed of many parallel muscle fibers (myofibers) • Myofibers: • Run length of muscle • Terminate in tendons that attach fiber to Skeletal system. • Multi-nucleated structure • Surrounded by sarcolemma

5. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • A. Structural Changes During Contraction • 1. Shortening: • Result from increase in extent of thin-thick filament overlap • Thin filament (Actin) slide over  Thick filament (Myosin) center of sarcomere (unit of myofiber) • “sliding filament mechanism” • Sarcomere length decreases • Length of filaments do not change

6. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE Z line Sarcomere A band (dark) Actin Contraction Myosin I band (light) Z line I & H bands shorten H band Relaxed State Contracted State Contraction of Sarcomere

7. MUSCULOSKELETAL PHYSIOLOGY Molecular Aspects of Contraction Pi Actin ADP-Pi ATP Myosin ADP ATP ATP THE CONTRACTILE CYCLE (mechanochemical coupling)

8. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • 2. Molecular Aspects of Contraction • Upon stimulation of myofiber, myosin heads with (ADP + Pi) connect with actin filaments • Actin-myosin complex form (ADP + Pi released) • Actin-myosin bond broken (ATP added) • Cycle repeated • CLINICAL CORRELATION • No ATP, myosin heads can NOT release, leads to stable actin-myosin complex  rigor mortis

9. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • B. Excitation-Contraction Coupling • Action Potential generated by motor neuron initiates mechanical contraction • AP transmitted along muscle membrane, down T tubule to sarcoplasmic reticulum • Cytoplasmic Ca++ released • Ca++ contact myosin & actin filaments • Site on actin expose that binds to myosin • Ca++-ATPase (sarcoplasmic reticulum) depletes Ca • Filaments return to inactivated state

10. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • C. Summary of Contraction Sequence • AP get to end of axon • ACh released at neuromuscular junction • ACh diffuse across gap • Nicotinic ACh receptor at end-plates react with ACh • Muscle cell membrane depolarized • AP travel along muscle cell membrane • T tubule depolarization, travel to sarcoplasmic reticulum  Ca++ release into cytoplasm

11. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • C. Summary of Contraction Sequence (cont) • Ca++ binds to troponin-tropomyosin • Myosin heads bind to actin • Myosin-ATPase activated • Cross-bridges attach & detach • Myosin & actin slide past each other • Sarcoplasmic reticulum pumps Ca++ back into lumen • Ca++ removed from tropin-tropomyosin ` complex & actin-myosin interaction inhihited

12. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • Single Action Potential  muscle twitch, brief contraction followed by relaxation • Twitch starts 2 msec after depolarization of membrane begins, i.e. during re-polarization. Action Potential Peak of Contraction Start of Electrical Response Muscle Twitch Relative Timing of AP & Muscle Contraction Contraction Time

13. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • CLINICAL CORRELATION: • Ca++ re-uptake mechanism of the sarcoplasmic reticulum = Ryanodine Receptor • In some people this receptor is blocked by general anesthetic with succinylcholine. • Ca++ is NOT taken up quickly enough and muscles “overcontract”, generating enormous amounts of heat (malignant hyperthermia), which can be fatal if not treated with dantroline.

14. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • D. Muscle Mechanics • Most physical activity include both isometric & isotonic contractions • 1. Definitions: • Isometric contraction: • Both ends of muscle are fixed • No change in length during contraction • Tension (force) increases • E.g. pushing against a wall

15. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • D. Muscle Mechanics • 1. Definitions: (cont) • Isotonic contraction • Muscle shorten during contraction • Tension (force) remains constant • E.g. lifting weights

16. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • D. Muscle Mechanics • 1. Definitions: (cont) • Dynamic contraction • Muscle length & force change during contraction • Muscle may shorten = concentric contraction • Muscle may be pulled out by load = eccentric contraction

17. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • D. Muscle Mechanics • 2. Length-Tension Relationship • Tension developed in an isometric contraction varies with the initial length of the muscle fiber. • There an optimal length at which a muscle is able to develop maximum tension. Tmax Passive Tension Tension Active Tension Lopt Length of Muscle

18. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • NOTE: • Sarcomeres (in series) of the same myofibril do NOT generate additive force • To generate more force, more fibers must be recruited (in parallel)

19. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • Isotonic Contraction • The velocity at which the muscle contracts varies inversely with the load it lifts. • At 0 load there is rapid but finite velocity of shortening • With increasing load the velocity approaches 0. • At 0 velocity contraction becomes iosometric. • This point = maximum active force of muscle

20. MUSCULOSKELETAL PHYSIOLOGY • SKELETAL MUSCLE • Isotonic Contraction Isometric Contraction Maximum Force Force 0 Initial Velocity of Contraction Force-Velocity Relationship in Skeletal Muscle

21. MUSCULOSKELETAL PHYSIOLOGY • E. Types of Skeletal Muscle Fibers • Property Fast Twitch Slow Twitch • & Type • Color White Red • SR & T tubules Many Few • Myosin ATPase High Low • Mitrochondria Few (short, Many (sustained rapid mov’ts contractions) • SR = sarcoplasmic reticulum

22. MUSCULOSKELETAL PHYSIOLOGY • E. Types of Skeletal Muscle Fibers (cont) • 1. Fast Twitch (Type 11) • White Few fibers per motor unit • Large diameter No myoglobin • Use glycolysis to generate energy, function under anaerobic conditions • Adapted for rapid contraction • Enable fine, careful movements (e.g. contraction of extraocular muscles of Eye, & superior head of Temporalis muscle)

23. MUSCULOSKELETAL PHYSIOLOGY • E. Types of Skeletal Muscle Fibers (cont) • 2. Slow-twitch(Type 1)(muscles of mastication) • Red due presence of myoglobin • Small diameter fibers • Less sarcoplasmic reticulum & Ttubules • Smaller motor end plates • Slow to contract, adapted for long,sustained contraction • Oxidative metabolism used for energy • Large number of mitrochondria & more blood supply

24. MUSCULOSKELETAL PHYSIOLOGY • IN SUMMARY • Fast-twitch (Type 11) vs Slow-twitch (Type 1) • Think of chicken: • White meat (white muscle) (Type 11) found in breast, used for intermittent flapping of wings. • Dark meat (red muscle) (Type 1)found in thighs, used for stained maintenance of posture.

25. MUSCULOSKELETAL PHYSIOLOGY • F. Motor Units • Consists of all the muscles innervated by a single alpha motor nerve axon • Excitation of motor neuron result in contraction of all fibers in the motor unit • Each muscle fibers of a given motor unit is of the same muscle type • If motor nerve is destroyed , all muscle fibers innervate by that neuron atrophy (e.g. spinal injury)

26. MUSCULOSKELETAL PHYSIOLOGY • Twitch & Tetanus • 1. Single Twitch • Elastic elements (tendons, connective tissue) within muscle & between the muscles & its attachments represent “slack” that must be stretched before the active tension generated by the muscle can be exerted. • This time delay for elastic stretch is enough for the active twitch to decline. • Therefore peak tension is never exerted by a single twitch.

27. MUSCULOSKELETAL PHYSIOLOGY Twitch Amplitude & Relative Timing & Amplitude forForce Generated 100 Tetanus Peak Tension (%) 50 Unfused Tetanus (clonus) 25 Response to 2 stimuli Single Twitch Time 0.5 2 1.0 1.5 Tetanus

28. MUSCULOSKELETAL PHYSIOLOGY • Tetanus • Summation (fusion) of Contractions • Result from high frequency neural stimulation over short period of time • Cause partly because elastic elements have been fully stretched from early contractions hence maximum tension develop wit no time for relaxation of fibers • Caused by increased Ca++ availability over repeated contractions

29. MUSCULOSKELETAL PHYSIOLOGY • G. Skeletal MuscleMuscle Receptors: • Two types: • Muscle spindle (embedded within group of fibers) • Golgi Tendon Organs (arranged in tendon in series with myofibers)

30. MUSCULOSKELETAL PHYSIOLOGY • G. SkeletalMuscle Receptors • 1. Muscle Spindle Primary 1a Afferent Gamma Efferent 11 Afferent Nuclear Bag Fiber Poles Nuclear Chain Fiber Intrafusal Fiber & Innervation

31. MUSCULOSKELETAL PHYSIOLOGY • G. Skeletal Muscle Receptors • 1. Muscle Spindle (cont) • Intrafusal fibers = small muscle fibers innervated by small gamma motor neurons • Primary (annulospiral) type 1a Afferent fibers, rapid conducting, innervate center of both the Nuclear Bag & Nuclear Chain • Secondary (flower-spray) type 11 Afferent fibers, slow conducting, innervate Nuclear Chain only

32. MUSCULOSKELETAL PHYSIOLOGY 1. Muscle Spindle (cont) • Motor innervation of Intrafusal fibers = small slow conducting gamma Efferent fibers • Stretching muscle causes stretching & deformation of Muscle Spindle, which result in volley of impulses in Primary Afferent neurons, that synapse directly on alpha motor neurons innervatingextrafusal fibers of the muscle in which the Spindle is embedded. E.g. contraction of the Quadriceps muscle is elicited when the Patella Tendon is tapped leading to the “ knee-jerk reflex”

33. MUSCULOSKELETAL PHYSIOLOGY • Muscle Spindle (cont) Primary Afferent type 1a neurons discharge rapidly during the lengthening of the muscle, therefore respond to length as well a velocity of stretch of the muscle. • Secondary type 11 neurons discharge rapidly during the entire period of stretch of the muscle, therefore respond mainly to length.

34. MUSCULOSKELETAL PHYSIOLOGY • Muscle Spindle (cont) • SUMMARY • Muscle Spindle (intrafusal fibers) contain: • A contractile element innervated by gamma motor neurons • A non-contractile element enveloped by stretch-sensitive afferent neurons • Muscle stretch causes an increase rate of firing from Spindle afferents, resulting in increased firing of alpha motor neurons to cause muscle contraction

35. MUSCULOSKELETAL PHYSIOLOGY • G. Skeletal Muscle Receptors (cont) • 2. Golgi Tendon Organs • Arranged in series with a discrete number of skeletal muscle fibers • When skeletal contracts, the tendon in which the muscle inserts lengthens & stretches the nerve ending of the afferent fibers, causing them to fire.

36. MUSCULOSKELETAL PHYSIOLOGY • G. Skeletal Muscle Receptors (cont) • 2. Golgi Tendon Organs (cont) • Supplied by 1b afferent fibers, which synapse on inhibitory inter-neurons, which synapse with alpha motor neurons, which inhibit contraction which is protective. • SUMMARY • Muscle Spindle sense muscle length • Golgi tendon Organs sense muscle tension

37. MUSCULOSKELETAL PHYSIOLOGY • SMOOTH MUSCLE • Regulate internal environment of the body • Smaller in size & uni-nucleated • Have fewer myofibrils & less organized • Dense bodies on cell membrane & inside cytoplasm act as site of actin filament insertion • Have much less myosin • Have no T tubules & little sarcoplasmic reticulum. • Ca++ enter from extracellular fluid

38. MUSCULOSKELETAL PHYSIOLOGY • SMOOTH MUSCLE • Contraction & Relaxation: • Occur slowly • Involve overlap of actin & myosin • Thin filaments inserted into Dense bodies are pulled closer together by bridging myosin units. • Dense bodies on cell surface are pulled together so that cell is deformed  contraction.