1. Muscle physiology

2. homeostasis skeletal muscles contribute to homeostasis by playing a major role in the procurement of food, breathing,heat generation for maintenance of body temperature, and movement away from harm.

3. Introduction Skeletal muscle Cardiac muscle Smooth muscle Striated muscle Unstriated muscle Involuntary muscle voluntary muscle A B A: depending on whether alternating dark and light bands can be seen under LM B: depending on whether they are innervated by the somatic nervous system and are subject to voluntary control

4. The structure of skeletal muscle Skeletal muscle are stimulated to contract via release of Ach at neuromuscular junctions between motor neuron terminals and muscle cells To understand how the muscle Ap initiated by Ach bring about contraction, firstly you must know the structural components of a skeletal muscle fiber

5. The levels of organization in a skeletal muscle can be summarized as follows: The structure of skeletal muscle Whole muscle An organ Muscle fiber A cell myofibril A specialized intracellular structure Thick and thin filaments Cytoskeletal elements Myosin and actin proteins

6. The structure of skeletal muscle Levels of organization in a skeletal muscle Enlargement of a cross section of a whole muscle

7. The structure of skeletal muscle Seen under light microscope Enlargement of a myofibril within a muscle fiber A myofibril displays alternating dark band (the A bands ) and light bands (the I bands) the bands of all the myofibrils lined up parallel to each other lead to the striated appearance

8. The structure of skeletal muscle Cytoskeletal components of a myofibril Alternate stacked sets of thick and thin filaments that slightly overlap each other are responsible for the A and I bands

9. A band : a stacked set of thick filaments along with the portions of the thin filaments that overlap on both ends of the thick filaments H zone : lighter area within the middle of the A band I band : the remaining portion of the thin filaments that do not project into the A band (only thin filaments) Z line : in the middle of each I band, hold the Sarcomere together Sarcomere : the area between two Z lines, the functional unit of skeletal muscle M line : in the middle of each A band, within the center of the H zone

10. The structure of skeletal muscle Protein components of thick and thin filaments

11. Structure of thick filaments Structure of myosin molecules and their organization within a thick filament The head of myosin form cross bridge (actin binding site and a myosin ATPase site—ATP splitting site)

12. Structure of thin filaments Composition of a thin filament Three protein: Actin: binding of actin and myosin molecules at the cross bridges results in energy- consuming contraction of the muscle fiber Tropomyosin: covers the actin sites that bind with the cross bridges Troponin : has three units – one binds to tropomyosin, one binds to actin and one bind with Ca2+

13. Molecular basis of skeletal muscle contraction— sliding-filament mechanism During contraction, cycles of cross-bridge binding and bending pull the thin filaments inward and closer together between the stationary thick filaments, causing shortening of the sarcomere

14. Changes in banding pattern during shortening. there is no thin filament or thick filament shortening

15. Role of Ca 2+ in turning on cross bridges Muscle fiber relaxed: no cross- bridges binding– its binding site on actins is covered by the troponin- tropomyosin complex Muscle fiber excited: released Ca2+ binds with troponin, pulling the complex aside to expose the binding site; cross-bridges binding actins occurs Binding of actin and myosin cross bridge triggers power stroke that pulls thin filament inward during contraction

16. excitation --?-- contraction

17. Calcium is the link between excitation and contraction (excitation-contraction coupling) excitation-contraction coupling refers to the series of events linking muscle excitation (Ap) to muscle contraction (sarcomere shortening)

18. The structure basis of excitation-contraction coupling The T tubules and sarcoplasmic reticulum in relationship to the myofibrils The T tubules dip deep into the muscle fiber at the junctions between the A and I bands of the myofibrils The sarcoplasmic reticulum is a membranous network runs longitudinally and surrounds each myofibril. The ends of each segment are expanded to form lateral sacs (terminal cisternae)— Ca2+ store

19. How is a change in T tubule potential linked with the release of Ca2+ from the lateral sacs?

21. Excitation-contraction coupling Step 1. Ach released from the terminal of motor neuron cross the cleft and bind to receptors/channe ls on motor end plate – end plated potential occurs

22. Excitation-contraction coupling Step 2. Ap generated and propagated across surface membrane and down T tubules Step 3. Ap triggers Ca2+ release from sarcoplasmic reticulum– ca2+ store SR foot protein ( ryanodine receptors )--- dihydropyridine receptros(T tubule votage-gated sensors.)

23. Excitation-contraction coupling Step 5. myosin cross bridges attach to actin and bend – sarcomere shortened, powered by energy provided by ATP actin binding site and an ATPase site.— enzymatic site (split ATP into ADP and Pi)

24. Excitation-contraction coupling---relaxation Step 6. Ca2+ actively taken up by sarcoplasmic reticulum when there is no Ap Ca2+ -ATPase pump

25. Excitation-contraction coupling Step 7. when Ca2+ no longer bind to troponin, tropomyosin slips back to its blocking position over binding sites on actin. (need ATP) Contract ends; actin slides back to original resting position

26. The relationship of an Ap to the resultant muscle contraction The contraction activity far outlasts the electrical activity that initiated it A single Ap in skeletal muscle fiber lasts only 1 to 2 m sec The duration of the contraction is 100 m sec (contraction time 50 m sec and relaxation time 50m sec)

27. The relationship of an Ap to the resultant muscle twitch The duration of the Ap is not draw to scale but is exaggerated

28. Contractions of a whole muscle can be of varying strength Whole muscle tension depends on: The number of muscle fiber contracting The frequency of stimulation The length of the fiber at the onset of contraction the extent of fatigue The thickness of the fiber

29. Single twitch If a muscle fiber is restimulated after it has completely relaxed, the second twitch is the same magnitude as the first twitch (single twitch)

30. Twitch summation If a muscle fiber is restimulated before it has completely relaxed, the second twitch is added on to the first twitch, resulting in summation. (twitch summation)

31. tetanus If a muscle fiber is restimulated so rapidly that it does not have an opportunity to relaxed at all, a maximal sustained contraction known as tetanus take place.(tetanus)

32. The frequency of stimulation can influence the tension developed by each muscle fiber the single twitch is not of maximal strength, and the tetanus cause maximal strength

33. Why the twitch summation is possible and Ap summation is not ?

34. --- For twitch summation: the duration of the twitch (100 msec) is much longer than the duration of Ap (1to2 msec). When the previous twitch is not complete, the muscle can receive another stimulus --- For Ap: once the Ap is initiated, there is a brief refractory period occurs during which another Ap cannot be initiated

35. What is the mechanism of twitch summation and tetanus at the cellular level? Why the single twitch is not of maximal strength? During the single twitch not all of the cross bridges find a binding sites. (pulling the thin filament to the thick filament). All the released Ca2+ from the first contractile response to be pumped back an identical twitch response will occur The mechanism of twitch summation The first contractile activity is still present when the second Ap takes place. There is another spurt of Ca2+ release,the magnitude of cross-bridge cycling and tension increase The mechanism of tetanus As the frequency of Ap increases, the duration of elevated cytosolic Ca2+ concentration increases, an contractile activity likewise increases until a maximum tetanic contraction is reached. With tetanus, the maximum number of cross-bridge cycling, and tension are at their peak

36. The length of the fiber at the onset of contraction influence the muscle tension There is an optimal muscle length at which maximal tension can be developed upon a subsequent contraction—optimal length(l o )

37. Length-tension relation Maximal tetanic contraction can be achieved when a muscle fiber is at its optimal length (A) The percentage of maximal tetanic contraction will be decrease when the muscle fiber is longer or shorter than (B,C,D) In the body, the resting muscle length is at optimal length. Muscles cannot vary beyond 30% of the optimal length

38. The two primary types of contraction are isotonic and isometric Isotonic contraction: muscle tension remains constant as the muscle changes length Isometric contraction: tension develops at constant muscle length The category of the two types of contraction depend on the relationship between muscle tension and the load

39. Isotonic contraction (tension is less than the load) e.g. you are going to lift an object: The tension in biceps developing and enough to overcome the weight of an subject, then you lift the object and the muscle shortening. The weight of the object does not changes so the tension remains constant during the muscle shortening Significance : body movement and moving an external object

40. e.g. an object is too heavy for you. the tension develop in your muscle is less than that required to lift the load, the muscle cannot shorten and lift the object, the muscle remains at constant length and tension develop Significance : maintaining posture and supporting objects in a fixed position Isometric contraction (the tension exceeds the load) During a given movement, a muscle may shift between the two type. e.g. pick up a book to read (isotonic), as you stop to hold the book in front of you (isometric)

41. Load- velocity relationship The velocity of shortening decreases as the load increases Isotonic contraction: The greater the load, the lower the velocity of shortening a muscle. When the load is maximum the velocity is zero-- Isometric contraction