MECHANICS OF SKELETAL MUSCLE

1. MECHANICS OF SKELETAL MUSCLE Dr. AyishaQureshi Assistant Professor MBBS, MPhil

2. A MUSCLE TWITCH

3. The Muscle Twitch A single action potential causes a brief contraction followed by relaxation in the muscle. This is called a single Muscle twitch. • Electrical and mechanical events in a muscle always occur in relation to one another: The electrical event (Action potential) is followed by the mechanical events (contraction). The whole process is called Excitation-contraction coupling. • Twitch starts 2 ms after depolarization of the membrane, before repolarization is complete-----Why the delay?

5. Contractile activity and electrical activity in skeletal muscle: A single action potential in a skeletal muscle fiber lasts only 1 to 2 msec, while a skeletal muscle contraction and relaxation lasts for about 100 msec. The onset of the resulting contractile response lags behind the action potential because the entire excitation–contraction coupling must occur before cross-bridge activity begins. In fact, the action potential is completed before the contraction even begins. Time is take for the following processes: AP to spread down the t-tubule. Release of Ca2+ Ca2+ to attach to Troponin C Power stroke Ca2+ uptake by the ATPase pump in the SR.

6. Length & tension relationship:

7. Length & Tension Relationship • A relationship exists between the length of the muscle before the onset of contraction and the tension (force developed in the muscle) that each contracting fiber can develop at that length. • For every muscle there is an optimal length (lo) at which maximal force can be achieved on a subsequent contraction. • More tension can be achieved when beginning at the optimal muscle length than when the contraction begins with the muscle less than or greater than its optimal length. This length–tension relationship can be explained by the sliding filament mechanism of muscle contraction.

9. Length & Tension relationship Length (L) and Force (F) or tension of a muscle are closely related: • Optimal length (lo): (In the previous slide seen as point A)This is the point where thin filaments optimally overlap the thick filaments. This is also the normal length of the sarcomere. At this point, maximal no. of cross-bridges & actin filaments are accessible to each other for binding & bending. • At lengths greater than Optimal length (lo):(in the previous slide seen as point C) This is when the muscle is passively stretched. The thin filaments are pulled out from between the thick filaments, decreasing the number of actin sites available for cross-bridge binding. So some of the cross-bridge and actin sites “do not match up” and go “unused”. So, NO actin –myosin overlap, tension developed by the muscle is zero. • At lengths less than Optimal length (lo): (in the previous slide seen as point D) If a muscle is shorter less tension is developed for the following reasons: - The thin filaments from the opposite sides become overlapped. - The ends of the filament become forced against the z-discs so no further shortening can take place.

10. Length-Tension Relationship Points to Remember: • When the muscle is at its Optimal length, it contracts with the maximum tension. • Force of contraction (tension generated) is maximal at the resting (Optimal) length & decreases if the muscle is longer or shorter.

11. Energetics of muscle contraction:

12. Energy sources The main source of energy for muscle contraction is ATP. ATP is used in 3 different steps in contraction-relaxation process. These steps are: • Splitting of ATP by myosin ATPase provides the energy for the power stroke of the cross bridge. 2. Binding (but not splitting) of a fresh molecule of ATPto myosin lets the bridge detach from the actin filament at the end of a power stroke so that the cycle can be repeated. This ATP is later split to provide energy for the next stroke of the cross bridge. • Active transport of Ca2+back into the sarcoplasmic reticulum during relaxation depends on energy derived from the breakdown of ATPand is used by the ATP- dependant Calcium Pump. The concentration of ATP in a Muscle fiber= 4mmole. It is sufficient to maintain full contraction for only 1 to 2 seconds at most.

13. SOURCES OF ATP There are 3 main sources of ATP: • Creatine Phosphate/ Phosphagen Energy system: - takes place within the muscle -uses the Phosphate bond from Creatine phosphate - First source of ATP when exercise begins; instantaneous energy available. - short bursts of high-intensity exercise. E.g. high jump, sprints… 2. Oxidative phosphorylation:aerobic or endurance type exercise. - takes place in the mitochondria - requires oxygen & uses fatty acids, glucose in blood and glycogen stores - to sustain long duration mild to moderate aerobic exercise. E.g. walks, jogging, swimming, marathon runners…. 3. Glycolysis:anaerobic or high-intensity exercise - when oxygen demands are not met & oxygen NOT available. - uses glycogen stores of the muscle - proceeds very rapidly and leads to formation of lactic acid. - moderate to severe exercise. E.g. 800 meter run. Cannot be sustained for long time.

15. CHARACTERISTICS/ PROPERTIES OF WHOLE MUSCLE CONTRACTION : We have been talking about muscle fibers as a single muscle cell….. Now we will consider Muscle as a whole consisting of several to several hundred muscle fibers….

16. 1. MUSCLE FATIGUE Definition: Fatigue occurs when prolonged & strong stimulation of an exercising muscle reaches a stage when the muscle is no longer able to respond to the stimulation with the same degree of contractile activity. • Is of 2 main types: • Muscle fatigue: occurs in the muscle & is a defense mechanism that protects the muscle by preventing it from reaching a point where no ATP will be available. • Central fatigue: more psychological. Occurs when CNS no longer activates the motor neurons supplying the muscles. Person stops exercising even though the muscles can still perform.

17. 1. MUSCLE FATIGUE CAUSES: • Depletion of Glycogen energy stores. • Accumulation of Hydrogen ions from lactic acid- interfere with cross- bridge functions. • Intracellular acidosis from lactic acid inhibits glycolysis enzymes & slows ATP production. • NT depletion at the NMJ. • Central fatigue- lack of will & sleep. • Accumulation of extracellular K+

18. 2. OXYGEN DEBT • The body normally contains about 2 liters of oxygen:

19. 2. OXYGEN DEBT • During muscular exercise, a lot more Oxygen is supplied to the muscle than is present. • ↑ O2 consumption = ↑ energy expended • All stored O2 is used within a minute or so • After exercise is over: • 2 liters of normally present blood must be replenished • 9 liters extra must be provided for: • Resynthesis of the Creatine Phosphate. • Conversion of lactate into pyruvate. • Form fresh supplies of ATP through oxidative phosphorylation.

20. 2. OXYGEN DEBT • All this extra Oxygen that must be “repaid” (11.5liters) to the body is called the Oxygen Debt. SO, A person must breathe rapidly even after the exercise is over!

21. 3. MUSCLE TONE Even when muscles are at rest, a certain amount of tautness usually remains—This is called Muscle Tone. Cause: Low rate of nerve impulses coming from the spinal cord which are controlled by the: • Signals from the brain to the spinal cord- anterior motor neurons • Signals that originate in the muscle spindles located in the muscle itself-Intrafusal fibers

22. 4. MOTOR UNIT Definition: All the muscle fibers innervated by a single nerve fiber are called a MOTOR UNIT. OR Each single motor neuron plus all the muscle fibers it innervates is called a MOTOR UNIT. • One motor neuron innervates a number of muscle fibers, but each muscle fiber is supplied by only one motor neuron. When this neuron is stimulated, all the muscle fibers supplied by it contract together. • Each muscle consists of a number of mixed motor units. • For a weak contraction of the whole muscle, only one or a few of its motor units are activated. • The number of muscle fibers per motor unit and the number of motor units per muscle vary widely, depending on the specific function of the muscle. E.g. the kind of work that the muscle performs…..

25. 4. MOTOR UNIT • Number of muscle fibers in a motor unit vary in different muscles from 2 or 3 to more than 1000. • Average: 80-100 muscle fibers to a motor unit. • Muscles which have to perform fine grade, intricate movements have motor units with as few as 3-5 muscle fibers to a unit .e.g. hand, eye • Muscles with relatively crude movements, number of muscle fibers is quite large. E.g. muscles of lower limbs • In one whole muscle, different motor units overlap

26. 5. ALL OR NONE LAW In a single muscle fiber exactly the same as in the single nerve fiber. • A sub-threshold stimulus does not produce a response while a threshold or supra-threshold stimulus produces a maximal response. In whole muscle the response is different. • A gradual ↑ in stimulus strength causes a gradual ↑ in muscle contraction till a maximum is obtained. This is because with each ↑ in stimulus strength more & more motor units are stimulated. • When all motor units are activated---all muscle fibers are contracted , then a further ↑ in the strength of the stimulus is without any additional contractile effect.

27. 6. Force of Contraction Summation: Summation: is the process of adding together of individual twitch contractions to increase the intensity of whole muscle contraction. There are 2 types of summation: • Multiple Fiber Summation (No. of motor units stimulated) • Frequency Summation

28. 6. a: Multiple Fiber Summation Definition: It is the summation of individual muscle fiber contractions by increasing the number of motor units contracting simultaneously. • Initially, with a weak signal from the CNS-only smaller units are stimulated. • Later, when signal from CNS becomes stronger, larger motor units are excited----This is called SIZE PRINCIPLE. Importance: It allows gradation of force to occur for weak & strong contractions. Cause: Smaller motor units are driven by smaller motor nerves & are more excitable than large ones---so are excited first! Then, if greater strength is required, then larger motor units are recruited.

29. 6. b: FREQUENCY SUMMATION Definitions: Force of contraction increases by increasing the frequency of contractions. Two twitches from 2 action potentials add together to produce greater tension in the fiber than produced by a single action potential. This is called twitch summation or frequency summation. • Force generated by the contraction of a single muscle fiber can be ↑ by increasing the rate at which the action potentials stimulate the muscle fiber. • If repeated APs are separated by long intervals of time, muscle fibers have time to relax completely between stimuli. • If interval of time between AP shortened, the Muscle fiber will not have relaxed completely at time of 2nd stimulus, resulting in a more forceful contraction.

30. A single action potential in a muscle fiber produces only a twitch. Let us see what happens when a second action potential occurs in a muscle fiber. If the muscle fiber has completely relaxed before the next action potential takes place, a second twitch of the same magnitude as the first occurs. The same excitation-contraction events take place each time, resulting in identical twitch responses. If, however, the muscle fiber is stimulated a second time before it has completely relaxed from the first twitch, a second action potential causes a second contractile response, which is added “piggyback” on top of the first twitch.

31. FREQUENCY SUMMATION When APs come one after the other after the relaxation of the muscle is complete……. When APs come one after the other before relaxation of the muscle is complete…

33. 6. b: FREQUENCY SUMMATION If APs continue to stimulate the muscle repeatedly at short intervals, there is no time for complete relaxation between contractions ↓ Individual twitches fuse into one continuous contraction ↓ Whole muscle contraction appears to be smooth, sustained & of maximal strength ↓ This is called TETANIZATION or TETANUS (A tetanic contraction is usually three to four times stronger than a single twitch.)

34. Physiologic basis of twitch summation & Tetanus: The main reason is the sustained elevation in cytosolic Ca2+ permitting greater cross-bridge cycling. As the frequency of action potentials increases, the duration of elevated cytosolic Ca2+concentration increases, and contractile activity likewise increases until a maximum tetanic contraction is reached. With tetanus, the maximum number of cross-bridge binding sites remain uncovered so that cross-bridge cycling, and consequently tension development, is at its peak.

35. 6.b: FREQUENCY SUMMATION & TETANUS Two types of Tetanus: • COMPLETE or FUSED TETANUS: If repeated stimuli are applied at fast rate, then no relaxation occurs between the stimuli, muscle reaches max. tension and remains there & a sustained contraction phase is obtained. • INCOMPLETE or UNFUSED TETANUS: if repeated stimuli at a slower rate, then muscle fiber relaxes slightly/incompletely between summated stimuli but the relaxation remains incomplete. CAUSE: Enough Ca2+ ions are maintained in the muscle sarcoplasm so that contractile state is sustained without allowing relaxation between AP.

38. 7. THE STAIRCASE/ TREPPE EFFECT • DEFINITION: When a series of maximal stimuli are delivered to the muscle at a frequency just below tetanizing frequency (when muscle twitch due to previous stimulus has just completed), the tension/amplitude developed during each twitch increases till a max. height is reached & a plateau is formed. This is called the Treppe/ staircase effect. Because the tension rises in stages, like the steps in a staircase, this phenomenon is called treppe, a German word meaning "stairs." • CAUSE:The rise is thought to result from a gradual increase in the concentration of calcium ions in the sarcoplasm, in part because the ion pumps in the sarcoplasmic reticulum are unable to recapture them in the time between stimulations.

39. Treppe Effect

40. 8. Isotonic vs. isometric contraction

41. ISOTONIC CONTRACTION There are two primary types of contraction, depending on whether the muscle changes length during contraction. They are: • Isotonic contraction: occurs when muscle contracts with shortening of length but against a constant load, thus, the tension on the muscle remains constant (iso= same, tonic= tension) OR A contraction that creates force & moves a load. Isotonic contractions are used for body movements and for moving external objects. E.g. picking up a book, a box.

42. ISOMETRIC CONTRACTION • Isometric contraction: occurs when muscle contracts without shortening in length. (iso= same, metric= measure or length) OR A contraction that creates force without movement. Isometric contractions can be seen in 2 cases: • If the object you are trying to lift is too heavy. • If the tension developed in the muscle is deliberately less than needed to move the load. E.g. standing for long time or holding up a glass of water while taking sips.

44. Physiologic basis of Isometric & Isotonic contractions: The same internal events occur in both isotonic and isometric contractions: Muscle excitation starts the sliding filament cycling; the cross bridges start cycling; and filament sliding shortens the sarcomeres, which exert force on the bone at the site of the muscle’s insertion. During a given time, a muscle may shift between isotonic & isometric contractions. E.g. when you lift a book up it is isotonic contraction and when you keep holding the book up while reading it is isometric contraction. NOTE: Since Work=Distance X Load, Isotonic contractions do work where as Isometric do not.

45. 9. ELECTROMYOGRAPHY • Activity of motor units can be studied by electromyography, the process of recording the electrical activities of the muscle on a cathode ray oscilloscope. • No anesthesia is required. Small metal discs are placed on the skin overlying the muscle as pick-up electrodes or hypodermic needle electrodes are used. • The record obtained with such electrodes is the Electromyogram (EMG).

47. 10. RECRUITMENT • If each motor unit contracts in an all-or-none manner, how then can muscle create graded contractions of varying force & duration? The answer lies in the fact that muscles are composed of multiple motor units of different types. This allows the muscle to vary contraction by: 1. Changing the types of motor units that are active OR 2. Changing the number of motor units that are responding at any one time. For a weak contraction of the whole muscle, only one or a few of its motor units are activated. For stronger & stronger contraction, more & more motor units are recruited. This is called Motor Unit Recruitment.

49. 10. RECRUITMENT • At rest EMG shows little or no activity • With minimum voluntary activity a few motor units discharge, & with increasing voluntary effort more & more are brought into play-----Recruitment of motor units • Asynchronous Recruitment: One way that CNS avoids fatigue in a sustained contraction The CNS alternates between the different motor units supplying the same muscle so that some of the motor units rest between contractions, preventing fatigue. e.g. during a sustained contraction, only a portion of the muscle’s motor units is involved as is necessary in muscles supporting the weight of the body against the force of gravity. The body alternates the motor units as shifts at a factory, to give the motor units that have been active an opportunity to rest while others take over. Changing of the shifts is carefully co-ordinated so that the sustained contraction is smooth rather than jerky.

50. 11. FAST vs SLOW FIBERS • The skeletal muscle fibers are mainly of 2 types: • SLOW or RED or TYPE I MUSCLE FIBERS • FAST or WHITE or TYPE II MUSCLE FIBERS • Every muscle of the bodyis composedof a mixture of both fast & slow fibers. • Simply: Fibers that react rapidly are Fast fibers & muscles that react slowly with long contractions are Slow fibers • Color is determined by the protein myoglobin