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Physiology of Muscle Tissue

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1 Physiology of Muscle Tissue
A Marvel of Movement!

2 Muscle Tissue Types Skeletal Smooth Cardiac- In the heart only.
Attached to bones Nuclei multiple and peripherally located During development, 100 or more myoblasts, a type of mesodermal cell, fuse to form a skeletal muscle fiber. Striated, Voluntary and involuntary (reflexes) Smooth Walls of hollow organs, blood vessels, eye, glands, skin Single nucleus centrally located Not striated, involuntary, gap junctions in visceral smooth Cardiac- In the heart only. Striations, involuntary, intercalated disks

3 Muscular System Functions
Body movement Maintenance of posture Respiration Production of body heat Communication Constriction of organs and vessels Heart beat

4 Properties of Muscle Contractility Excitability Extensibility
Ability of a muscle to shorten with force It DOES NOT produce force by lengthening/pushing! Excitability Capacity of muscle to respond to a stimulus Extensibility Muscle can be stretched to its normal resting length and beyond to a limited degree Elasticity Ability of muscle to recoil to original resting length after stretched

5 Cardiac Muscle Branching cells One/two nuclei per cell Striated
Involuntary Medium speed contractions Cardiac muscle tissue is only found in the heart. *Cardiac cells are arranged in a branching pattern. * Only one or two nuclei are present each cardiac cell. *Like skeletal muscle, cardiac muscle is striated. *Cardiac muscle is involuntary. *Its speed of contraction is not as fast as skeletal, but faster than that of smooth muscle.

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9 Smooth Muscle Fusiform cells One nucleus per cell Nonstriated
Involuntary Slow, wave-like contractions Smooth muscle is found in the walls of hollow organs. *Their muscle cells are fusiform in shape. *Smooth muscle cells have just on nucleus per cell. *Smooth muscle is nonstriated. *Smooth muscle is involuntary. *The contractions of smooth muscle are slow and wave-like.

10 Single-Unit Muscle Figure 12.35b
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.

11 Multi-Unit Muscle Figure 12.35a
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.

12 Multi vs. Single-Unit Muscle
Figure 12.35 Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.

13 Skeletal Muscle Long cylindrical cells Many nuclei per cell Striated
Voluntary Rapid contractions Skeletal muscle attaches to our skeleton. *The muscle cells a long and cylindrical. *Each muscle cell has many nuclei. *Skeletal muscle tissue is striated. It has tiny bands that run across the muscle cells. *Skeletal muscle is voluntary. We can move them when we want to. *Skeletal muscle is capable of rapid contractions. It is the most rapid of the muscle types.

14 Refresher Course in Muscle Physiology
Structural hierarchy of skeletal muscle 4/11/2003 Muscle A little less than half of the body’s mass is composed of skeletal muscle, with most muscles linked to bones by tendons through which the forces and movements developed during contractions are transmitted to the skeleton. Muscle fibers Muscle fiber Myofibril Sarcomere Modified from McMahon, Muscles, Reflexes and Locomotion Princeton University Press, 1984. EB2003--Susan Brooks

15 Muscle Proteins Contractile Proteins (actin and myosin)
Regulatory Proteins (i.e. tropomyosin and troponin) Structural Proteins (i.e. Titin)

16 Refresher Course in Muscle Physiology
4/11/2003 Myosin is a hexamer: 2 myosin heavy chains 4 myosin light chains C terminus 2 nm Coiled coil of two a helices Myosin is a molecular motor Myosin head: retains all of the motor functions of myosin, i.e. the ability to produce movement and force. Modified from Vander, Sherman, Luciano Human Physiology, McGraw-Hill. Myosin S1 fragment crystal structure Ruegg et al., (2002) News Physiol Sci 17: NH2-terminal catalytic (motor) domain neck region/lever arm Nucleotide binding site Catalytic domain responsible for binding & hydrolysis of ATP, and binding actin. Neck region responsible for transport of the load. Converter responsible for energy transduction. EB2003--Susan Brooks

17 Refresher Course in Muscle Physiology
4/11/2003 Hypothetical model of the swinging lever arm Working stroke produced by opening and closing of the nucleotide binding site, resulting in rotation of the regulatory domain (neck) about a fulcrum (converter domain). Sub-nanometer rearrangements at active site are geared up to give 5- 10 nm displacement at the end of the lever arm. Power Stroke Catalytic domain is attached to actin in a fixed position during the power stroke, whereas the conformation of the converter region changes significantly causing the swinging of the rigid lever arm. So in summary: Catalytic domain responsible for binding & hydrolysis of ATP, and binding actin. Neck region responsible for transport of the load. Converter responsible for energy transduction. Ruegg et al., (2002) News Physiol Sci 17: EB2003--Susan Brooks

18 Skeletal Muscle Produce movement Maintain posture & body position
Support Soft Tissues Guard entrance / exits Maintain body temperature Store nutrient reserves Makes up aprox. 40% of body weight

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20 Skeletal Muscle Structure
Organization of Connective Tissues Muscle attachments Endomysium, perimysium, and epimysium come together at ends of muscles to form connective tissue attachment to bone matrix i.e., tendon (bundle) or aponeurosis (sheet) Nerves Skeletal muscles are voluntary muscles, controlled by nerves of the central nervous system (brain and spinal cord) Blood Vessels Muscles have extensive vascular systems that 1) Supply large amounts of oxygen 2) Supply nutrients 3) Carry away wastes Skeletal Muscle fibers are: Are very long Develop through fusion of mesodermal cells (myoblasts) Become very large Contain hundreds of nuclei

21 -Sarcoplamsic Reticulum (SR): Fluid filled sacks that encircle each myofibril. It is similar to the smooth endoplasmic reticulum in other cells. -Terminal cisterns (cistern-reservoir): Dilated ends of SR, butt against T tubule from both sides. -T bubule and 2 terminal cisterns on either side of it form a TRIAD. -In relaxed muscle fiber, SR stores calcium ions -Release of calcium ions from terminal cisterns of SR triggers muscle contraction.

22 Skeletal Muscle Fiber Internal Organization of Muscle Fibers
The sarcolemma The cell membrane of a muscle fiber (cell) Surrounds the sarcoplasm (cytoplasm of muscle fiber) A change in transmembrane potential begins contractions Transverse tubules (T tubules) Transmit action potential through cell Allow entire muscle fiber to contract simultaneously Have same properties as sarcolemma Myofibrils Lengthwise subdivisions within muscle fiber Made up of bundles of protein filaments (myofilaments) Myofilaments are responsible for muscle contraction Types of myofilaments: thin filaments: made of the protein actin thick filaments: made of the protein myosin Sarcoplasmic reticulum (SR) A membranous structure surrounding each myofibril Helps transmit action potential to myofibril Similar in structure to smooth endoplasmic reticulum Forms chambers (terminal cisternae) attached to T tubules Triad Is formed by one T tubule and two terminal cisternae Cisternae: concentrate Ca2+ (via ion pumps) release Ca2+ into sarcomeres to begin muscle contraction

23 Connective Tissue, Nerve, Blood Vessels
External lamina Endomysium Perimysium Fasciculus Epimysium Fascia Nerve and blood vessels Abundant

24 -Some myoblasts (the cells that congegrate to form skeletal muscle fibers in the embryo) remain, they are referred to as satellite cells. -Satellite cells maintain (repair, etc.) skeletal muscle fibers. They can divide and they can fuse with one another and with muscle fibers to repair them, etc. -Mature muscle fibers range from between 10 to 100 micrometers in diameter. The “typical” muscle fiber is around 4 inches (10cm). There are muscle fibers that are up to a foot (30cm) long.

25 Embryologic origin:

26 -The plasma membrane of a muscle cell is referred to as the sarcolemma
-The plasma membrane of a muscle cell is referred to as the sarcolemma. The nuclei of skeletal muscle fibers lie just below the sarcolemma. -There are numerous invaginations of the sarcolemma that tunnel from the surface of the fiber to the center of the muscle fiber. They are open to the outside of the fiber and filled with interstitial fluid. These are called transverse tubules or T tubules. -Action potentials propagate along sarcolemma and T tubules, this insures a uniform contraction of a given muscle fiber. -Sarcoplasm: cytoplasm of the muscle fiber. -Glycogen is abundant in the sarcoplasmplasm that can quickly be split via hydrolysis into glucose which can be used to generate ATP.

27 -Myoglibin is also abundant in the sarcoplasm
-Myoglibin is also abundant in the sarcoplasm. Myoglobin is red in color. It is found only in muscle tissue. It binds free oxygen molecules that diffuse into muscle fibers from interstitial fluid, which obtained the free oxygen from the capillaries in the blood. -Mitochondria are abundant in muscle tissue. They lie very close to muscle proteins that utilize ATP during muscle contractions. -Myofibrils: contractile element of the skeletal muscle fibers. -They are about 2 micrometers in diameter and extend the entire length of the muscle fiber that they are in. -Myofibrils have prominent striations (stripes), thus the name “striated muscle tissue.” These striations make the entire muscle appear striated.

28 Striations:

29 Sarcomere Internal Organization of Muscle Fibers M Lines and Z Lines:
Sarcomeres The contractile units of muscle Structural units of myofibrils Form visible patterns within myofibrils Muscle striations A striped or striated pattern within myofibrils: alternating dark, thick filaments (A bands) and light, thin filaments (I bands) M Lines and Z Lines: M line: the center of the A band at midline of sarcomere Z lines: the centers of the I bands at two ends of sarcomere Zone of overlap: the densest, darkest area on a light micrograph where thick and thin filaments overlap The H Band: the area around the M line has thick filaments but no thin filaments Titin: Strands of protein reach from tips of thick filaments to the Z line stabilize the filaments

30 -Myofibrils are composed of filaments
-Myofibrils are composed of filaments. These are 1 to 2 micrometers long. The diameter of the THIN FILAMENTS is about 8 nanometers and those of the THICK FILAMENTS are around 16 nanometers. -In general, there are 2 thin filaments for each thick filament. -Filaments inside of the miofibril do not extend the entire muscle length. They are arranged in small compartments known as sarcomeres. These are the basic functional unit of the miofibril. -Z discs are narrow plate-shaped regions of dense material that separate sarcomeres from each other.

31 -Thick and thin filaments overlap one another to varying degrees
-Thick and thin filaments overlap one another to varying degrees. This is dependent on whether the muscle is contracted, relaxed or stretched. -The pattern of this overlap, that consists of a variety of zones and bands creates the striations that are characteristic of skeletal muscle.

32 Organization of myofilaments I:

33 Organization of myofilaments II:

34 Four Thin Filament Proteins
Sarcomere Function Transverse tubules encircle the sarcomere near zones of overlap Ca2+ released by SR causes thin and thick filaments to interact Muscle Contraction Is caused by interactions of thick and thin filaments Structures of protein molecules determine interactions Four Thin Filament Proteins F-actin (Filamentous actin) Is two twisted rows of globular G-actin The active sites on G-actin strands bind to myosin Nebulin Holds F-actin strands together Tropomyosin Is a double strand Prevents actin–myosin interaction Troponin A globular protein Binds tropomyosin to G-actin Controlled by Ca2+

35 Initiating Contraction
Ca2+ binds to receptor on troponin molecule Troponin–tropomyosin complex changes Exposes active site of F-actinThick Filaments Contain twisted myosin subunits Contain titin strands that recoil after stretching The mysosin molecule Tail: binds to other myosin molecules Head: made of two globular protein subunits reaches the nearest thin filament Myosin Action During contraction, myosin heads Interact with actin filaments, forming cross-bridges Pivot, producing motion Skeletal Muscle Contraction Sliding filament theory Thin filaments of sarcomere slide toward M line, alongside thick filaments The width of A zone stays the same Z lines move closer together

36 Sliding Filament Model I:
Actin myofilaments sliding over myosin to shorten sarcomeres Actin and myosin DO NOT change length Shortening sarcomeres responsible for skeletal muscle contraction During relaxation, sarcomeres lengthen

37 Z line M Lines and Z Lines: M line: the center of the A band
A small section of a myofibril is illustrated here. Note the thick myosin filaments are arranged between overlapping actin filaments. *The two Z lines mark the boundary of a sarcomere. The sarcomere is the functional unit of a muscle cell .We will examine how sarcomeres function to help us better understand how muscles work. A striped or striated pattern within myofibrils: alternating dark, thick filaments (A bands) and light, thin filaments (I bands) M Lines and Z Lines: M line: the center of the A band at midline of sarcomere Z lines: the centers of the I bands at two ends of sarcomere Zone of overlap: the densest, darkest area on a light micrograph where thick and thin filaments overlap The H Band: the area around the M line has thick filaments but no thin filaments

38 -Some components of muscle tissue are elastic
-Some components of muscle tissue are elastic. They stretch slightly before they transfer tension generated by sliding filaments. -Elastic components include titin molecules, connective tissue around muscle fibers (endomysium, perimysium and epimysium, as well as tendons.

39 -As skeletal muscles shorten, the elastic components are stretched and become taut. The tension then pulls the body part that it is attached to, resulting in movement. -Contractions do not always result in shortening of muscle fibers: Isometric contractions are where the myosin heads rotate and generate tension but thin filaments are unable to slide toward M line due to excessive opposing tension. Isotonic contractions result in the shortening of the muscle.

40 Sarcomere Relaxed Here is another diagram of a sarcomere. Note the A band. It is formed by both myosin and actin filaments. The part of the sarcomere with only actin filaments is called the I band. This is a sarcomere that is relaxed.

41 Sarcomere Partially Contracted
This sarcomere is partially contracted. Notice than the I bands are getting shorter.

42 Sarcomere Completely Contracted
The sarcomere is completely contracted in this slide. The I and H bands have almost disappeared.

43 Which filament has moved as the sarcomere contracted
Which filament has moved as the sarcomere contracted? Note the thick myosin filaments have not changed, but the thin actin filaments have moved closer together.

44 Sliding filament model II:

45 Sarcomere Shortening

46 Structure of Actin and Myosin

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48 The Ca ions bind to the troponin
This binding weakens troponin-tropomoysin complex and actin Troponin moiecule changes position, rolling the tropomyosin away from the active sites on actin Thus allowing them to interact with energized myosin heads

49 With the active sites on the actin exposed, the myosin heads bind to the, forming cross-bridges

50 After cross-bridge formation, the ATP present in the myosin is used to “cock” (the opposite direction from its resting state). As the ATP is used and the ADP + P is released, the “power stroke” occurs as the myosin pivots toward the M line.

51 When another ATP molecule attaches to the myosin head, the cross-bridge between the active site of the actin molecule and myosin head is broken. Thus freeing up the head to make another bridge and complete the contraction.

52 Myosin splits the ATP into ADP + P and uses the released energy to re-cock the myosin head (reaching forward). Cycle can be repeated endlessly as along as calcium ion concentration remain high and sufficient ATP is present. ATP produced in cells – aerobic vs. anaerobic Ca controlled by what?

53 Mechanism of muscle contraction

54 Summary of Muscle Contraction:
Ca 2+ ion is released from the SR CA 2+ bind to troponin Myosin cross-bridges bind to the actin The myosin head pivots towards the center of the sarcomere The myosin head binds an ATP molecule and detaches from the actin The free myosin head splits the ATP

55 Neuromuscular Junction
Is the location of neural stimulation Action potential (electrical signal) Travels along nerve axon Ends at synaptic terminal Synaptic terminal: releases neurotransmitter (acetylcholine or ACh) into the synaptic cleft (gap between synaptic terminal and motor end plate)

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57 The Neurotransmitter Acetylcholine or ACh
Travels across the synaptic cleft Binds to membrane receptors on sarcolemma (motor end plate) Causes sodium–ion rush into sarcoplasm Is quickly broken down by enzyme (acetylcholinesterase or AChE)

58 Function of Neuromuscular Junction

59 Five Steps of the Contraction Cycle
The influx of sodium will create an action potential in the sarcolemma. Note: This is the same mechanism for generating action potentials for the nerve impulse. The action potential travels down a T tubule. As the action potential passes through the sarcoplamic reticulum it stimulates the release of calcium ions. Calcium binds with troponin to move tropomyosin and expose the binding sites. Myosin heads attach to the binding sites of the actin filament and create a power stroke. ATP detaches the myosin heads and energizes them for another contraction. The process will continue until the action potentials cease. Without action potentials the calcium ions will return to the sarcoplasmic reticulum. Five Steps of the Contraction Cycle Exposure of active sites Formation of cross-bridges Pivoting of myosin heads Detachment of cross-bridges Reactivation of myosin

60 Free Ca2+ in the sarcoplasm triggers contraction
Relaxation Ca2+ concentrations fall Ca2+ detaches from troponin Active sites are re-covered by tropomyosin Sarcomeres remain contracted Skeletal muscle fibers shorten as thin filaments slide between thick filaments Free Ca2+ in the sarcoplasm triggers contraction SR releases Ca2+ when a motor neuron stimulates the muscle fiber Contraction is an active process Relaxation and return to resting length are passive

61 Single Fiber Tension The all–or–none principle
As a whole, a muscle fiber is either contracted or relaxed Tension of a Single Muscle Fiber Depends on The number of pivoting cross-bridges The fiber’s resting length at the time of stimulation The frequency of stimulation Length–tension relationship -Number of pivoting cross-bridges depends on: amount of overlap between thick and thin fibers -Optimum overlap produces greatest amount of tension: too much or too little reduces efficiency -Normal resting sarcomere length: is 75% to 130% of optimal length

62 Motor units Motor unit: Composed of one motor neuron and all the muscle fibers that it innervates There are many motor units in a muscle The number of fibers innervated by a single motor neuron varies (from a few to thousand) The fewer the number of fibers per neuron  the finer the movement (more brain power) Which body part will have the largest motor units? The smallest?

63 Recruitment (multiple motor unit summation)
Tension Produced by Whole Skeletal Muscles Depends on Internal tension produced by muscle fibers External tension exerted by muscle fibers on elastic extracellular fibers Total number of muscle fibers stimulated Motor units in a skeletal muscle Contain hundreds of muscle fibers That contract at the same time Controlled by a single motor neuron Recruitment (multiple motor unit summation) In a whole muscle or group of muscles, smooth motion and increasing tension are produced by slowly increasing the size or number of motor units stimulated Maximum tension Achieved when all motor units reach tetanus Can be sustained only a very short time

64 Motor Units: motor neuron and the muscle fibers it innervates
Spinal cord The smallest amount of muscle that can be activated voluntarily. Gradation of force in skeletal muscle is coordinated largely by the nervous system. Recruitment of motor units is the most important means of controlling muscle tension. Modified from Vander, Sherman, Luciano Human Physiology, McGraw-Hill. Since all fibers in the motor unit contract simultaneously, pressures for gene expression (e.g. frequency of stimulation, load) are identical in all fibers of a motor unit. To increase force: Recruit more M.U.s Increase freq. (force –frequency) From Matthews GG Cellular Physiology of Nerve and Muscle Blackwell Scientific Publications.

65 Physiological profiles of motor units:
all fibers in a motor unit are of the same fiber type Slow motor units contain slow fibers: Myosin with long cycle time and therefore uses ATP at a slow rate. Many mitochondria, so large capacity to replenish ATP. Economical maintenance of force during isometric contractions and efficient performance of repetitive slow isotonic contractions. Fast motor units contain fast fibers: Myosin with rapid cycling rates. For higher power or when isometric force produced by slow motor units is insufficient. Type 2A fibers are fast and adapted for producing sustained power. Type 2X fibers are faster, but non-oxidative and fatigue rapidly. 2X/2D not 2B. Modified from Burke and Tsairis, Ann NY Acad Sci 228: , 1974.

66 Muscle is plastic! Continuum of Physical Activity Load
Muscle “adapts” to meet the habitual level of demand placed on it, i.e. level of physical activity. Level of physical activity determined by the frequency of recruit- ment and the load. Increase muscle use – endurance training – strength training (cannot be optimally trained for both strength and endurance) Decrease muscle use – prolonged bed rest – limb casting – denervation – space flight. Frequency of recruitment Load inactivity controls strength trained endurance Continuum of Physical Activity Adapted from Faulkner, Green and White In: Physical Activity, Fitness, and Health, Ed. Bouchard, Shephard and Stephens Human Kinetics Publishers, 1994

67 Endurance training Control 12-weeks treadmill running
Little hypertrophy but major biochemical adaptations within muscle fibers. Increased numbers of mitochondria; concentration and activities of oxidative enzymes (e.g. succinate dehydrogenase, see below). Succinate dehy- drogenase (SDH) activity: Low activity light High activity dark Control 12-weeks treadmill running Images courtesy of John Faulkner and Timothy White

68 Disuse causes atrophy -- USE IT OR LOSE IT!
Individual fiber atrophy (loss of myofibrils) with no loss in fibers. Effect more pronounced in Type II fibers. “Completely reversible” (in young healthy individuals). ATPase activity: Type I fibers light Type II fibers dark Control Prolonged bed rest Images courtesy of John Faulkner

69 Tension Produced by Whole Skeletal Muscles
Sustained tension Less than maximum tension Allows motor units rest in rotation Muscle tone The normal tension and firmness of a muscle at rest Muscle units actively maintain body position, without motion Increasing muscle tone increases metabolic energy used, even at rest Back muscles 1:100 Finger muscles 1:10 Eye muscles 1:1

70 Muscle Contraction Types
Isotonic contraction Isometric contraction

71 Muscle Contraction Types
Isotonic contraction Isometric contraction Two Types of Skeletal Muscle Tension Isotonic Contraction Skeletal muscle changes length: resulting in motion If muscle tension > load (resistance): muscle shortens (concentric contraction) If muscle tension < load (resistance): muscle lengthens (eccentric contraction)

72 Muscle Contraction Types
Isotonic contraction Isometric contraction Two Types of Skeletal Muscle Tension Isometric contraction Skeletal muscle develops tension, but is prevented from changing length Note: iso- = same, metric = measure Produces no movement Used in Standing Sitting Posture

73 Action Potentials Phases All-or-none principle Propagate Frequency
Depolarization Inside plasma membrane becomes less negative Repolarization Return of resting membrane potential All-or-none principle Like camera flash system Propagate Spread from one location to another Frequency Number of action potential produced per unit of time

74 Excitation-Contraction Coupling
-Increasing levels of calcium ion (Ca2+) will start muscle contraction. Decreases will stop it. -Muscles at rest contain about 0.1 micromole per liter of calcium ion. -Much greater concentrations of calcium ion are stored in the SR. Concentrations may be 10,000x that of cytosol in relaxed muscle fiber. -As muscle action potentials propogate along the T tubles, calcium ion release channels in the SR are caused to open.

75 -When these channels are open, calcium ion flows into the cytosol of the muscle fiber.
-As a result of this, calcium ion concentrations rise 10x or greater. -Calcium ions bond with troponin and cause it to change shape. The troponin-tropomyosin complex moves a way from myosin-bonding sites on actin. -This allows the myosin heads to bond with the actin, thus the contraction cycle begins.

76 Excitation-Contraction Coupling
Mechanism where an action potential causes muscle fiber contraction Involves Sarcolemma Transverse or T tubules Terminal cisternae Sarcoplasmic reticulum Ca2+ Troponin

77 Action Potentials and Muscle Contraction

78 The SR membrane contains calcium active transport pumps which use ATP to move calcium ion out of cytosol, back into the SR. -After the last of the action potential moves through the T tubule, the active transport pumps clear most of the calcium ion out of the cytosol, thus the contraction cycle stops. -Calsequestrin, a substance which readily binds calcium ion, is present in the SR. This assists greatly in getting calcium ion out of the cytosol, which is key in stopping the contraction cycle. -This drop in calcium ion causes the troponin-tropomyosin complex to move back over the actin.

79 Muscle Twitch Muscle contraction in response to a stimulus that causes action potential in one or more muscle fibers Phases Lag or latent Contraction Relaxation

80 Muscle Length and Tension

81 Stimulus Strength and Muscle Contraction
All-or-none law for muscle fibers Contraction of equal force in response to each action potential Sub-threshold stimulus Threshold stimulus Stronger than threshold Motor units Single motor neuron and all muscle fibers innervated Graded for whole muscles Strength of contractions range from weak to strong depending on stimulus strength

82 Multiple Motor Unit Summation
A whole muscle contracts with a small or large force depending on number of motor units stimulated to contract

83 Multiple-Wave Summation
As frequency of action potentials increase, frequency of contraction increases Action potentials come close enough together so that the muscle does not have time to completely relax between contractions.

84 Incomplete tetanus Muscle fibers partially relax between contraction
There is time for Ca 2+ to be recycled through the SR between action potentials

85 Treppe Graded response Occurs in muscle rested for prolonged period
Each subsequent contraction is stronger than previous until all equal after few stimuli

86 ATP as Energy Source ATP or adenosine triphosphate is the form of energy that muscles and all cells of the body use. *The chemical bond between the last two phosphates has just the right amount of energy to unhook myosin heads and energize them for another contraction. Pulling of the end phosphate from ATP will release the energy. ADP and a single phosphate will be left over. New ATP can be regenerated by reconnecting the phosphate with the ADP with energy from our food.

87 Molecule capable of storing ATP energy
Creatine Molecule capable of storing ATP energy Creatine + ATP Creatine phosphate + ADP Creatine is a molecule capable of storing ATP energy. It can combine with ATP to produce creatine phosphate and ADP. The third phosphate and the energy from ATP attaches to creatine to form creatine phosphate. When needed again, the reaction is reversed and facilitated by enzyme creatine phosphokinase (CPK or CK). When cell muscles are damaged, this leaks across capillary beds and into the blood stream. Thus a high blood concentration of CPK is indicative of muscle tissue injury ADP + Creatine phosphate ATP + Creatine

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89 Metabolism Aerobic metabolism Anaerobic metabolism 95% of cell demand
Kreb’s cycle 1 pyruvic acid molecule  17 ATP Anaerobic metabolism Glycolysis  2 pyruvic acids + 2 ATP Provides substrates for aerobic metabolism As pyruvic acid builds converted to lactic acid Muscle fatigue is often due to a lack of oxygen that causes ATP deficit. Lactic acid builds up from anaerobic respiration in the absence of oxygen. Lactic acid fatigues the muscle.

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93 Muscle Fatigue Muscle Fatigue Results of Muscle Fatigue The Cori Cycle
When muscles can no longer perform a required activity, they are fatigued Results of Muscle Fatigue Depletion of metabolic reserves Damage to sarcolemma and sarcoplasmic reticulum Low pH (lactic acid) Muscle exhaustion and pain The Recovery Period The time required after exertion for muscles to return to normal Oxygen becomes available Mitochondrial activity resumes The Cori Cycle The removal and recycling of lactic acid by the liver Liver converts lactic acid to pyruvic acid Glucose is released to recharge muscle glycogen reserves Oxygen Debt After exercise or other exertion The body needs more oxygen than usual to normalize metabolic activities Resulting in heavy breathing

94 Fatigue Decreased capacity to work and reduced efficiency of performance Types: Psychological Depends on emotional state of individual Muscular Results from ATP depletion Synaptic Occurs in neuromuscular junction due to lack of acetylcholine

95 Slow and Fast Fibers Slow-twitch or high-oxidative
Contract more slowly, smaller in diameter, better blood supply, more mitochondria, more fatigue-resistant than fast-twitch Fast-twitch or low-oxidative Respond rapidly to nervous stimulation, contain myosin to break down ATP more rapidly, less blood supply, fewer and smaller mitochondria than slow-twitch Distribution of fast-twitch and slow twitch Most muscles have both but varies for each muscle Effects of exercise Hypertrophies: Increases in muscle size Atrophies: Decreases in muscle size

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97 Oxidative and Glycolative Fibers

98 Muscle Fatigue

99 Muscle Hypertrophy Muscle growth from heavy training
Increases diameter of muscle fibers Increases number of myofibrils Increases mitochondria, glycogen reserves Hypertrophy is the enlargement of a muscle. Hypertrophied muscles have more capillaries and more mitochondria to help them generate more energy. Strenuous exercise and steroid hormones can induce muscle hypertrophy. Since men produce more steroid hormones than women, they usually have more hypertrophied muscles.

100 Muscle Atrophy Lack of muscle activity
Reduces muscle size, tone, and power

101 Steroid Hormones Stimulate muscle growth and hypertrophy
Growth hormone Testosterone Thyroid hormones Epinephrine Growth hormone & testosterone – stimulate synthesis of contractile proteins & enlargement of skeletal muscles Thyroid hormones – elevate rate of energy consumption in resting & active skeletal muscles Epinephrine – stimulate muscle metabolism and increase the duration of stimulation and force of contraction

102 Muscle Tonus Tightness of a muscle Some fibers always contracted
Muscle tonus or muscle tone refers to the tightness of a muscle. In a muscle some fibers are always contracted to add tension or tone to the muscle.

103 Tetany Sustained contraction of a muscle
Result of a rapid succession of nerve impulses Tetany is a sustained contraction of a muscle. It results from a rapid succession of nerve impulses delivered to the muscle.

104 Tetanus This slide illustrates how a muscle can go into a sustained contraction by rapid neural stimulation. In number four the muscle is in a complete sustained contraction or tetanus.

105 Refractory Period Brief period of time in which muscle cells will not respond to a stimulus The refractory period is a brief time in which muscle cells will not respond to stimulus.

106 Refractory The area to the left of the red line is the refractory period for the muscle contraction. If the muscle is stimulated at any time to the left of the line, it will not respond. However, stimulating the muscle to the right of the red line will produce a second contraction on top of the first contraction. Repeated stimulations can result in tetany.

107 Refractory Periods Skeletal Muscle Cardiac Muscle
Cardiac muscle tissue has a longer refractory period than skeletal muscle. This prevents the heart from going into tetany. Skeletal Muscle Cardiac Muscle

108 Smooth Muscle Contraction

109 Additional Smooth Muscle Info
Smooth muscle contractions start more slowly and last longer than those of skeletal muscle No T tubules, therefor it takes Ca+ longer to get to fibers. Ions flow in from instertial fluid and S.R. Regulatory proteins that cause this are different from skeletal muscles

110 …Continued This accounts for the smooth muscle tone that is important in places such as the GI tract, the walls of the blood vessels, etc. where steady pressure is important. Smooth muscles contract in response to action potentials from the autonomic nervous system.

111 …Continued Other factors that result in smooth muscle contraction include stretching, hormones, changes in pH, changes in free oxygen and carbon dioxide levels and ion concentrations. Smooth muscle is able to stretch much more than skeletal muscle while maintaining its ability to contract.

112 …Continued When smooth muscle fibers stretch, they initially contract and develop increased tension, after about one minute the tension decreases. This is called the stress relaxation response. This allows smooth muscles to undergo great changes in length while maintaining the ability to contract.

113 …Continued The stress relaxation response is very important in organs such as the bladder and stomach. These organs stretch when full yet the muscle rebounds when the organ is emptied and the muscle (organ) retains its firmness.

114 Regeneration Smooth muscle has greatest capacity of the 3 types of muscle tissue to regererate. Hypertrophy: growth due to enlargement of existing cells Hyperplasia: growth due to the increase of the number of cells. Skeletal muscles seem to only undergo hypertrophy.

115 …Continued Cardiac muscles seem to only undergo hypertrophy.
Smooth muscles can undergo hypertrophy and some retain their ability to undergo hyperplasia (i.e. uterine muscle fibers may retain their ability to divide). Pericytes are stem cells that facilitate hyperplasia in capillaries and small veins.

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117 Electrical Properties of Smooth Muscle

118 Cardiac muscle -similar in arrangement of actin and myosin, Z discks, etc. -Cardiac muscle fibers contain intercalcated discks: they are transverse thickenings of the sarcolemma that eonncet ends of cardiac muscle fibers to one antoher    -these contain desmosomes which hold fibers together    -these also contain gap junctions which allow action potentials to spread from    one fiber to another, thus cardiac muscle fibers needn't be stimulate driectly    from neuron as skeletal muscles -cardiac muscle fibers contain midochondria that are larger than those in skeletal muscle fibers, evidence that the heart relies very much on aerobic cellular respiration -cardiac muscle fibers can use lactic acid fibers produced by skeletal muscle to make ATP (very useful during exercise)

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