THE MUSCULAR SYSTEM: SKELETAL MUSCLE TISSUE AND MUSCLE ORGANIZATION

1. THE MUSCULAR SYSTEM: SKELETAL MUSCLE TISSUE AND MUSCLE ORGANIZATION

5. Muscle Tissue: Functions • 1. producing body movements • integrated action of skeletal muscle, joints and bones • 2. stabilizing body positions • skeletal muscle contraction stabilizes joints and bones • postural muscles contract continuously when awake • 3. storing and moving substances in the body • contraction of ring-like smooth muscle sphincters – storage of material in an organ • storage of glucose within skeletal muscle • movement of blood by cardiac muscle and by smooth muscle within the blood vessels • movement of food through the GI tract by smooth muscles within abdominal viscera

6. Properties of Muscles Electrical excitability -ability to respond to stimuli by producing electrical signals such as action potentials -two types of stimuli: 1. autorhythmic electrical signals 2. chemical stimuli Contractility -ability to contract when stimulated by an AP -isometric contraction: tension develops, length doesn’t change -isotonic contraction: tension develops, muscle shortens Extensibility -ability to stretch without being damaged -allows contraction even when stretched Elasticity -ability to return to its original length and shape

7. Gross Anatomy • muscle is wrapped in a protective fascia • -fascia = sheet of fibrous connective tissue • that supports and surrounds muscle or organs • a superficial fascia separates muscle from the overlying skin • -also known as the subcutaneous layer • -made up of areolar tissue and adipose tissue • -provides support for blood vessel and nerves • -the adipose tissue stores most of the body’s triglycerides • and provides insulation • muscles with similar functions are grouped and held together by layers of deep fascia • -dense irregular connective tissue • -allow free movement of muscles, carries nerves, BVs

8. Gross Anatomy • muscles are really groups of • fascicles • the fascicles are groups of muscle fibers = considered to be an individual muscle cell • three layers of connective tissue extend from the deep fascial layer • Epimysium • Perimysium • Endomysium • these layers further strengthen and protect muscle • outermost layer = epimysium • encircles the entire muscle • next layer = perimysium • surrounds groups of 10 to 100 individual muscle fibers • separates them into bundles = fascicles • give meat its “grain” because the fascicles are visible • both epimysium and perimysium are dense irregular connective tissue

9. penetrating the fasicles and separating them into individual muscle fibers = endomysium (areolar connective tissue) • all three of these connective tissue layers extend beyond the muscle • and attaches it to other structures • -called a tendon = cord of regular dense CT that attaches • a muscle to the periosteum of bone • when the CT extends as a broad flat sheet = aponeurosis • the muscle fiber is made up • of fused muscle cells • -these muscle cells have a unique cytoskeleton • made up of myofibrils • each myofibril is comprised of • repeating units of protein filaments = sarcomeres

10. generally muscles are supplied with one artery and two veins • they accompany the nerve • nerves that induce muscle contraction = somatic motor neurons (part • of the somatic division of the PNS) • communication between muscle and these neurons • Neuromuscular junction(NMJ) • at the NMJ the neuron ends at an axon terminal with synaptic bulbs for • the release of neurotransmitters -> contraction

11. Microanatomy of Muscle Fibers • New terminology • Cell membrane = sarcolemma • Cytoplasm = sarcoplasm • Internal membrane system = sarcoplasmic reticulum

12. Muscle Cell Anatomy • Transverse tubules • Invaginations of sarcolemma • Carry electrical impulses • Myofibrils within sarcoplasm • Protein filaments • Sarcomeres – organized arrangement • Myofilaments form myofibrils • Thin filaments (actin, troponin, tropomyosin) • Thick filaments (myosin)

13. Microanatomy of Muscle Fibers • New terminology • Cell membrane = sarcolemma • Cytoplasm = sarcoplasm • Internal membrane system = sarcoplasmic reticulum • Large, multinucleated cells • embryonic development - muscle fibers arise from fusion of a hundred or more mesodermal cells called myoblasts – organized into muscle fibers composed of myofibrils • once fused, these muscle cells lose the ability of undergo mitosis - number of muscle cells predetermined before birth

14. Microanatomy of Muscle Fibers • muscle fibers are bound by a plasma membrane = sarcolemma • thousands of tiny invaginations in this sarcolemma called T or transverse • tubules - tunnel in toward the center of the cell • -T tubules are open to the outside of the fiber - continuous with • the sarcolemma • - filled with interstitial fluids • action potentials travel along the sarcolemma and the T tubules • - allows for the even and quick spread of an action potential • the cytoplasm is called a sarcoplasm • -substantial amounts of glycogen - can be broken into glucose • -contains myoglobin - binds oxygen needed for muscle ATP • production

15. Microanatomy of Muscle Fibers • contractile elements of the muscle fibrils = myofilaments • -2 microns in diameter • -comprised of actin or myosin • -give the muscle its striated appearance • fibers have a system of fluid-filled membranes = sarcoplasmic • reticulum • -encircles each myofibril • -similar to the ER • -have dilated end sacs = terminal cisterns • -stores calcium when at rest - releases it during contraction • -release is triggered by an AP

16. M line Sarcomere Structure • sarcomere = regions of myosin (thick myofilament) and actin (thin myofilament) • bounded by the Z line (actinin) • actin filaments project out from Z line • myosin filaments lie in center of sarcomere - overlap with actin and connect • via cross-bridges • myosin only region = H zone • myosin filaments are held in place by the M line proteins. • actin region = I band • length of myosin filaments = A band • contraction = “sliding filament theory” • -actin and myosin myofilaments slide over each other and sarcomere shortens

17. The Proteins of Muscle • Myofibrils are built of 3 kinds of proteins • contractile proteins • myosin and actin • regulatory proteins which turn contraction on & off • troponin and tropomyosin • structural proteins which provide proper alignment, elasticity and extensibility • titin, myomesin, nebulin and dystrophin

18. Structural proteins of muscle • Nebulin, an inelastic protein helps align the thin filaments. • Dystrophin links thin filaments to sarcolemma and transmits the tension generated to the tendon. • Titin anchors thick filament to the M line and the Z line. • -the portion of the molecule between the Z line and the end of the thick filament can stretch to 4 times its resting length and spring back unharmed. • -has a role in recovery of the muscle from being stretched.

19. Contractile proteins of muscle • actin filament is associated with troponin and tropomyosin • the myosin-binding site on each actin molecule is covered by tropomyosin in relaxed muscle • myosin thick myofilament is a bundle of myosin molecules • -each myosin protein has 2 globular “heads” each with a site to bind ATP and to bind actin

20. Contraction: The Sliding Filament Theory • Contraction: • Active process • Elongation is passive • Amount of tension produced is proportional to degree of overlap of thick and thin filaments • SF Theory: • Explains how a muscle fiber exerts tension • Four step process • Active sites on actin • Crossbridge formation • Cycle of attach, pivot, detach, return • Troponin and tropomyosin control contraction

22. -calcium binds to troponin and exposes sites that can interact with myosin - Ca+2 binds to troponin & causes troponin-tropomyosin complex to move & reveal myosin binding sites on actin -ATP binding, hydrolysis and ADP release changes the conformation of the head (“power stroke”) and causes actin to “slide” along the myosin myofilaments -shortens the distance between the Z lines

24. Sarcoplasmic Reticulum and Calcium release • the SR wraps around each A and I band • segmented with T-tubules between each SR segment • each segment forms saclike regions at the ends = lateral sacs • between the lateral sac and the T-tubule is an orderly arrangement of proteins = foot proteins (ryanodine receptors) • these foot proteins bridge the gap between SR and T-tubule • serve as Ca release channels • 50% of the foot proteins of the SR are “zipped” together with similar proteins found on the T-tubule (dihydropyridine receptors) • the T-tubule receptors respond to changes in voltage – voltage-gated sensors • when an AP travels down the T-tubule – the local depolarization activates these sensors which then open the foot proteins on the SR • the opening of these foot proteins triggers the SR to open the remaining foot proteins that are not connected to the T-tubule • efflux of calcium into the sarcoplasm

25. The Neuromuscular Junction • end of neuron (synaptic terminal or axon bulb) is in very close association • with a single muscle fiber (cell) • nerve impulse leads to release of neurotransmitter(acetylcholine) from the synaptic end terminal • AcH binds to receptors on myofibril surface (ligand-gated Na channels) • binding leads to influx of sodium ions and depolarization of the membrane potential of the sarcolemma • creation of an action potential that travels through the muscle cell – eventual contraction • Acetylcholinesterase breaks down ACh • Limits duration of contraction

26. Muscle Contraction: A summary • called excitation-contraction coupling – describes the events linking generation of an AP (excitation) to the contraction of the muscle • ACh released from synaptic vesicles at each neuromuscular junction • Binding of ACh to motor end plate (muscle cell of the NMJ) • entrance of Na ions and depolarization • Generation of electrical impulse in sarcolemma • action potential • Conduction of impulse along T-tubules • AP flows along the outside of the muscle cell via the sarcolamma • also enters the inside of the muscle cell via T-tubules • close association of T-tubules with the sarcoplasmic reticulum (SR) • Release of Calcium ions by SR • AP results in release of Ca by the SR • SR is in close physical association with each A and I band • Ca binds to troponin and “pulls it away” from the actin filament • Exposure of active sites on actin • Cross-bridge formation with myosin • Formation of ATP by the muscle cell • sliding filaments & contraction

27. The Events in Muscle Contraction

28. Relaxation • Acetylcholinesterase (AChE) breaks down ACh within the synaptic cleft • Muscle action potential ceases • Ca+2 release channels (foot proteins) close • Active transport pumps Ca2+ back into storage in the sarcoplasmic reticulum • Ca ATPase pumps • the rate of pumping Ca back into the SR is slower than the rate of efflux • so as long as the muscle is being stimulated via the T-tubules – more Ca in the sarcoplasm • Calcium-binding protein (calsequestrin) helps hold Ca+2 in SR • enables more calcium to be stored in the SR • calcium concentration is 10,000 more concentrated in the SR than in the sarcoplasm • Tropomyosin-troponin complex recovers binding site on the actin

29. Rigor Mortis • Rigor mortis is a state of muscular rigidity that begins 3-4 hours after death and lasts about 24 hours • After death, Ca+2 ions leak out of the SR and allow myosin heads to bind to actin • Since ATP synthesis has ceased, crossbridges cannot detach from actin until proteolytic enzymes begin to digest the decomposing cells.

30. Length of Muscle Fibers: Length Tension relationship • Normally • resting muscle length remains between 70 to 130% of the optimum • Optimal overlap of thick & thin filaments • produces greatest number of crossbridges and the greatest amount of tension • optimal length = lo (muscle length at which maximum force is generated) • optimal length = point A • As stretch muscle (past optimal length) • length of the muscle fiber is greater than lo • fewer cross bridges exist & less force is produced = point B • when muscle is stretched to about 70% than lo of its (point C) the actin filaments are completely pulled out from between the myosin – no cross-bridges possible • If muscle is overly shortened (less than optimal) • length of the muscle fiber is less than lo • thick filaments crumpled by Z discs and the actin filaments overlap – poor cross-bridge formation • fewer cross bridges exist & less force is produced = point D • even less calcium released from the SR - ?? A B D C

31. Levers

32. Motor Units • Each skeletal fiber has only ONE NMJ • MU = Somatic neuron + all the skeletal muscle fibers it innervates • Number and size indicate precision of muscle control • Muscle twitch • Single momentary contraction in one muscle fiber • too small to generate any significant force • Response to a single stimulus • All-or-none theory • Either contracts completely or not at all • Motor units are grouped together to provide a greater force • in a whole muscle fire asynchronously • -some fibers are active others are relaxed • -delays muscle fatigue so contraction can be sustained • Muscle fibers of different motor units are intermingled so that net distribution of force applied to the tendon remains constant even when individual muscle groups cycle between contraction and relaxation.

33. Neural control of Motor Units • 1. input from afferent neurons • at the level of the SC • by interneurons within the SC = spinal reflex • afferent information is needed to control skeletal muscle activity • the CNS must know the position of your body prior to initiating movement and must know how the movement is progressing = prioprioceptive input • comes from information from your eyes, joints, inner ear and from the muscles themselves (prioprioceptors) • muscle spindles and tendon organs within the muscle monitor changes in muscle length and tension (see lecture 9) • 2. input from the motor cortex • fibers originating from neuronal cell bodies within the primary motor cortex = pyramidal cells • descend directly (as one continuous axon) to synapse with motor neurons in the SC • part of the corticospinal motor system (lecture 8) • 3. input from the brain stem • extrapyramidal motor system • involves many regions of the brain • final link is the brain stem

34. 1. muscle spindles • monitor changes in muscle length • used by the brain to set an overall level of involuntary muscle contraction = motor tone • consists of several sensory nerve endings that wrap around specialized muscle fibers = intrafusal muscle fibers • very plentiful in muscles that produce very fine movements – fingers, eyes • stretching of the muscle stretches the intrafusal fibers, stimulating the sensory neurons – info to the CNS • IFMs also receive incoming information from gamma motor neurons – end near the IFMs and adjust the tension in a muscle spindle according to the CNS • also have extrafusal muscle fibers which are innervated by alpha motor neurons • response to a stretch reflex • 2. tendon organs • located at the junction of a tendon and a muscle • protect the tendon and muscles from damage due to excessive tension • consists of a thin capsule of connective tissue enclosing a few bundles of collagen • penetrated by sensory nerve endings that intertwine among the collagen fibers

35. Motor Tone • Resting muscle contracts random motor units • Constant tension created on tendon • Resting tension – muscle tone • Stabilizes bones and joints

36. Muscle Metabolism • Production of ATP: • -contraction requires huge amounts of ATP • -muscle fibers produce ATP three ways: • 1. Creatine phosphate • 2. Aerobic metabolism • 3. Anaerobic metabolism

37. Creatine Phosphate • Muscle fibers at rest produce more ATP then they need for resting metabolism • Excess ATP within resting muscle used to form creatine phosphate or phosphocreatine • Creatine phosphate: 3-6 times more plentiful than ATP within muscle • the first storehouse of energy used upon the onset of contraction when additional ATP is needed • Its quick breakdown provides energy for creation of ATP • Sustains maximal contraction for 15 sec (used for 100 meter dash) • or about 8 muscle twitches • creatine phosphate breakdown is favored by muscles undergoing explosive movements • Athletes tried creatine supplementation • gain muscle mass but shut down bodies own synthesis (safety?)

38. Aerobic Cellular Respiration • Muscles deplete creatine – make ATP in anaerobically or aerobically • aerobic respiration produces ATP for any activity lasting over 30 seconds • if sufficient oxygen is available, pyruvic acid enters the mitochondria to generate ATP, water and heat via the electron transport chain • fatty acids and amino acids can also be used by the mitochondria • Provides 90% of ATP energy if activity lasts more than 10 minutes • also can keep pace with moderate activities like walking • Each glucose = 36 ATP • Fatty acids = ~100 ATP • Sources of oxygen – diffusion from blood, released by myoglobin (hemoglobin-like molecule of muscle cells)

39. Anaerobic Cellular Respiration • Muscles deplete creatine – make ATP in anaerobically via glycolysis only • Glycogen converted into glucose • normally ATP produced from the breakdown of glucose into pyruvic acid during glycolysis and this enters the citric acid cycle and electron transport chain to make ATP • if insufficient oxygen is present glycolysis creates the products for oxidative phosphorylation • glucose is broken down into two pyruvic acid molecules to yield 2 ATP • BUT in low oxygen this pyruvic acid is further processed to yield more ATP • by-product = lactic acid • Glycolysis can continue anaerobically to provide ATP for 30 to 40 seconds of maximal activity (200 meter race) http://www.indstate.edu/thcme/mwking/oxidative-phosphorylation.html

41. Muscle Fatigue • Inability to contract after prolonged activity • central and peripheral fatigue • central fatigue is feeling of tiredness and a desire to stop (protective mechanism) • Factors that contribute to muscle fatigue • depletion of creatine phosphate • decline of Ca+2 within the sarcoplasm • insufficient oxygen or glycogen • accumulation of extracellular K ions • drop in pH within muscle cell • buildup of lactic acid • buildup of ADP and inorganic phosphate from ATP hydrolysis • insufficient release of acetylcholine from motor neurons

42. Isotonic and Isometric Contraction • Isotonic contractions = a load is moved • concentric contraction = a muscle shortens to produce force and movement • eccentric contractions = a muscle lengthens while maintaining force and movement • Isometric contraction = no movement occurs • tension is generated without muscle shortening • maintaining posture & supports objects in a fixed position

43. Atrophy • wasting away of muscles • caused by disuse (disuse atrophy) or severing of the nerve supply (denervation atrophy) • the transition to connective tissue can not be reversed • Hypertrophy • increase in the diameter of muscle fibers • resulting from very forceful, repetitive muscular activity and an increase in myofibrils, SR & mitochondria

44. Exercise-Induced Muscle Damage • Intense exercise can cause muscle damage • electron micrographs reveal torn sarcolemmas, damaged myofibrils an disrupted Z discs • increased blood levels of myoglobin & creatine phosphate found only inside muscle cells • Delayed onset muscle soreness • 12 to 48 Hours after strenuous exercise • stiffness, tenderness and swelling due to microscopic cell damage

45. Three Types of Muscle Fibers • Fast fibers = fast twitchglycolytic • Slow fibers = slow twitchoxidative • 10 times slower than fast fibers • Intermediate fibers = fast twitch oxidative glycolytic • Fibers of one motor unit all the same type • Percentage of fast versus slow fibers is genetically determined • Proportions vary with the usual action of the muscle • - neck, back and leg muscles have a higher proportion of postural, slow oxidative fibers • - shoulder and arm muscles have a higher proportion of fast glycolytic fibers

46. Fast Fibers • Large in diameter • Contain densely packed myofibrils • Large glycogen reserves • high ATPase activity – faster cross-bridge potential • Fast oxidative-glycolytic (fast-twitch A) (intermediate fibers) • red in color (lots of mitochondria, myoglobin & blood vessels) • higher ability to produce ATP via aerobic metabolism • highly vascularized • split ATP at very fast rate; used for walking and sprinting • Fast glycolytic (fast-twitch B) • white in color (few mitochondria & BV, low myoglobin) • higher concentration of enzymes for glycolysis • need less oxygen to function • anaerobic movements for short duration; used for weight-lifting • fatigue faster than fast-twitch A fibers

47. Slow fibers • Half the diameter of fast fibers • Three times longer to contract • low ATPase activity, low glycogen content • high resistance to fatigue • higher ability to produce ATP via aerobic metabolism • many mitochondria • highly vascularized • Continue to contract for long periods of time • e.g. marathon runners

49. Muscle Adaptation • long-term adaptive changes can occur with exercise depending on the pattern of neuronal discharge • 1. improvement of oxidative capacity • regular aerobic activity • induces metabolic changes in the oxidative fibers • increases number of mitochondria and capillaries to the fast and slow oxidative fibers • more efficient use of oxygen – prolonged activity without fatigue • 2. muscle hypertrophy • increased by regular bursts of short, anaerobic, high-intensity exercise • increases the diameter of the muscle fiber – increase synthesis of myosin and actin • exercise triggers the activation of specific genes that direct the synthesis of actin and myosin • also a role for muscle stem cells? • 3. influence of testosterone • makes muscle fibers thicker • promotes the synthesis of myosin and actin

50. Smooth muscle • slowest of contraction and relaxation of all three types of muscle • lowest O2 consumption rates • require less energy to contract • generates force over longer periods of time • maximum tension with only 25-30% of cross-bridges “active” • can still generate tension even when over-stretched • the nonstretched length of smooth muscle is shorter than skeletal • therefore it can be stretched quite a distance before the optimal length is reached • important for the contractile ability of hollow organs and blood vessels