L ia D am ayanti. D epartm ent of H istology Faculty of M edicine University of I ndonesia

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L ia D am ayanti D epartm ent of H istology Faculty of M edicine University of I ndonesia 1

Introduction M uscle tissue One of the four basic tissues Properties Contractility Converting chemical energy into mechanical work 2

Introduction The main function of skeletal muscle Positioning of the skeleton M ovement of the skeleton M uscle tissue attach firmly to related bone M uscle contraction moves the skeletons 3

through skeletal muscle contraction that produce muscle tension 4

D evelopment D erived from mesoderm Somatic mesoderm Splanchnic mesoderm Skeletal muscle Smooth muscle Splanchnopleuric mesoderm Cardiac muscle 5

Terminology in muscle Sarcolemma Sarcoplasm Smooth endoplasmic reticulum in the muscle cell Sarcosomes Cytoplasm of muscle cell Sarcoplasmic reticulum M uscle cell membrane The mitochondria of muscle cell M uscle fiber M uscle cell L onger than wide L iving entity 6

M uscle types 3 types of muscle: Skeletal muscle Smooth muscle Cardiac muscle 7

S keletal M uscle Striated muscle Regular alterantinf light and dark cross striations M ost of voluntary muscle mass of the body 8

S keletal M uscle Organization A n anatomically named muscle A group of muscle bundles or fascicles Surrounded by epimysium (connective tissue) Fascicle (muscle bundle) Consists of a variable number muscle fibers D elineated or surrounded by perimysium The connective tissue of epimysium that extend inward, surrounding the muscle bundle 9

S keletal M uscle M uscle fiber The basic structural unit A long, cylindrical and multinucleate structure Surrounded by endomysium The connective tissue of perimysium that extend inward, surrounding the muscle fiber 10

Light M icroscopy Appearance M uscle fiber A long, cylindrical and multinucleated structure The nuclei L ocated in the periphery of the muscle fiber Contact with sarcolemma In the HE Staining L ight and dark transverse crossbands D ark stained bands: A bands L ight stained bands: I bands 11

S k eleta l M us c le U nit Organization unit Sarcolemma Conduction of nerve impulse to the muscle fibers Sarcoplasmic reticulum Control movement of skeletal muscle M yofibriles Contraction of skeletal muscle Contractile unit Sarcomere Region of myofibril between 2 successive Z disk 12

Ultrastructure Sarcolemma Similar to other cell with some differences Continued within skeletal muscle fiber as T tubules T-tubule: A long tubule extending inward from the sarcolemma L ie at the junction of the A and I bands (2 sets of T-tubule in each sarcomere) Facilitate the conduction of waves of depolarization along the sarcolemma 13

Ultrastructure Sarcoplasmic reticulum A membrane bounded tubules forms a continuous network Occupying the narrow spaces between the myofibrils forms a meshwork around each myofibril and display dilated terminal cisternae at each A -I junction A triad T tubule is flanked by two cisternae A wave of depolarization will spread from the surface of sarcolemma throughout the T-tubule reaching the terminal cisternae which has the voltage-gated Ca2+ release channel 14

Ultrastructure M itochondria located just deep to the sarcoplasm numerous M yofibril held in register with each other by the intermediate filament desmin and vimentin the bundles of myofibril attached to the cytoplasmic aspect of the sarcolemma by various protein including dystrophin 15

M yofibril The arrangement of thick and thin filament A specific and constan relationship Each thick filament is surrounded by six thin filaments arranged in hexagonal pattern 16

O rganization of M yofibril Thick Filament 15 nm in diameter and 1.5 um long Form parallel arrays interdigitating with the thin filament Composed of myosin Consists of 200-300 myosin molecules bundle together One half of the molecules have their heads pointing toward the opposite end This arrangement result in a bare zone in the center of the A band where there are no myosin heads 17

Thick Filament Composed of two identical heavy chain and two pairs of light chains 18

Thick Filament Heavy chains Two golf clubs Rod like polypeptide chains wrapped around each other in an α helix Rod like tail light meromyosin Cleaved by trypsin Heavy meromyosin Can be cleaved by papain Two globular subfragment Binds ATP Function in the formation of cross-bridges between thick and thin myofilaments A short helical rod like subfragment 19

Thick Filament Heavy chains Has two hinges Junction of the L M M and HM M The neck region near the two globular heads Each heavy chain has two light chains L ight chains Two type One of each associated with the S1 sub-fragment 20

O rganization of M yofibril Thin Filament 7 nm in diameter and 1.0 um long originate at Z disk, project toward the center of the two adjacent sarcomeres, thus pointing in opposite directions Composed by Primarily of F-actin A polymer of globular G-actin unit The plus end is bound to the Z disk by α actinin The minus end extends toward the center of the sarcomere 21

Thin Filament Each G-actin molecule contains an active site where the head region (S1 subfragment) of myosin binds Has the shallow grooves along the length of the F-actin double helix Occupied by pencil shape like tropomyosin molecules M asks the active sites Two chains of F-actin are wound around each other in a tight helix like two strands of pearls 22

Thin Filament Tropomyosin Polymerized to form head to tail filament that occupy the shallow grooves in the actin filaments Binding of tropomyosin masks the active sites on the actin molecules by partially overlapping them 23

Thin Filament Troponin 25-30 nm from the beginning of each tropomyosin molecule Three globular polypeptide TnT, binds the entire troponin molecule to tropomyosin TnC has a great affinity for calcium TnI binds actin, preventing the interaction between actin and myosin 24

T he structural organization of myofibrils is maintained by three proteins Titin Tight the thick filament precisely within the sarcomere A large, linear, elastic protein Extends from each half of a thick filament to the adjacent Z disk α A ctinin Hold the thin filament to the Z disk Rod-shape protein A component of the Z disk that can bind thin filament in parallel arrays Nebulin A long non elastic protein W rap ped around the entire length of each thin filament A nchoring the thin filament to the Z disk and ensuring the maintenance of the specific array 25

M uscle C ontraction and R elaxation Contraction reduces the resting length of the muscle fiber by an amount that is equal to the sum of all shortening that occur in all sarcomere of that particular muscle cell The contraction process triggered by nerve impuls, obeys the all or none law in that a single muscle fiber will either contract or not contract as a result of stimulation 26

M uscle C ontraction and R elaxation M uscle contraction Individual thick and thin filaments do not shorten The two Z disk are brought closer together as the thin filament slide past the thick filaments (Sliding filament theory) I band becomes narrower H band is extinguished Z disk move closer together The width of the A bands remains unaltered 27

M uscle C ontraction and R elaxation M uscle Contraction Sliding filament theory (Huxleys) Thin filament slide past the thick filament The sequences of action Physiology lecture 28

Actin M yosin C rossbridge 3D Animation S a n D ieg o S ta te U nivers ity C o lleg e of S c ienc es http://www.sci.sdsu.edu/movies/actin_myosin.html Based in part on Color Atlas of Physiology, Agamemnon Despopoulos, Stefan Silbernagl Thieme Medical Publishers, Inc., 1991, New York 29

M uscle C ontraction and R elaxation muscle contraction produces tension 30

M uscle C ontraction and R elaxation Relaxed muscle Thick filaments do not extend entire length of the sarcomere Thin filaments projecting from the two Z disk of sarcomere meet in the midline 31

M uscle C ontraction and R elaxation Clinical correlation Rigor mortis Occurs subsequently to death because the lack of A TP prevent the dissociation of actin and myosin Tetanus Force of contraction increases with summation of muscle twitches If action potentials continue to stimulate the muscle fiber repeatedly at short interval (high frequency) relaxation between contractions diminished until the muscle fiber achieves a state of maximal contraction Incomplete tetanus Complete tetanus 32

C lassification of skeletal muscle fiber Red muscle oxydative fibers M yoglobin (red oxygen binding pigment) >> Small diameter M any capillaries Use oxydative phosphorylation Slow twich M arathon runner 33

C lassification of skeletal muscle fiber White muscle glycolytic fibers M yoglobin (red oxygen binding pigment) << L arge diameter Small number of capillaries Fast twich Sprinter runner 34

Fiber C ontraction S peed: Fast & S low Twitch muscle fibers 35

R E D muscle fiber Glycogen? << Myoglobin? >> Capillary? >> Diameter? << Metabolism? Myosin ATPase activity? Time to develop max tension? Ca++-ATPase activity in SR? Contraction duration? Endurance? Use? 36

Glycogen? Myoglobin? Capillary? Diameter? >> << << >> Metabolism? Myosin ATPase activity? Time to develop max tension? Ca++-ATPase activity in SR? Contraction duration? Endurance? Use? Wednesday, January 13, 2010 37

I nnerva tio n o f s k eleta l m us c le Innervation of skeletal muscle by 2 nerve fiber M otor (efferent) fiber Functions in eliciting contraction Each motor neuron and muscle fibers it controls form a motor unit Sensory (afferent) fiber Pass to the muscle spindle 38

I nnerva tio n o f s k eleta l m us c le Impulse transmission at the myoneural junction M otor fiber M yelinated axon or α motor neurons Pass to the muscle terminate as motor end plate A lso known as myoneural junction A n axon terminal, synaptic cleft and muscle membrane 39

I nnerva tio n o f s k eleta l m us c le M otor fiber A xon terminal covered by Schwann cells has the mitochondria, smooth endoplasmic reticulum, synaptic vesicle Function To transmit a stimulus from nerve fiber to the skeletal muscle 40

I nnerva tio n o f s k eleta l m us c le Sequence events 41

I nnerva tio n o f s k eleta l m us c le Clinical Correlation Botulism Caused by ingestion of improperly preserved canned foods Clostridium botulinum Prevent the binding of acetyl choline to the receptor in post synaptic membrane Paralysis of the muscle 42

I nnerva tio n o f s k eleta l m us c le Clinical correlation M yasthenia gravis A n autoimune disease in which the antibodies attach to the acetyl choline receptor blocking their availability to acetylcholine Paralysis of the muscle Neurotoxins B ungaratoxin of some poisonous snakes 43

I nnerva tio n o f s k eleta l m us c le When the muscle is stretch Undergoes reflex contraction known as the Strecth reflex Preventing the tearing of muscle fibers This protection response is initiated by muscle spindle 44

I nnerva tio n o f s k eleta l m us c le M uscle spindle A n encapsulated sensory receptor located among the muscle cells Composed of Connective tissue capsule Intrafusal muscle fiber Sensory nerve fiber form 45

M uscle regeneration Satellite cells L ying beneath the basement membrane next to sarcolemma Reserve muscle precursor cells Normally quiescent A ctivated only in response to growth or muscle damage 46

R epair/regeneration of S keletal M uscle Traditional view A dult muscle cells post-mitotic Regeneration is very limited Injury repair fibrous scar formation Satellite cells have minimal contribution especially in severe muscle trauma Cardiac muscle do not have any satellite cells Lack of regeneration 47

R epair/regeneration of S keletal M uscle New perspective A ctivated of: satellite cells and other precursor cells M yonucleus M ultipotential cells (interstitial mesenchyme cells) Skeletal muscle M oderate regeneration potential Cardiac muscle have regeneration potential 48

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S mooth M uscle The repeating of light and dark cross-bands or striations is absent Involuntary L ocation: Widely distributed throughout the digestive tube Tubular portions of many organs Walls of blood vessel 51

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