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L ia D amayantiD epartment of H istology – Faculty of

M edicineUniversity of I ndonesia

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IntroductionM uscle tissue

One of the four basic tissues Properties

Contractility Converting chemical energy into mechanical work

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IntroductionThe main function of skeletal muscle

Positioning of the skeletonM ovement of the skeleton

M uscle tissue attach firmly to related boneM uscle contraction moves the skeletons

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through skeletal muscle contraction that produce muscle tension

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Development Derived from mesoderm Somatic mesoderm

Skeletal muscle Splanchnic mesoderm

Smooth muscle Splanchnopleuric mesoderm

Cardiac muscle

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Terminology in muscle Sarcolemma

M uscle cell membrane Sarcoplasm

Cytoplasm of muscle cell Sarcoplasmic reticulum

Smooth endoplasmic reticulum in the muscle cell

Sarcosomes The mitochondria of muscle cell

M uscle fiber M uscle cell

Longer than wide Living entity

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Muscle types 3 types of muscle:

Skeletal muscle Smooth muscle Cardiac muscle

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S keletal Muscle Striated muscle Regular alterantinf light

and dark cross striations M ost of voluntary

muscle mass of the body

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S keletal Muscle Organization

An 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

Delineated or surrounded by perimysium The connective tissue of

epimysium that extend inward, surrounding the muscle bundle

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S keletal Muscle 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

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Light M icroscopy Appearance M uscle fiber

A long, cylindrical and multinucleated structure

The nuclei Located in the periphery of the

muscle fiber Contact with sarcolemma

In the HE Staining Light and dark transverse cross-

bands Dark stained bands: A bands Light stained bands: I bands

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S keleta 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

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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

Lie 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

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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

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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

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Myofibril 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

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Organization of Myofibril 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

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Thick Filament Composed of two

identical heavy chain and two pairs of light chains

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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

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Thick Filament Heavy chains

Has two hinges Junction of the LM M and HM M The neck region near the two

globular heads

Each heavy chain has two light chains

Light chains Two type One of each associated with

the S1 sub-fragment

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Organization of Myofibril 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

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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

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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

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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

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The 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 Actinin 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 Wrap ped around the entire

length of each thin filament Anchoring the thin filament

to the Z disk and ensuring the maintenance of the specific array

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Muscle Contraction and Relaxation 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

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Muscle Contraction and Relaxation 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

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Muscle Contraction and RelaxationM uscle Contraction

Sliding filament theory (Huxleys) Thin filament slide past the thick filament The sequences of action → Physiology lecture

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Actin Myosin Crossbridge 3D Animation S an D ieg o S ta te U nivers ity C olleg e of S c ienc es

Based in part on Color Atlas of Physiology, Agamemnon Despopoulos, Stefan Silbernagl Thieme Medical Publishers, Inc. , 1991, New York

http://www.sci.sdsu.edu/movies/actin_myosin.html

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Muscle Contraction and Relaxation muscle contraction produces tension

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Muscle Contraction and Relaxation 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

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Muscle Contraction and Relaxation Clinical correlation

Rigor mortis Occurs subsequently to death because the lack of ATP 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

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Classification of skeletal muscle fiber

Red muscle oxydative fibers

M yoglobin (red oxygen binding pigment) >> Small diameter M any capillaries

Use oxydative phosphorylationSlow twichM arathon runner

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Classification of skeletal muscle fiber

White muscle glycolytic fibers

M yoglobin (red oxygen binding pigment) << Large diameter Small number of capillaries

Fast twichSprinter runner

?aAk,ite muscle glycol

bgvbdn vvbds sscb mjhmhtttttttttttttttkmhtttttttttmttttkmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmtthhhhhmbg bytic fibers M yoglobinbvbb sdc;[polo (red oxygen binding

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Fiber Contraction S peed: Fast & S low Twitch muscle fibers

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“RED” muscle fiber• Glycogen?• Myoglobin?• Capillary?• Diameter?

<<

>>

>>

<<

Metabolism? Myosin ATPase activity?

Time to develop max tension?Ca++-ATPase activity in SR?

Contraction duration?Endurance?

Use?

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•Glycogen?•Myoglobin?•Capillary?•Diameter?

>><<<<>>

Metabolism? Myosin ATPase activity?

Time to develop max tension?Ca++-ATPase activity in SR?

Contraction duration?Endurance?

Use?

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Innervation of s keleta l mus 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

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Innervation of s keleta l mus 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

Also known as myoneural junction

An axon terminal, synaptic cleft and muscle membrane

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Innervation of s keleta l mus c le M otor fiber

Axon 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

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Innervation of s keleta l mus c le Sequence events

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Innervation of s keleta l mus 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

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Innervation of s keleta l mus c le Clinical correlation

M yasthenia gravis An autoimune disease in which

the antibodies attach to the acetyl choline receptor blocking their availability to acetylcholine Paralysis of the muscle

Neurotoxins Bungaratoxin of some

poisonous snakes

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Innervation of s keleta l mus 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

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Innervation of s keleta l mus c le M uscle spindle

An encapsulated sensory receptor located among the muscle cells

Composed of Connective tissue capsule Intrafusal muscle fiber Sensory nerve fiber form

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Muscle regenerationSatellite cells

Lying beneath the basement membrane next to sarcolemma

Reserve muscle precursor cells Normally quiescent Activated only in response to growth or muscle

damage

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Repair/regeneration of S keletal Muscle

Traditional view Adult 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

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Repair/regeneration of S keletal Muscle

New perspective Activated 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

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S mooth Muscle The repeating of light and

dark cross-bands or striations is absent

Involuntary Location:

Widely distributed throughout the digestive tube

Tubular portions of many organs

Walls of blood vessel

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