ByDr.H.Gusbakti,MD, MSC,PKK,AIFM

Professor of PhysiologyUniversity Islamic Of North Sumatera

MUSCLE TISSUE

Muscles in human bodySpecialised excitable tissues~ 50 % body weightAbility to contractContractions provide movements Do work

Move body or limbsPush, pull or hold an external load or objectMix or move food through the gastrointestinal trackPump blood out of the heart to the blood vesselsContract uterus for birth of foetusMicturition and defaecation

MUSCLE OF TYPE

Three types of muscle:1.Skeletal muscle2.Cardiac muscle3.Smooth muscle

Skeletal Muscle

Long cylindrical cells

Many nuclei per cell

Striated Voluntary Rapid

contractions

Cardiac Muscle

Branching cells One or two nuclei per cell Striated Involuntary Medium speed contractions

Smooth Muscle

Fusiform cells One nucleus per cell Nonstriated Involuntary Slow, wave-like contractions

Basic Characteristics of Muscle Tissues

ExcitabilityResponse to stimuli

ConductivityAble to conduct action potential

ContractibilityAble to shorten in length

ExtensibilityStretches when pulled

ElasticityTends to return to original shape & length after contraction or extension

Skeletal Muscle

Attached to bones & moves skeleton Makes up 40% of BW in men and 32% of BW in women

Main functions of skeletal muscle:Initiate movementsPerform workMaintain postureStabilise jointsGenerate heat

Level of Organisationin Skeletal Muscle

Skeletal Muscle(organ)

Fascicle(bundle of muscle fibres)

Muscle Fibre(cell)

Myofibril

Sarcomere

Filaments(Thin –actin) (Thick -myosin)

Membranes of Skeletal Muscle

Muscle surrounded by epimysiumBundles of fibres(fascicles) surrounded by perimysiumMuscle fibresurrounded by endomysiumThese connective tissues extend beyond the ends of

muscle to form tendons that attach muscle to bones

Skeletal Muscle Fibre

Large, elongated, shape like cylinder

10 –100 μm in diameter, up to 750,000 μm (0.75 m) in length (extend entire length of muscle)

Multinucleated with abundant of mitochondria

Sarcolemma(cell membrane)Sarcoplasm(muscle cell

cytoplasm)Sarcoplasmic reticulum

(modified ER)

Transverse tubules (T-tubules) –internal conduction system

Myofibrils for contractionSarcomeres–regular arrangement

of thin (actin) & thick (myosin) filaments

Actinfilaments interdigitatewith myosin filaments

Appears striated under microscope

Structure of a Skeletal Muscle Fibre

Electron Micrograph of Skeletal Muscle

SarcomereThe functional unit of skeletal muscleMulti-protein complexes composed different filament systems:

Thin filament systemThick filament system

Muscle Tissue

• Skeletal Muscle• Cardiac Muscle• Smooth Muscle

Microanatomy of Skeletal Muscle

Z line Z line

H Band

Sarcomere Relaxed

Sarcomere Partially Contracted

Sarcomere Completely Contracted

Binding Site Tropomyosin

Troponin

Myosin

Sarcomere sarcomere

Sarcomere

Sarcomere

Sarcomere

A band (dark band) consists of a stacked set of thick filaments

I band (light band)Consists of the array of thin filaments, and is the region where they do not overlap the thick filaments

H zoneThe lighter area in the centre of A band where the thin filaments do not overlap with thick filaments

M lineConsists of supporting proteins that hold the thick filaments together vertically within each stack

Z lineConsists of supporting proteins that hold the thin filaments together vertically within each stack

Area between two Z lines is called a sarcomere

Sarcomere

Thin Filament

Actin Spherical in shape, with a special binding site for attachment with myosin cross bridge Joined into two strands and twisted together to form the backbone of a thin filament

TropomyosinThreadlike proteins that lie end-to-end alongside the groove of the actin spiralCovers active sites of actin

Troponin complex binds to actin & holds tropomyosin in place

Thin Filament

Thin FilamentTroponinComplex

TnT –binds to tropomyosinTnC –binds to Ca2+TnI –binds to actin

Thick Filament

Each thick filament is composed of several hundred myosin molecules packed togetherA single myosin protein looks like 2 golf clubs with shafts twisted about one anotherMyosin molecules have elongated tails & globular headsHeads form cross-bridges between thick and thin filaments during contraction

Thick FilamentCross Bridges

Each cross bridge has two important sites:An actin-binding siteA myosin ATPase site

Organisationof Actinand MyosinCross bridges

Thin filaments are arranged hexagonally around thick filamentsEach thin filament is surrounded by 3 thick filamentsCross bridges project from each thick filament in all 6 directions toward the surrounding thin filaments

Contraction of Muscle FibresDone by sliding actin filaments

Contraction of Muscle Fibres

Contraction of Muscle Fibres

Sliding Filament TheoryContraction occurs by actin filaments sliding into myosin filamentsActin filaments move, myosin filaments remain stationarySarcomeres shortenedCause whole muscle to contract

Contraction of Muscle FibresRole of Calcium

Ca2+released from sarcoplasmic reticulumCa2+binds to troponin CTroponin turns, moves tropomyosin & exposes actin active site

Contraction of Muscle FibresRole of Calcium

Myosin head binds to actin active site, form cross-bridge, move & produces powerful strokesActin slides in –muscle fibre contractsCross-bridge action continues while Ca2+is presentWhen action potential stops, Ca2+is pumped back to SRTropomyosin covers back actin’s active siteRelaxation occurs

Contraction of Muscle FibresRole of Calcium

Contraction of Muscle FibresRole of ATP

ATP split by myosin ATPase ; ADP and Pi remain attached to myosin; energy is stored within the cross bridgeMg2+must be attached to ATP before ATPase can split the ATPCa2+ released on excitation, removes inhibitory influence from actin → energised myosin cross bridge bind with actinCross bridge bends and causes power strokeADP and Piare released after power stroke is completedATPase site is free for attachment of another ATPAttachment of new ATP permits detachment of cross bridge

Contraction of Muscle Fibres

Contraction of Muscle Fibres

All the cross bridges’ power strokes are directed toward the centre of the sarcomereAll 6 of the surrounding thin filaments on each end of the sarcomere are pulled inward simultaneously

Contraction of Muscle FibresRigor Mortis

“Stiffness of death” –a generalised locking in place of skeletal muscle that begins 3 to 4 hours after deathFollowing death, [Ca2+]ibegins to riseThis Ca2+moves the regulatory proteins aside, permitting actin bind with the myosin cross bridges, which were already charged with ATP before deathNo fresh ATP available after death, actin and myosin remain bound in rigor complexResulting in stiffness condition of dead muscles

Electrical Properties of Muscle Fibres

Resting membrane potential:-90mV

When an adequate stimulus is given → action potential

potential: +30mV

Depolarisation is due to influx of Na+Time taken: 1 –2 msecAbsolute refractory period & relative refractory period present

Action potential results in muscle contraction

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Action Potential and Muscle TwitchT

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Latent periodThe delay between stimulation and the onset of contraction (a few msec)

Contraction timeThe time from the onset of contraction until peak tension is developed (average ~ 50 msec)

Relaxation timeThe time from peak tension until relaxation (~ 50 msec or more)

A single contraction/relaxation cycle is called a muscle twitch

Excitation-Contraction CouplingRefers to the series of events linking muscle excitation (electrical events) to muscle contraction (mechanical events)

Electrical events –presence of action potentialMechanical events –cross-bridge activity

Electrical events come first before mechanical eventsCa2+ is the link between excitation and contraction

Excitation-Contraction Coupling

The surface membrane at each junction of A band and I band dips into muscle fiber to form a T tubuleAction potential on the surface membrane spreads down into the T tubuleThe presence of local action potential in T tubule induces permeability changes in the sarcoplasmic reticulum

Sarcoplasmic Reticulum (SR)

Excitation-Contraction CouplingRelease of Ca2+ from SR

When action potential is propagated down the T tubules, local depolarisation activates the voltage-gated dihydropyridine receptors in T tubule These activated receptors in turn trigger the opening of Ca2+-release channels (alias ryanodine receptors) in adjacent lateral sacs of SRCa2+ is released into the surrounding sarcoplasm

Relaxation of Muscle FibresWhen ACh is removed from the neuromuscular junction, the muscle fibre action potential ceasesNo longer a local potential in T tubules to trigger Ca2+ releaseReleased Ca2+ is pumped back into the lateral sacs by Ca2+-ATPase pumpRemoval of sarcoplasmic Ca2+allows the troponin-tropomyosin complex to slip back into its blocking positionActin and myosin are no longer able to bind at the cross bridgesThin filaments are able to return passively to their resting positionRelaxation occurs

Excitation-Contraction Coupling

Excitation-Contraction Coupling and RelaxationSummary of Events

1.Ach released from the terminal of a motor neuron initiates an action potential in the muscle fibres2.Muscle action potential travels down T tubule3.Causes SR to release Ca2+ into sarcoplasm4.Ca2+ binds to troponin, exposing actin’s cross-bridge binding sites5.Myosin head binds to active site, form cross-bride, moves and produces power stroke

6.Actin slides in, muscle fibre contracts resulting in contraction of whole muscle7.ADP and Piare released after the power stroke is complete8.New ATP binds to myosin head; detachment of the cross bridge9.Cross-bridge action continues while Ca2+ is present10.When action potential stops, Ca2+ pumped back to SR11.Tropomyosin covers back active sites12.Relaxation occurs

Neuromuscular Junction

Acetylcholine Opens Na+ Channel

Muscle Contraction Summary• Nerve impulse reaches myoneural junction• Acetylcholine is released from motor neuron• Ach binds with receptors in the muscle

membrane to allow sodium to enter• Sodium influx will generate an action potential

in the sarcolemma

Muscle Contraction Continued

• Action potential travels down T tubule• Sarcoplamic reticulum releases calcium• Calcium binds with troponin to move the

troponin, tropomyosin complex• Binding sites in the actin filament are

exposed

Muscle Contraction Continued

• Myosin head attach to binding sites and create a power stroke

• ATP detaches myosin heads and energizes them for another contaction

• When action potentials cease the muscle stop contracting

Motor UnitAll the muscle cells controlled by one

nerve cell

Motor Unit Ratios

• Back muscles– 1:100

• Finger muscles– 1:10

• Eye muscles– 1:1

ATP

Creatine

• Molecule capable of storing ATP energy

Creatine + ATP Creatine phosphate + ADP

Creatine Phosphate

• Molecule with stored ATP energy

Creatine + ATPCreatine phosphate + ADP

Muscle Fatique

• Lack of oxygen causes ATP deficit• Lactic acid builds up from anaerobic

respiration

Muscle Atrophy

• Weakening and shrinking of a muscle• May be caused

– Immobilization– Loss of neural stimulation

Muscle Hypertrophy

• Enlargement of a muscle

• More capillaries• More mitochondria• Caused by

– Strenuous exercise– Steroid hormones

Steroid Hormones

• Stimulate muscle growth and hypertrophy

Muscle Tonus

• Tightness of a muscle• Some fibers always contracted

Tetany

• Sustained contraction of a muscle• Result of a rapid succession of nerve impulses

Tetanus

Refractory Period

• Brief period of time in which muscle cells will not respond to a stimulus

Refractory

Skeletal Muscle Cardiac Muscle

Refractory Periods

Isometric Contraction

• Produces no movement• Used in

– Standing– Sitting– Posture

Isotonic Contraction

• Produces movement• Used in

– Walking– Moving any part of the body