PHYSIOLOGY OF MUSCLE PHYSIOLOGY OF MUSCLE CONTRACTIONCONTRACTION

Types of muscle tissueTypes of muscle tissue

StriatedStriated – – skeletal musclesskeletal muscles

StriatedStriated – – cardiac musclecardiac muscle

SmoothSmooth

Physiological properties of musclesPhysiological properties of muscles

ExcitabilityExcitability

ConductivityConductivity

ContractilityContractility

AutomaticityAutomaticity ( (smooth & cardiac smooth & cardiac musclesmuscles))

Physical properties of musclesPhysical properties of muscles

ElasticityElasticity ( (for striatedfor striated))

PlasticityPlasticity ( (for smoothfor smooth))

Skeletal muscles functionsSkeletal muscles functions

1.1. Maintain body postureMaintain body posture 2.2. Body movement in spaceBody movement in space3.3. Body parts movement with regards to Body parts movement with regards to

each othereach other4.4. Enable thermogenesisEnable thermogenesis

SarcomereSarcomere is a structural & is a structural & functional unit of skeletal functional unit of skeletal

musclemuscleIs a part of muscle fiber between 2 Z-linesIs a part of muscle fiber between 2 Z-linesContains transverse tubuliContains transverse tubuli ( (sarcoplasmic sarcoplasmic reticulumreticulum), ), myozin & actin fibers located in myozin & actin fibers located in orderorder

Relaxed sarcomere

Sarcomere in the state of contraction

Contractile elementsContractile elements

ААctinctin –– –– a double helical filament with a double helical filament with tropomyosintropomyosin && troponin troponin attachedattachedММyosinyosin – – asymmetric hexamer with a asymmetric hexamer with a molecular mass 460 kDa. Myosin has a molecular mass 460 kDa. Myosin has a fibrous tail made of 2 intertwined helices.fibrous tail made of 2 intertwined helices.Each helix has a globularEach helix has a globular head portion, head portion, which possesseswhich possesses АТАТPP-а-аsese activityactivity, а , а flexible segmentflexible segment connects head to the tailconnects head to the tail

Motor unit structureMotor unit structure

MOTOR UNITMOTOR UNIT

Consists of motor neuron & a group of Consists of motor neuron & a group of muscle fibers, which are supplied bymuscle fibers, which are supplied by axon axon of this motor neuronof this motor neuronThe number of muscle fibers in one motor The number of muscle fibers in one motor unit depends on the functionunit depends on the function, , which is which is performed by this muscleperformed by this muscle (( from from 10 10 ttо о 30 00030 000 fibers fibers))

ADEQUATE STIMULIADEQUATE STIMULI

Nervous impulseNervous impulse is the only adequate is the only adequate stimulus for skeletal muscle contractionstimulus for skeletal muscle contraction

NEURO-MUSCULAR SYNAPSENEURO-MUSCULAR SYNAPSE

Contact between motor neuron axon & Contact between motor neuron axon & muscle fiber membranemuscle fiber membrane::Axon ending (pre-synaptic membrane)Axon ending (pre-synaptic membrane)Motor endplate (postsynaptic Motor endplate (postsynaptic membrane)membrane)Synaptic cleftSynaptic cleft

AP

AP

AP

EPP

EPP EPP

EPP

Ach

Аch

AP

Са++

Са++

АchАch-receptorAP

Na+

Na+EPP

Cholinesterase

Na+

Na+

Chemical gated channels

Electrical gated channel

STAGESTAGESS OF SYNAPTIC OF SYNAPTIC TRANSMISSIONTRANSMISSION

1. Axon stimulation and excitation of presynaptic membrane.

2. Ca 2+ entry

3. Synaptic vesicles reach presy- naptic membrane and rupture

4. Synaptic transmitter (Ach) is released

5. Combination of Ach and the receptor

6. Excitation of postsynaptic membrane

Mechanism of neuro-muscular Mechanism of neuro-muscular synapse worksynapse work

1.1. Discharge of motor neuron & AP Discharge of motor neuron & AP spreading to axon endingspreading to axon ending

2.2. Opening of calcium voltage gated Opening of calcium voltage gated channelschannels

3.3. Calcium entryCalcium entry4.4. Acetylcholine release at motor endplateAcetylcholine release at motor endplate5.5. Binding of acetylcholine to nicotinic Binding of acetylcholine to nicotinic

acetylcholine receptorsacetylcholine receptors

5.5. Opening of sodium chemically gated Opening of sodium chemically gated channels at endplatechannels at endplate

6.6. Increased sodium conductance in Increased sodium conductance in endplate membraneendplate membrane

7.7. Generation of endplate potential (EPP)Generation of endplate potential (EPP)8.8. Generation of action potential in muscle Generation of action potential in muscle

fibers (due to opening of voltage gated fibers (due to opening of voltage gated sodium channels)sodium channels)

Cross-bridgesCross-bridges

Electro-chemical interactionElectro-chemical interaction

Inward spread of depolarization along T Inward spread of depolarization along T tubulestubulesCharge movement of the slow calcium Charge movement of the slow calcium voltage channel (dihydropyridine receptor) of voltage channel (dihydropyridine receptor) of the transverse tubular membrane the transverse tubular membrane Opening of calcium release channel Opening of calcium release channel (ryanodine receptor) in sarcoplasmic (ryanodine receptor) in sarcoplasmic reticulumreticulumCalcium concentration in sarcoplasm Calcium concentration in sarcoplasm increases 100 timesincreases 100 times

Са++ Са++Са++

SPR

triade

myosin

actinΖ Ζ

dehydropyridin ryanodin

Without AP calcium influx Without AP calcium influx into cytoplasm is impossibleinto cytoplasm is impossible!!!!

Electro-mechanical couplingElectro-mechanical coupling

Calcium binds troponinCalcium binds troponinTropomyosin uncovers myosin binding Tropomyosin uncovers myosin binding sites of actinsites of actinMyosin heads get bound to these active Myosin heads get bound to these active sitessites to form cross-bridgesto form cross-bridges

The sliding filament cross-bridge The sliding filament cross-bridge model model

Thin actin filaments slideThin actin filaments slide along thick along thick myosin ones due to cross-bridges myosin ones due to cross-bridges formationformation

As a result sarcomere & muscle fiber As a result sarcomere & muscle fiber length decreaseslength decreases

Chemo-mechanical interactionChemo-mechanical interaction

Myosin heads bend, allowing actin filaments Myosin heads bend, allowing actin filaments to slide along myosin onesto slide along myosin onesSliding goes smoothly because myosin heads Sliding goes smoothly because myosin heads get attached to the subsequent active centers get attached to the subsequent active centers of actinof actin..The higher is cytoplasm calcium The higher is cytoplasm calcium concentrationconcentration, , the more bridges can be the more bridges can be formed and the stronger is contractionformed and the stronger is contraction

Mechanism of muscle relaxationMechanism of muscle relaxation

Calcium is pumped back into sarcoplasmic Calcium is pumped back into sarcoplasmic reticulumreticulum

Calcium is released from troponinCalcium is released from troponin

Cessation of interaction between actin & Cessation of interaction between actin & myosinmyosin

Energy expenditure during muscle Energy expenditure during muscle contractioncontraction

Na/K pump workNa/K pump workSliding of myosin heads along actin filamentsSliding of myosin heads along actin filamentsCalcium pump workCalcium pump workMost energy is spent for relaxationMost energy is spent for relaxation

Distribution of neuro-muscular Distribution of neuro-muscular synapses in sceletal musclessynapses in sceletal muscles

««All or noneAll or none»» law law

Single muscle fiber obeys this lawSingle muscle fiber obeys this law::Subthreshold irritation doesn’t causeSubthreshold irritation doesn’t cause

contractioncontraction, а, аnd threshold irritation causesnd threshold irritation causes maximal contractionmaximal contraction, , i.ei.e. . the amplitude of the amplitude of muscle contraction doesn’t depend upon muscle contraction doesn’t depend upon the force of irritationthe force of irritation

««All or noneAll or none»» law law

The whole muscle doesn’t obey this law The whole muscle doesn’t obey this law because it consists of many motor units because it consists of many motor units which all have different thresholds of which all have different thresholds of depolarizationdepolarization

Types of contractionTypes of contraction

IsometricIsometric – – tension increase without length tension increase without length increaseincreaseIsotonicIsotonic – – length decrease at the same length decrease at the same tensiontensionMixedMixed - - auxotonicauxotonic

Types of muscle contractionTypes of muscle contraction

TwitchTwitchТеТеtanustanusТоТоnusnus

Types of muscle irritation in Types of muscle irritation in experimentexperiment

Indirect irritationIndirect irritation – – impulse is applied to the impulse is applied to the nervous ending of motor neuronnervous ending of motor neuronDirect irritationDirect irritation– – impulse is applied to the impulse is applied to the muscle directlymuscle directly

Single muscle contraction (twitch)Single muscle contraction (twitch)

CONTRACTIONPHASE

RELAXATION PHASE

LATENT PERIOD

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TETANUSTETANUS

Strong & long lasting contraction in Strong & long lasting contraction in response to series of irritationsresponse to series of irritations..Develops due to summation of single Develops due to summation of single muscle contractionsmuscle contractions as the result of as the result of calcium concentration increasecalcium concentration increase

Summation of single contractionsSummation of single contractions

SUMMATION

TIME, 0,01 SEC

SINGLE CONTRACTIONS

““Toothed” tetanusToothed” tetanus

Develops when each subsequent Develops when each subsequent stimulus gets into the period of muscle stimulus gets into the period of muscle relaxationrelaxation so that so that interval between two impulses is less than interval between two impulses is less than the duration of single muscle contractionthe duration of single muscle contraction, , but longer than contraction phasebut longer than contraction phase

TOOTHED TETANUS

Smooth tetanusSmooth tetanus

Each subsequent stimulus is getting Each subsequent stimulus is getting into contraction phase, i.e.into contraction phase, i.e. interval interval between two subsequent stimuli is between two subsequent stimuli is shorter shorter than contraction phase durationthan contraction phase duration, , but but longer than refractory periodlonger than refractory period . .

SMOOTH TETANUS

OPTIMUMOPTIMUM

Is frequency of irritation at which tetanus Is frequency of irritation at which tetanus reaches its maximum amplitudereaches its maximum amplitudeEach subsequent stimulus gets into the Each subsequent stimulus gets into the supernormal period, i.e. right after AP is oversupernormal period, i.e. right after AP is overThis leads to constant high concentration of This leads to constant high concentration of calcium in cytoplasm (calcium pump has no calcium in cytoplasm (calcium pump has no time to switch on)time to switch on)

PESSIMUMPESSIMUM

Is frequency of irritation at which there is no Is frequency of irritation at which there is no summation of contractionssummation of contractionsEach subsequent stimulus gets into the Each subsequent stimulus gets into the refractory period (during the AP refractory period (during the AP development)development)All the sodium channels stay inactivated & All the sodium channels stay inactivated & new AP development is impossiblenew AP development is impossible

OPTIMUM PESSIMUM OPTIMUMSMOOTH

TETANUS

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Muscle fibers classificationMuscle fibers classification

Each muscle fiber has just Each muscle fiber has just one synapseone synapse

SlowSlow phasic fibers of oxydative phasic fibers of oxydative typetype

rich in myoglobin & mitohondriarich in myoglobin & mitohondria Red in colourRed in colour Fatigue develops slowlyFatigue develops slowlyVery many fibers in one motor unitVery many fibers in one motor unit ( (up toup to 30 000)30 000)Compose muscles which maintain postureCompose muscles which maintain posture

FastFast phasic fibers of phasic fibers of oxydativeoxydative typetype

Rich in mitohondriaRich in mitohondriaAble to synthesiseAble to synthesise АТ АТPP due to oxydative due to oxydative phosphorylationphosphorylationPerform fast contractionsPerform fast contractionsDevelop fatigue slowlyDevelop fatigue slowlyFewer fibers in one motor unit than in slow Fewer fibers in one motor unit than in slow onesones

FastFast phasicphasic withwith glucolitic glucolitic typetype of of oxydationoxydation

Few mitohondriaFew mitohondriaАТАТPP is formed due to glucolisisis formed due to glucolisisNo myoglobinNo myoglobin ( (white in colourwhite in colour))Quickly contract & develop fatigue quicklyQuickly contract & develop fatigue quicklyLittle number of fibers in one motor unitLittle number of fibers in one motor unit

Tonic fibersTonic fibers

Motor neuron axon forms many synapsesMotor neuron axon forms many synapsesSlowly contract & slowly relaxSlowly contract & slowly relaxLowLow АТ АТPP--asease activity of myosinactivity of myosinForm external muscles of the eyeForm external muscles of the eye

Muscle strengthMuscle strength

Depends on muscle thickness & Depends on muscle thickness & physiological cross sectionphysiological cross section

Muscle workMuscle work

Is energy spent on body movement with a Is energy spent on body movement with a certain force to a certain distansecertain force to a certain distanse::

A = F x SA = F x SIfIf FF=0, =0, thenthen А=0 А=0IfIf SS=0, =0, thenthen А=0 А=0

Maximum work is performed at middle Maximum work is performed at middle loadsloads

Amax=Amax= Fmed x SmaxFmed x Smax

FATIGUEFATIGUE

A process of temporal decrease of muscle A process of temporal decrease of muscle workabilityworkability..Develops due to the decrease of ATP in Develops due to the decrease of ATP in muscle fibermuscle fiber or mediator in neuro-or mediator in neuro-muscular synapsemuscular synapseIn neuro-muscular preparation fatigue In neuro-muscular preparation fatigue develops first of all in the synapsedevelops first of all in the synapse!!

nervemuscle

stimulator stimulator

Muscle at fatigueMuscle at fatigue

Non-fatigued muscle

Orbelli- Genetzynsky phenomenonOrbelli- Genetzynsky phenomenon

Myograme myogramme

FATIGUE IN THE BODYFATIGUE IN THE BODY

Fatigue first develops in the nervous centersFatigue first develops in the nervous centers – – it’s a defense mechanismit’s a defense mechanismMuscles still have reserve of energyMuscles still have reserve of energyproofproof – – Sechenov’s experiments with active Sechenov’s experiments with active restrest

ErgographyErgography

A method of muscle work registrationA method of muscle work registrationErgogramme curve can show signs of Ergogramme curve can show signs of fatiguefatigue::

Decreased magnitude of contractionDecreased magnitude of contractionProlonged phase of relaxationProlonged phase of relaxationDecreased frequency of contractionDecreased frequency of contraction

SMOOTH MUSCLESSMOOTH MUSCLES

Single unit (visceral) smooth Single unit (visceral) smooth musclesmuscles

All internal organsAll internal organsLots of necsusesLots of necsuses ((coloured redcoloured red))Few nervous endingsFew nervous endings ((coloured greencoloured green))

Multiunit smooth musclesMultiunit smooth muscles

Ciliary muscle & Ciliary muscle & musculus dilator pupilimusculus dilator pupiliHave high density of Have high density of neuro-muscular neuro-muscular synapses (coloured synapses (coloured greengreen))

Smooth muscles nervous supplySmooth muscles nervous supply

Muscle cells with nervoussupply

Muscle cells without nervoussupply

Peculiarities of smooth musclesPeculiarities of smooth muscles

Spindle like cells lie close to each otherSpindle like cells lie close to each otherTight contacts between the cellsTight contacts between the cells – – necsusesnecsusesActin & myosin don’t have regular locationActin & myosin don’t have regular locationSarcoplasmic reticulum is developed less Sarcoplasmic reticulum is developed less than in skeletal musclesthan in skeletal muscles

Nervous supply of smooth muscles Nervous supply of smooth muscles Supplied by sympathetic & Supplied by sympathetic & parasympathetic nervesparasympathetic nervesNo synapses, nervous endings form No synapses, nervous endings form varicosesvaricosesMediator is released into the intracellular Mediator is released into the intracellular fluidfluidAfter one cell is excited AP spreads to After one cell is excited AP spreads to other cells along necsusesother cells along necsuses ( (electrical electrical synapsessynapses))The whole muscle contracts The whole muscle contracts simultaneouslysimultaneously ( (functional syncytiumfunctional syncytium))

Adequate stimuliAdequate stimuli

Nervous impulseNervous impulseMechanical stretchingMechanical stretchingChemical substances (hormones)Chemical substances (hormones)

Peculiarities of excitabilityPeculiarities of excitabilityThreshold of depolarization is lower than Threshold of depolarization is lower than in striated musclesin striated musclesMembrane is more permeable for sodium, Membrane is more permeable for sodium, that is why MP is lowerthat is why MP is lower (-50, -60 (-50, -60 mVmV))AP amplitude is lower and its duration is AP amplitude is lower and its duration is longerlongerDepolarization opens up voltage-gated Depolarization opens up voltage-gated calcium channelscalcium channels, , calcium influx slows calcium influx slows down repolarizationdown repolarization

AUTOMATICITYAUTOMATICITY

The ability of cell to generate AP without The ability of cell to generate AP without any external stimuliany external stimuliSmooth muscle cell at the state of rest is Smooth muscle cell at the state of rest is permeable to sodiumpermeable to sodium, , which slowly which slowly depolarizes the cell to the critical level & depolarizes the cell to the critical level & AP developsAP develops

Electrochemical coupling in smooth Electrochemical coupling in smooth musclesmuscles

AP opens up calcium channels,AP opens up calcium channels, calcium calcium enters the cellenters the cell..Ligands activate phospholipaze Ligands activate phospholipaze С С on the on the cell membrane, activation of inositol-3P & cell membrane, activation of inositol-3P & diacylgliceroldiacylglicerol..inositol-3P releases calcium from EPS, inositol-3P releases calcium from EPS, which starts contractionwhich starts contraction

Mechanism of calcium level Mechanism of calcium level regulation in smooth musclesregulation in smooth muscles

in EPS

channel

pumpinositol-3P

receptorligand

Peculiarities of smooth muscles Peculiarities of smooth muscles contractioncontraction

In cytoplasm calcium binds with calmoduline In cytoplasm calcium binds with calmoduline & activates proteinkinase& activates proteinkinase . . ProteinkinaseProteinkinase phosphorilates myosin headphosphorilates myosin head. . Actin-myosin cross-bridges are formedActin-myosin cross-bridges are formedDrop of calcium concentration in myoplasmDrop of calcium concentration in myoplasm causes dephosphorilation of myosin head & causes dephosphorilation of myosin head & cross-bridges are destroyedcross-bridges are destroyed Muscle relaxesMuscle relaxes