PhysiologyPhysiology

Skeletal Muscle Contraction

Connective TissueConnective TissueEndomysium

◦ Surrounds each muscle fiber (cell)◦ Attaches to Z-lines in each sarcomere

Perimysium◦ Surrounds bundles (fascicles) of muscle fibers◦ Attaches to endomysium

Epimysium◦ Attaches to the Perimysium◦ Continuous with tendon

SarcomereSarcomereRepeating Patterns within the

myofibrilsMyofibrils

◦Proteins within the myofibers◦Myosin◦Actin

Muscle AnatomyMuscle AnatomySarcolemma

◦Muscle fiber cell membraneMyofibrils

◦Highly organized bundles of contractile and elastic proteins

◦Carries out the work of contraction

Myofibrils = Contractile Organelles of Myofiber

Actin Myosin

Tropomyosin Troponin

Titin Nebulin

ContractileContractile

RegulatoryRegulatory

AccessoryAccessory

Contain 6 types of protein:

Titin and Nebulin

Titin: biggest protein known (25,000 aa); elastic! Stabilizes position of contractile filaments Return to relaxed location

Nebulin: inelastic giant protein Alignment of A & M

Changes in a Sarcomere during Contraction

MyosinMyosinMyo- muscleMotor protein of the myofibrilThick filamentAttaches to the M-line

◦Heads point towards Z-linesMyosin heads are clustered at

the ends of the filamentMyosin tails are bundled together

Role of calcium

Troponin complex

Tropomyosin

•Troponin and Tropomyosin bind to actinblock the actin – myosin binding sites

•Troponin is a calcium binding protein

ActinActinThin Filament

◦ Attached to Z-linesGlobular protein

◦ G-Actin◦ Has binding site for myosin head◦ Forms a Cross-Bridge when myosin binds to G-

actin◦ Five Actin proteins surround the myosin in 3-D

pattern

ActinActinTropomyosin

◦Protein that covers over the myosin binding site on G-Actin Myosin head can’t bind to G-Actin,

muscle relaxes

◦If the binding site on G-Actin is uncovered by removing Tropomyosin then myosin and actin bind, muscle contracts

ActinActinTroponin C

◦ Protein attached to Tropomyosin◦ When Troponin C changes shape it pulls on

Tropomyosin Calcium binding to Troponin C causes this

protein to change shape ◦ Tropomyosin moves and uncovers the binding

site on G-Actin, so Actin and Myosin can bind Contraction

Regulation of Contraction by Troponin and Tropomyosin

Tropomyosin blocks myosin binding site (weak binding possible but no powerstroke)

Troponin controls position of tropomyosin and has Ca2+ binding site

Ca2+ present: binding of A & M

Ca2+ absent: relaxation

Muscle AnatomyMuscle AnatomySarcoplasmic Reticulum

◦ Modified endoplasmic reticulum◦ Wraps around each myofibril like a piece of

lace◦ Stores Calcium

Terminal Cisternae◦ Longitudinal tubules

Transverse tubules (T-tubules)◦ Triad-two flanking terminal cisternae and one

t-tubule◦ T-tubules are continuous with cell membrane

When Troponin binds calcium it moves Tropomyosin away from the actin-myosin binding site

CaCa

Where does Calcium come from?

Intracellular storage called Sarcoplasmic Reticulum Surround each myofibril of the whole muscle Contains high concentration of calcium

Transverse Tubules connects plasma membrane to deep inside muscle

T-TubulesT-TubulesRapidly moves action potentials

that originate at the neuromuscular junction on the cell surface

Motor nerve

Neurotransmitter receptors

Membrane depolarization or APs carried deep into the muscle by T-tubules

+

T-tubule

SR

MyT-tubule

SR

SR

Ryanodine Receptor

Dihydropyridine receptor

myoplasm

T-tubule(extracellular)

SR

Myoplasm(intracellular)

++

++++

_ _ _ _ _ _

Ca++Ca++Ca++

_ _ _

+++

_ _ _+++

Ca++ pump

Myosin filament

Myosin head group

S2 link

Actin filament Binding sites

Stretching of the link generates tension

Weakbinding

Strongbinding

Equal and opposite forceon thick filament

Why do thin filaments move?

Net forceNet force

Sliding Filament TheorySliding Filament TheoryWhen myosin binds to the

binding site on G-actin muscular contraction occurs.

The more myosin that bind to G-actin the greater the force of contraction

Calcium must be present

Sliding Filament TheorySliding Filament Theory Cross Bridge

◦ Myosin in the High Energy Configuration binds to G-Actin

◦ ADP + Pi are bonded to the myosin head when the cross bridge forms

Power Stroke◦ When the myosin and actin bind the myosin head

changes shape◦ Myosin pulls the actin and pulls on the Z-line◦ Sarcomere shortens◦ ADP+Pi no longer binds to myosin head

Sliding Filament TheorySliding Filament TheoryATP binds to the myosin head

◦Myosin changes to its Low Energy Confirmation

◦In the Low Energy Confirmation Myosin breaks its bonds with Actin Rigor Mortis

Lack of ATP Build up of Lactic Acid

Sliding Filament TheorySliding Filament TheoryATPase

◦ATP is hydrolyzed to ADP + Pi◦ATPase is on the myosin head◦Myosin changes shape back to its

High Energy Confirmation

Sliding Filament TheorySliding Filament TheorySome Myosin heads detach from

Actin while other heads continue to keep their attachments◦No slipping of the Z-lines◦Contraction is held in place

Rigor mortis

Actin + myosin Actomyosin complex

What if we don’t have this?

XATP

Events at Neuromuscular Events at Neuromuscular JunctionJunctionConverts a chemical signal from

a somatic motor neuron into an electrical signal in the muscle fiber

Events at Neuromuscular Events at Neuromuscular JunctionJunctionAcetylcholine (Ach) is released from the

somatic motor neuronAch initiates an action potential in the

muscle fiberThe muscle action potential triggers

calcium release from the sarcoplasmic reticulum

Calcium combines with troponin C and initiates contractions

Events at Neuromuscular Events at Neuromuscular JunctionJunctionAch binds to cholinergic

receptors on the motor end plateNa+ channels open

◦Na+ influx exceeds K+ efflux across the membrane

End-Plate Potential (EPP)◦EPP reaches threshold and initiates a

muscle action potential

Events at Neuromuscular Events at Neuromuscular JunctionJunctionAction Potentials move down the

membrane◦K+ builds up in the t-tubules◦Depolarization occurs

Calcium gates on the SR opens Calcium diffuses into the cytoplasm of

the cell

Excitation-Contraction CouplingExcitation-Contraction Coupling

The process where muscle action potentials initiate calcium signals that in turn activates a contraction-relaxation cycle

Initiation of Contraction

Excitation-Contraction Coupling explains how you get from AP in axon to contraction in sarcomere

ACh released from somatic motor neuron at the Motor End Plate

AP in sarcolemma and T-Tubules

Ca2+ release from sarcoplasmic reticulum

Ca2+ binds to troponin

Nicotinic cholinergic receptors on motor end plate = Na+ /K+ channels

Net Na+ entry creates EPSP

AP to T-tubules

DHP (dihydropyridine) receptors in T-tubules sense depolarization

Details of E/C Coupling

Nicotinic Cholinergic Receptors

DHP (dihydropyridine) receptors open Ca2+ channels in t-tubules

Intracytosolic [Ca2+]

Contraction

Ca2+ re-uptake into SR

Relaxation

Excitation-Contraction CouplingExcitation-Contraction Coupling

High cytosolic Calcium levels binds to Troponin C◦ Tropomyosin moves to the “on” position and

contraction occursCalcium-ATPase pumps Calcium back

into the SR The more myosin heads that binds to

actin to stronger the force of contraction

1. Synaptic Depolarization of the plasma membrane is carried into the muscle by T-Tubules

2. Conformational change of dihydropyridine receptor directly opens the ryanodine receptor calcium channel

3. Calcium flows into myoplasm where it binds troponin

4. Calcium pumped back into SR

Summary of events

Neuromuscular JunctionNeuromuscular JunctionThe more terminal boutons to

attach to myofibers the greater the control of the muscle.

Recruitment◦The greater the number of terminal

boutons attached to myofibers there is more fine control of the muscle

Excitation-Contraction CouplingExcitation-Contraction Coupling

Twitch◦A single contraction-relaxation cycle

in a skeletal muscle fiber◦A single action potential in a muscle

fiberLatent Period

◦Between the muscle action potential ◦Time required for excitation-

contraction coupling to take place

Is There Truth In Advertising?Is There Truth In Advertising?

Is the banana company telling the truth when they claim that bananas being high in Potassium actually prevents or relieves muscle cramps?

If so, how does this increase in Potassium relieve muscle cramps?

If not, why not and how do we actually relieve muscle cramps?

Muscle Contraction and ATP Muscle Contraction and ATP SupplySupplyPhosphocreatine

◦Backup energy source◦Quick energy used up in approx. 15

minutes

Causes of FatigueCauses of FatigueCentral Fatigue

◦Subjective feelings of tiredness◦Arises in the CNS◦Psychological fatigue precedes

physiological fatigue in the muscles Subjective feelings of tiredness Low pH may cause fatigue

Muscle Fiber Classification

Oxidative only

Oxidative or glycolytic

Muscle Adaptation to Exercise

Endurance training: More & bigger

mitochondria

More enzymes for aerobic respiration

More myoglobin

no hypertrophy

Resistance training: More actin & myosin

proteins & more sarcomeres

More myofibrils

muscle hypertrophy

Causes of FatigueCauses of FatiguePeripheral Fatigue

◦Arises between the neuromuscular junction and the contractile elements of the muscle

◦Ach depletion, neuromuscular junction receptor loss Myasthenia Gravis

Skeletal Muscle TypesSkeletal Muscle TypesFast-twitch muscle fibers (type II)

◦White Fibers Low Myoglobin

◦Develops tension two to three times faster than slow-twitch fibers

◦Splits ATP more rapidly to complete contraction faster

◦Fatigues quickly

Skeletal Muscle TypesSkeletal Muscle TypesSlow-twitch Muscle Fibers (Type I)◦Red◦High Myoglobin levels◦Slow to Fatigue

ContractionsContractionsIsometric Contractions

◦Creates force without movementIsotonic Contractions

◦Moves loads

During skeletal muscle contraction the During skeletal muscle contraction the binding of the myosin head to G-actin binding of the myosin head to G-actin occurs at which step?occurs at which step?

A. Cross bridgeB. Power strokeC. Working strokeD. Force stroke

During the cross bridge the myosin During the cross bridge the myosin head is in the ____ configuration.head is in the ____ configuration.

A. Low energyB. High energyC. Medium energyD. Power energy

Name the connective tissue Name the connective tissue layer that surrounds a fascicle layer that surrounds a fascicle in skeletal muscle.in skeletal muscle.A. EndomysiumB. EpimysiumC. PerimyseumD. TendonE. Epicardium

Name the functional unit of Name the functional unit of skeletal muscle.skeletal muscle.A. SarcolemmaB. Saroplasmic ReticulumC. SarcomereD. Myosin

The thick filament is also The thick filament is also referred to asreferred to asA. ActinB. MyosinC. TropomyosinD. Troponin CE. G Actin

Which protein in G-Actin is Which protein in G-Actin is responsible for blocking the bind responsible for blocking the bind site of myosin?site of myosin?A. TropomyosinB. Troponin CC. Sarcoplasmic ReticulumD. Sarcolemma

During skeletal muscle During skeletal muscle contraction Calcium is stored contraction Calcium is stored in thein theA. SarcolemmaB. SarcomereC. Sarcoplasmic ReticulumD. Golgi ApparatusE. Transverse Tubules

The build-up of potassium in the The build-up of potassium in the _______ causes the resting _______ causes the resting membrane potential of skeletal membrane potential of skeletal muscle to depolarize.muscle to depolarize.

A. SarcolemmaB. Sarcoplasmic reticulumC. Transverse tubuleD. Tropomyosin

Which enzyme is located on Which enzyme is located on the myosin head?the myosin head?

A. ATP synthaseB. ATP aseC. ATP reductaseD. PhophodiesteraseE. Oxidase

During cross bridge During cross bridge formation myosin will bind to formation myosin will bind to ________.________.

A. Troponin CB. TropomyosinC. G-ActinD. Myosin

The phenomenon of rigor The phenomenon of rigor mortis is a direct result ofmortis is a direct result of

A. The breaking of myosin bonds by ATP

B. The breaking of actin bonds by ATPC. The inability of the myosin cross

bridges to combine with single amino acids

D. The loss of ATP in dead muscle cells