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HOW A MUSCLE FIBER CONTRACTS????

Sarcomeres = functional units of a skeletal muscle fiber.

Each myofibril contains thousand of sarcomeres

The thick filaments lie in the center of the sarcomere.

The thin filaments are attached to either end of the sarcomere & extend towa

the center & passing among the thick filaments.

The arrangement of thin & thick filaments within sarcomere produces the stripappearance of a myofibril.

As a results, the entire muscle fiber has banded/striated appearance.

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Sliding of the thin filaments toward the center of the sarcomere causes the

unit to shorten or contract.

This explaination of muscle contraction is called the sliding filament model.

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What causes filament sliding????

Sliding occurs after the cross-bridges, or head of the thic

filaments attach to the thin filaments.

Each cross-bridges then pivots at its base, pulling the thin filamenttowards the center of the sarcomere.

This pivoting, shortens the sarcomere is called a power stroke.

A molecule of ATP must bind to the myosin head before it can detacfrom the thin filament; the ATP will be used for the next powestroke.

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What triggers a contraction????????????

Cross-bridges formation can occur only in the presence of calcium ions (Ca2+)

Ca2+ - stored in the endoplasmic reticulum of the muscle fiber.

Ca2+ - released into sarcoplasm when 1/> electrical impulses travel across themuscle fibers, in response to the arrival of neurotransmmiter at themotor end plate.

Ca2+ - pumped back into endoplasmic reticulum as soon as the impulse/s ceasedthis active process required ATP.

The muscle contraction ends when Ca2+ level in sarcoplasma return to normal lolevel.

Each time ATP is broken down, some energy is released as heat.

Muscle contractions release large amount of heat responsible for maintainingbody temperature.

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WHAT IS RIGOR MORTIS??

When death occurs, circulation stops, and the skeletal muscles are deprived of

nutrients and oxygen.

Within a few hours, the skeletal muscle fibers have run out of ATP, & theendoplasmic reticulum becomes unable to remove Ca2+ from sarcoplasm.

Ca2+ diffusing into the cell from the extracellular fluid or leaking out of their

storage area then trigger a sustained contraction.

Without ATP, the myosin cannot detach from the cross-bridges, and themuscles locks in the contracted position.

All the bodys skeletal muscles are involved, and the individual becomes stiff

This physical state, called rigor mortis, lasts until the muscle fibers begin todecompose 15 25 hour later.

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CONTRACTION OF SKELETAL MUSCLE

contract only under the control of the nervous system

Communication between the nervous system and a skeletal muscle fiberoccurs at neuromuscular junction (NMJ), or myoneural junction

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A narrow space, the synaptic cleft, separates the synaptic terminal of theneuron from the opposing sarcolemmal surface.

The synaptic cleft and sarcolemma also contain the enzymeacetylcholinesterase(AChE), or cholinesterase, which breaks down ACh.

This surface (motor end plate), contains membrane receptors that bind ACh.

The Neuromuscular Junction (NMJ)

Each skeletal muscle fiber is controlled by a neuron at a single NMJ

A single axon branches and ends at an expanded synaptic terminal

The cytoplasm of the synaptic terminal contains mitochondria and vesicles filwith molecules of acetylcholine (ACh).

ACh trigger the contraction of the muscle fiber.

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(1)

(2) (3) (4)

(5)

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Interference With Neural Control Mechanisms

Bacteria, Spiders, Snakes & U

What do the bacteria {Clostridium botulinum}, black widow

spiders, cobras and humans have in common??????

They all produce toxins, that attack the chemicalsynaptic transmission which occurs at NMJ

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Botulismis caused by the neuro- toxin botulin, which is produced by thegrowth of C. botulinum in improperly canned foods.

"Botulism comes from the Latin word for "sausage' because of the earlyassociation of the disease with poorly preserved meat

Botulin is a very potent blocker of neuromuscular transmission;

As few as 10 molecules of the toxin are enough to inhibit a cholinergicsynapse.

It is believed that botulin inhibits the release of ACh at the NMJ, leading ta potentially fatal muscular paralysis

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Black widow spider venom also exerts its deadly effects by affectingtransmitter release.

The venom first increases, and then eliminates, ACh release at theneuromuscular junction

The bite of the cobra also results in the

blockade of neuromuscular transmission inits victim.

The active compound in the snake's venom,called cobratoxin, is a peptide molecule

that binds tightly to the postsynapticreceptors and prevents their activation byACh.

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Humans have synthesised a large number of chemicals that poison synaptic

transmission at the neuromuscular junction.

Originally motivated by the search for chemical warfare agents, this effortled to the development of a new class of compounds called organophosphates.

These are irreversible inhibitors of AChE, and by preventing the degradationof ACh, they probably kill their victims by causing a desensitisation of AChreceptors.

The organophosphates used as insecticides, like parathion, are toxic tohumans only in high doses.

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Myasthenia gravis

Myasthenia gravis is an autoimmune disease [cause is a misguided attackon the ACh receptors by the immune system]

Results in the loss of ACh receptors at the junctional folds

The name is derived from the Greek for severe muscle weakness.

The disorder is characterised by weakness and fatigability of voluntarymuscles, typically including the muscles of facial expression, and it can befatal if respiration is compromised.

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ENERGY SOURCES FOR CONTRACTION

A resting muscle fiber contains only enough ATP and other high-energycompounds to sustain a contraction until additional ATP can be generated.

During contraction, the muscle fiber will generate ATP at the same rate as itis used.

A single muscle fiber contain ~ 15 billion thick filaments.

When actively contracting, EACH thick filament breaks down ~ 2500 ATPs/sec

Even a small skeletal muscle contains thousands of muscle fibers, the ATPdemands of a contracting skeletal muscle are enormous.

the demand for ATP in a contracting muscle fiber is so high

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At rest, a skeletal muscle fiber produces more ATP than it needs.

Under these conditions, ATP transfers energy to creatine to form another high-energy compound, CP, or phosphorylcreatine:

ATP and Creatine Phosphate (CP) Reserves

ATP

ADPCreatine

phosphate

muscle

relaxed Creatine

creatinephosphokinase

(CPK)

** [CPK]blood serious muscle damage **

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During a contraction, each myosin cross-bridge breaks down ATP, producing ADPand a phosphate group.

The energy stored in creatine phosphate is then used to "recharge" ADP,

converting it back to ATP through the reverse reaction:

ATP

ADPCreatinephosphate

Creatine

Contractingmuscle

Energy fmuscle

contracti

creatinephosphokinase

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A resting skeletal muscle fiber contains ~ 6X as much CP as ATP.

When a muscle fiber undergoing a sustained contraction, these energy reserves arexhausted in only about 17 sec.

the muscle fiber must then rely on other mechanisms to convert ADP to ATP

Other mechanismsAerobic metabolism [ in mitochondria]

Glycolysis[in cytoplasm]

(anaerobic)

Anaerobic metabolism

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Anaerobic metabolism

Aerobic metabolism

produce 36 ATPs / glucose molecu

{2 ATP in glycolysis + 2 pyruvic acid inaerobic metabolism (34ATP)}

Produce 17 ATPs/molecule fed/cycle

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EnergyStored as

Utilisedthrough

InitialQuantity

Number ofTwitchesSupportedby EachEnergySourceAlone

Duration ofContractionSupported byEach EnergySource Alone

ATP ATPADP + P

3 mmol 10 2 sec

CP ADP + CPATP + C

20 mmol 70 15 sec

Glycogen Glycolysis

(anaerobic)

100 mmol 670 130 sec

Aerobicmetabolism

12,000 2400 sec (40 min)

Sources of Energy Stored in a Typical Muscle Fiber

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When glycolysis produces pyruvic acid faster than it can be utilised by themitochondria, pyruvic acid levels rise in the sarcoplasm.

Under these conditions, the pyruvic acid is converted to LACTIC ACID.

Anaerobic energy production has its drawbacks:

lactic acid - lower the intracellular pH.

Changes in pH will alter the functional characteristics of keyenzymes.

The muscle fiber will then become unable to continuecontracting

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Muscle Fatigue

A skeletal muscle is considered fatiguedwhen it can no longer contract, despitecontinued neural stimulation.

Can be due to :

exhaustion of ATP and CP reserves

drop in pH {buildup of lactic acid}

interruption in blood supply/lack of neurotransmitter (rare)

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In the recovery period, conditions inside the muscle fibers gradually returned tonormal, preexertion levels.

It may take several hours to a week

Muscle Recovery

When a muscle fiber contracts:-

Energy reserves consumed

Heat released

lactic acid generated

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During recovery period, the bodys O2 demand increases.

The extra O2 is used by mitochondria in;

HEPATOCYTES

ATP is required forconversion of lactic acid to

glucose

MUSCLE FIBERS

ATP is needed torestore ATP & glycogen

reserves

The additional O2 required during recovery period is called the oxygen debt.

How to pay????

the rate & depth of breathing