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2

Ahmad Ar'ar

Muhammad Abed

Mohammad Khatatbeh

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Muscle Physiology

we start talking about the structure of skeletal muscles and the Before

process of contraction, here is a reminder of how we classify muscles in

.our body

We can classify muscles in our body to two main types:-

.Cardiac Muscles and Skeletal Musclesinclude both Striated Muscles: -

- Smooth Muscles: we will talk more about them in the introduction of

the GI System.

So, we have three types of muscles in our body

(smooth/skeletal/cardiac) that are classified into two main groups

shown above according to the way they look under the

microscope.(there are other ways of classification).

Note: even though skeletal and cardiac muscles are both striated

muscles, there are some differences between them. For example and

not limited to, there are functional and structural differences, as well as

differences in the action potential (ex: type of ions).

Structure of skeletal muscles

Any muscle is composed of many fibers(cells), but here, we will be

specifically discussing the ultra-structure of these fibers in the skeletal

muscles.(even smooth muscles are made up of fibers, so the striation

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isn’t at the level of the whole muscle, it's at the level of the fibers that

form the muscle).(more details later)

Some Terminology before we start:

* Muscle fiber = Muscle cell = Myofiber

* Nerve fiber = axon of neuron

Note: nerve fibers (axons) have many terminals; each terminal will

synapse with one muscle fiber. (So 1 terminal of certain nerve fiber will

synapse with 1 muscle fiber)

We will start with a general overview of the structure (larger to smaller):

bundle of Skeletal muscle

(fascicle)muscle fibers

functional units myofibrils

" that contains sarcomerecalled "

actin and myosin filaments.

So, as we can see, skeletal

muscles are made up of many

fibers, inside each of these fibers

cylindrical like there are many

contractile filaments called myofibrils, these fibrils contain structures

(actin and myosin) organized in functional units called sarcomeres, these

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repeated sarcomeres are responsible for the striated appearance of

skeletal muscles under microscope.

:Sarcomere in details

and forms the basic tissueSarcomere is the basic unit of striated muscle

.contraction muscle machinery necessary for

This figure is actually a part of the myofibril; it's an organization of

filaments in darker and lighter regions that give us the striated

appearance. From the figure, we can notice the following:-

(I for isotropic) and contain only one type I band: called Lighter region -

of filaments: the actin (thin) filaments.

(A for anisotropic) and contains the entire A band: called Darker region -

length of a single thick filament. (It’s the region where thick filaments

are positioned whether overlapped with thin filaments or not).

only A band that contains "DARK" region within the LIGHT :H zone -

As opposed to the H (no overlapping with actin). thick (myosin) filament

zone, the remaining part of the A band shows overlapping between actin

and myosin, and for that reason, it's actually the darker region.

- Z disc/line: it’s a line/disc in the middle of the I band that holds the

actin (thin) filaments in position. (Line or disc according to the way we

are viewing it whether its 2d or 3d, if 2d its line, 3d its disc).

- M disc/line: it’s the line/disc in the middle of the H zone that holds

myosin (thick) filaments in position. (It's actually in the middle of the A

band and thus in the middle of the sarcomere as well)

Note: near the M line there are only thick filaments (H zone) and near

the Z line there are only thin filaments.

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- Sarcomere: an individual sarcomere extends from one Z line to the

next Z line. (sarcomere: it's very ends contain only thin filaments, its

center only thick, otherwise, there is an overlap between the two, and

this region where the overlapping occurs is actually a part of the A

band).

In the regions where overlapping between actin and myosin occurs, we

find that each thick filament is surrounded by six thin filaments, and

each thin filament is surrounded by only three thick

filaments, so the ratio of thin:thick is actually 2:1

The cross section in the right shows that ratio.

Now, after we viewed the ultra-structure of myofibrils, we should have a

clearer idea about the striation of skeletal muscles. Just to make sure

you’ve got it right, here is the main concept:

What we mean by striation isn’t actually that Muscles are made up of

those myofibers aggregated in bundles (isn’t at the level of the whole

muscle), its actually related to the structure of each fiber made up from

myofibrils with filaments arranged in repeated sarcomeres (so it's at the

level of 1 muscle fiber).

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-:Other functional structures

- Sarcoplasmic Reticulum

It’s a specialized type of smooth ER that

regulates the calcium ion concentration in

.the cytoplasm of striated muscle cells

Transverse Tubules -

e junctionat thMembranous structures running in transverse direction

.I band the A band andthe between

transmission of action potential and in a role in the : T. tubules haveNote

explained more in later regulating cellular calcium concentration (will be

).lectures

We can notice from the figure what's called

.TRIAD

formed by a T tubule So Triad is a structure

with a sarcoplasmic reticulum (SR) known as

.on either side (sacs) the terminal cisterna

).Triad 3 elements T.tubule acs and 1S 2(

we have two additional differences between skeletal and level,At this

-:whice are cardiac muscles

:Location of the Transverse Tubules -

.at the junction between the A and I bands Skeletal muscles

.near the Z disc Cardiac muscles

:Diad/Triad -

.Triad of 1 T.tubule and 2 sacs Skeletal muscles

.tubule with 1 sac onlyDiad of 1 T. Cardiac muscles

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Ultra structure of actin and myosin

:)filaments (actin Thin filaments

Made of three basic components which

protein molecules actin -are:

troponin (regulatory) -

tropomyosin (integral part, regulatory) -

actin alpha helixThese actin protein molecules polymerize to form the

of the thin filaments. Then, the regulatory backbonewhich forms the

proteins Troponin and Tropomyosin are added to form the actin (Thin)

summarizes that) belowfigure . (Thefilament

is a binding site to We can notice that within each actin molecule, there

notice that the whole structure of the thin we ,Also attach with myosin.

, and that this tropomyosin is filament is covered by tropomyosin

. blocking the binding site at normal conditions

are actually made up of three regulatory subunits, Troponin molecules

:these subunits are referred to as C, T and I

.bindingalcium Cfor :CTroponin -

.ropomyosinTfor connection with : TTroponin -

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.ntermediate between C and TI: ITroponin -

:filaments)Thick filaments (myosin

Composed of myosin molecules, each molecule

is composed of two globular heads and a tail

)moleculehe figure shows the structure of a single myosin T(

forms an alpha helix that is actually the Tail: -

.backbone

protruding outside two globular heads Heads: -

Each head has two and forms the cross bridges.

.Actin binding site (binds with the binding site of actin) -sites:

Myosin ATPase site (enzymatic activity that splits ATP into -

.)ADP and Pi

So actually for each single myosin molecule, we have 2 heads, for

each head we have two sites, so totally we have 4 sites/molecule;

.binding sites and 2 ATPase sites 2

Sliding filament theory based on muscle muscle contraction Explains the mechanism of

It's .proteins that slide past each other to generate movement

actually the slide of thin filaments over thick filaments towards

entre of sarcomere, resulting in the shortening of the the c

.sarcomere and the contraction of the muscle

Interaction between actin and myosin

:General overview

Troponin C, ) must bind to +2To get interaction, Calcium ions (Ca

changes in the regulatory upon that binding, conformational

proteins and Tropomyosin occur, resulting in the displacement of

, away from the binding site of the Actin molecules Tropomyosin

thus exposing these sites so they become available for interaction

prevents . (In the normal state, what with myosin heads

is that Tropomysin is covering the binding sites of interaction

).actin

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So again, at low Calcium concentrations

(resting state), binding sites of actin

filaments will be covered by Tropomyosin, and no interaction

urs. Once the concentration is increased enough, occ

ill be biding sites of actin w and thees occur gconformational chan

exposed to interact with the binding sites of

.myosin

:Detailed Steps of Contraction

general overview, here is the detailed process of theAfter

:contraction, explained as sequential steps

Calcium ions bind to the )1

nin C subunit resulting in Tropo

conformational changes that

.expose the binding site of actin

Myosin heads (specifically actin ) 2

binding sites) bind to and attach

, with the binding sites of actin

. (Here the forming cross bridges

myosin heads should be in the ADP and Pi configuration,

).explained more later on

Power stroke: each binding process is followed by an automatic ) 3

ational change (change in position) of the myosin heads conform

that results in the bending process towards the center of the

.sarcomere. This bending process is known as the power stroke

Detachment: the cross bridges detach when the myosin heads ) 4

TP, replacing ADP and Pi that were present in the bind to new A

initial state. (Explanation right after the steps)

broken ATP: the newly bound ATP molecule will be ofSplitting ) 5

energizing the head -down by the ATPase site to ADP and Pi, re

.ready for another interactionback to its initial state,

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kept high, the are sAs well as the calcium ion concentration) 6

d again to get shorter and shorter cycle will be repeated again an

sarcomeres. Once the concentration decreases, the interaction

osin heads are in the ready / will stop even though the my

energized state. (Binding sites of actin are covered thus no

).contraction

:Some notes and explanations

For interaction between myosin and actin to occur, the myosin -

and Pi heads should be energized by binding with ADP

makes the affinity between actin and . Pi (phosphorylated heads)

have Pi and have ATP myosin high enough for binding. Unless we

interaction will take place as the affinity is low, and , no instead

.oundthat explains why detachment occurs when new ATP is b

For relaxation to occur, we should have a decrease in Calcium -

.concentration inside the cell

needs 1 ATP each cycle for detachment first of head single Each -

.energized by splitting that new ATP-all and then to be re

state, even though we have high affinity In the resting/relaxed -

contraction will no (energized myosin heads), no interaction and

tin are covered by take place because the binding sites of ac

.Tropomyosin

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no new ATP for detachment, the muscle will stuck in isIf there -

the contractile position, no relaxation. This takes place normally

, a 6 h) after death due to the absence of fresh ATP-few hours (4

.state called Rigor Mortis (contractures)

ion is a little bit complicated, and the Magnesium role in contract -

doctor said if you want to understand it you should be involved in

:research, but briefly and simply, we can say that

.It's needed for the ATPase activity -

th ATP for Its needed to remove ADP and replace it wi -

.contractures/spasm) detachment (low Mg

needed for the ATPase pumps of Calcium to allow the It's -

.pumping back to SR) (calciummuscle to fully relax

Two enzymatic activities actually affect the heads of myosin; -

that removes phosphatasethat adds Pi on the head and ATPase

.that Pi

:Sarcomeres' changes during contraction

becomes shorter H zone

becomes shorter I band

becomes shorter Length of the sarcomere

.The distance between two Z lines decrease -

NO CHANGE A band

of thick filaments, and since we A band resembles the length -

are only having sliding between actin and myosin, there is no

change in the length of the thick filaments, thus no change in

.A band

(2 video that I recommend everyone to watchHere is a very useful

:)minutes only

https://www.youtube.com/watch?time_continue=158&v=dGqJtta

HBvk

Summary from the doctor:

GneonFlcZG8https://www.youtube.com/watch?v=

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Muscle Energy

As we have seen, we need ATP molecules for the process of

contraction at certain steps, these ATP molecules have different

:sources at different intervals of time

found already in the muscle ATP moleculesThe first source is ) 1

(we need high ATP/ADP for contraction), but this source provides

?, so how we can replenish ATPfew secondsATP for only

For continuous muscle activity, we need to replenish that ATP, ) 2

Creatine ompounds called are c sand the source in skeletal muscle

energetic molecules that -. These compounds are microphosphate

are used by specific enzymes that transfer the phosphate group to

an ADP molecule to form ATP and creatine. Creatine phosphate is

fic pathways and activities. then replenished from creatine by speci

few This source actually provides energy that is enough for only

(Check the figure at the end) minutes.

Then we have additional sources, either anaerobic (glycolysis) ) 3

.or aerobic (oxidative phosphorylation)

.(this method forms Lactic Acid) aster but less ATPGlycolysis: f -

.Oxidative phosphorylation: slower but more ATP -

muscles to Fast and skeletal we can classify ,According to that

:Slow muscles

depend more on glycolysis, also called white Fast muscles:

.muscles

depend more on oxidative phosphorylation, they Slow muscles:

they store it in Myoglobin. thus andprocess for that need oxygen

these slow and sored, it isMyoglobin is similar to Hemoglobin,

more As these muscles need muscles are called red muscles.

., they are highly vascularizedoxygen

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we have different skeletal muscle fibers to give different ,So

functions. These different types (fast/slow) have different

they are ;functional differences the characteristics other than

, presence of gical views, energy viewsdifferent in the histolo

mitochondria (we have more mitochondria in slow muscles),

.etc …vascularization (red muscles are vascularized more)

Example mentioned by the doctor about the functional

ons have more slow differences: players who participate in marath

. Those who participate in short races have more fastsmuscle red

. If either one tried the opposite sport, he won't smuscle white

(Check the table below for comparison) function effectively.

Respiration (oxidative NOTE: when we have insufficient Aerobic

and the Anaerobic glycolysis process ),phosphorylation

lactic acid than it should be, we end up with predominates more

accumulation. In light activities, we can cope with the situation,

and spasms. but in strenuous ones, we will end up with pain

).call it as Muscle Fatigue Some(

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.figure for muscle energy from the doctors slides