Muscle

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● Muscular system is the system that enables us to move as our muscles are

connected to bone by tendons.


● Tendons are connective fibers that attach muscles to bone and cause the movement
of bones when muscles contract.
● About 85% of muscle work is heat production , while the remaining 15% is physical
work , so they play an important role in thermoregulation of our organism.
● They also maintain posture and protect the other organs and tissue .
● Cardiac muscle causes blood pumping , which ensures supplying of all cells and
tissues with the needed oxygen and nutrients , while the smooth muscles that line the
hollow organs ensure many other functions such as : blood flow , digestion , urine
outlet , respiration , and reproductive functions.
Types of muscles
● There are three types of muscles in the human organism:
● 1- Skeletal muscles : Striated , voluntary , multinuclear , that cause body movement ,
maintaining posture , heat production , and organ protection. We will discuss the
physiology of skeletal muscles in this lecture.
● 2- Cardiac muscles : They have a common feature with skeletal muscle in being
striated , but they are similar to smooth muscles in being involuntary and
communicating with each other via gap junctions.
● Cardiac muscles are connected to each other by desmosomes to prevent rupturing
under the continuous physical stress. Both desmosomes and gap junctions are found
in the intercalated discs between cardiac muscle cells.
● 3- Smooth muscles : Lines the hollow internal organs . They are not striated ,
involuntary muscles that participate in most functions of other systems , such as ;
digestion , blood flow , respiration , reproduction and others.
● There are two subtypes of smooth muscles:
● a. Unitary smooth muscles : These smooth muscles have multiple muscle fibers that
contract as one unit , due to gap junctions that connect them and facilitate traveling
of impulse from cell to cell. They found in the walls of hollow organs
● b. Multiunit smooth muscles : They consist of individual units that are innervated and
contract individually . They are found in the eye ( iris ) , in the wall of large blood
vessels , as well as at the base of the hair follicle.

Characteristics of skeletal muscles


● Skeletal muscles - and muscles in general- have the following characteristics:
● 1- Excitability : which means that they respond to stimuli such as nervous impulses.
● Skeletal muscles can not contract without a nervous stimulus , coming from motor
neurons .
● Skeletal muscle communicates with motor nerves via neuromuscular junction , which
action is similar to synapses between neurons.
● When the motor order in the form of nerve impulse achieves the end bulb of the
motor neuron , it causes the opening of calcium channels and influx of calcium inside
the neuron. This would lead to condensation of neurotransmitter vesicles and fusion
of vesicles with the cell membrane , and then releasing of neurotransmitter (
acetylcholine) into the neuromuscular cleft.
● Acetylcholine then binds to nicotinic cholinergic receptors on the plasmalemma ( cell
membrane of the muscle cells) . This will increase the permeability of the
plasmalemma to sodium ions and cause depolarization of the plasmalemma . If the
depolarization reaches the threshold , an action potential will develop and a series of
reactions will take place inside the muscle cells , leading to muscle contraction.
● The effect of acetylcholine is terminated by an enzyme , called Acetylcholinesterase ,
which degrades a part of acetylcholine , converting it into acetate group and choline .
Choline will be recycled later .

Clinical Physiology
● 1. Myasthenia Gravis : An autoimmune disorder that is caused by immune system
antibodies that mask the nicotinic acetylcholine receptors and cause muscle
weakness.
● 2. Black widow spider venom involves a component , which is known as latrotoxin .
This toxin causes increased release of acetylcholine and stimulates severe and
painful muscle cramps.
● 3. Botulinum toxin prevents the release of acetylcholine from the end plate of the
motor nerve and thus causes muscle paralysis.

● 2- Contractility : Means the ability of skeletal muscle to shorten in length . We can


understand this characteristic after studying the structure of the skeletal muscle , as
follows :
● Skeletal muscle as an organ is evolved by a connective tissue sheet , which is known
as epimysium . The skeletal muscle fibers within the epimysium are composed of
many subunits ( bundles ) , each of which is called muscle fascicle . Each fascicle is
covered by a connective tissue , called perimysium.
● Fascicles are composed of numerous muscle fibers , each fiber is actually a muscle
cell . Muscle fiber is also sheeted by a connective tissue , called endomysium.

● The muscle fiber (cell) is composed of many myofibrils , which are made up of long
proteins , called myofilaments . There are two types of myofilaments :
● a- Thick myofilament ( Myosin) : The thick filament is composed of a protein called
myosin , which has a core tail , and a head , which is a projection from the tail .
● The head has two binding sites : one for actin molecule and other for ATP molecule
.It has a hinge ( neck) at the point , where it leaves the tail. The hinge of the myosin
head allows the head to swivel back and forth which causes muscle contraction.

● b- Thin myofilament ( Actin) : The thin filament is called actin . It is formed of three
proteins : Actin molecules ( G- Actin) is a spherical protein , which form two coils on
each other protein chains , Tropomyosin: molecules are thin proteins that wrap the G
Actin and cover the binding sites of myosin in the relaxing state of skeletal muscle ,
and Troponin molecules ( Troponin C , Troponin I and Troponin T) , which are small
proteins that are connected to each other and form troponin complex , which have
binding sites for calcium ions.
● The myofilaments in skeletal muscles are arranged in a specific pattern , called
Sarcomere . In Sarcomere a thick filament ( myosin) is surrounded by six thin
myofilaments ( actin) . But in a side view , each actin appears to be above and under
myosin. . In sarcomere the thin filaments extend to the end of the sarcomere , where
the adjacent thin filaments are connected by Z-line ( composed of different type
protein) , while the thick filaments remain in the center and not extend to the end of
sarcomere . This is the cause for the striated appearance of skeletal muscle under
the microscope , as the ends of sarcomere ( I bands ) appear lighter than the center (
A band ).

● The cell membrane of muscle cells ( also called sarcolemma ) is unique in that it has
transverse tubules ( T- tubules) which pass down the cell and open in the
endoplasmic reticulum of the muscle cell.
● Endoplasmic reticulum of the muscle cell ( known as sarcoplasmic reticulum) is
different in that it functions as a store for calcium ions , more than being involved in
protein synthesis .
● The membrane of the sarcoplasmic reticulum has many calcium pumps that pump
calcium inside the sarcoplasmic reticulum from the sarcoplasm ( cytoplasm of the
muscle cell ). Sarcoplasmic reticulum is abundant in the muscle cells , and is closely
associated with the myofibrils.
● T- Tubules of the sarcolemma are connected to sarcoplasmic reticulum by receptor
protein , known as DHP receptor , which is a voltage sensor. When the action
potential is conducted to the T- Tubule , it causes conformational change in the
mentioned receptor . This change activates a receptor , called ryanodine receptor ,
which will cause release of calcium from the sarcoplasm .

● Now, after we understood the structure of the skeletal muscle , we can explain how it
contracts:
● Muscle cells to contract have to receive a nerve impulse ( a voluntary muscle) .
When the nerve impulse reaches the plasmalemma and passes down the T-Tubules ,
it causes opening of the calcium pumps in the sarcoplasmic reticulum and releasing
of calcium within the myofilaments. Calcium ions then attach to the Troponin and
causes changes in shape and position of troponin , which will move the Tropomyosin
, which is attached to Troponin, this in turn will uncover the myosin binding site on
Actin molecule ( G actin) . This will enable the myosin head to connect to actin and
swivel , this will pull the actin forward.
● Here we have to notice that many myosin heads ( not only a single head ) swivel at
the same time , pulling the entire thin filament forward.
● ATP molecule bind to the myosin head at the end of swivel , breaking the bond
between the actin and myosin and the myosin swivel backward .This would break the
ATP into ADP and organic phosphate Pi, which causes the myosin to bind to a new
actin molecule and swivel forward again. The end result of this series of processes is
shortening of the sarcomere.
● When the nervous impulse stops , the muscle relaxes . Because in the absence of
nerve impulse , there is no release of calcium.

Clinical Physiology
Rigor mortis is a sign of death , which is presented as a muscle stiffness of the cadaver , due
to inability of muscles to relax , because of the lack of ATP , which production is stopped
after death , because the metabolism is terminated.

Types of muscle contractions


There are two types of muscle contraction:
● 1- Isotonic contraction : The muscle length shortens , while the muscle tension
remains the same . An example of isotonic contraction is lifting a n object at a
constant speed. When the muscle tension increases to meet the resistance and then
becomes constant after shortening of muscle fibers , this isotonic contraction is called
concentric isotonic contraction. But when the muscle lengthens because the
resistance is greater than the power of the muscle , this is called eccentric isotonic
contraction.
● 2- Isometric contraction : in such contraction , there is an increased muscle tension ,
without changes in the muscle fiber length. Example : when carrying an object in
front of you .

3- Extensibility : Muscles are able to stretch when they are pulled . The level of extensibility
depends on many factors within the muscle itself , including the connective tissue , the
muscle mass , and others.
4- Elasticity : Muscles are able to return to their original shape and length after contraction or
extension .

Sources of energy for muscle contraction


Muscle uses ATP for its contraction , but ATP , that is stored in muscle is rapidly depleted
and needed to be regenerated .There are three sources for energy regeneration in skeletal
muscles:
● 1. Creatine Phosphate : Dephosphorylation of creatine phosphate release ATP . ATP
released by dephosphorylation of creatine phosphate sustain contraction for 5
seconds.
● 2. Glycolysis : Sustain muscle contraction for 1 minute , but causes lactic acid
accumulation , which leads to muscle fatigue .
● 3. Oxidative phosphorylation : In the presence of oxygen , the ATP released can
sustain muscle contraction for several hours.

Types of muscle fibers


● Muscle fibers can be categorized depending on the degree of oxidative
phosphorylation into two groups :
● 1- Type I fibers ( or red fibers) : The red appearance of these fibers due to the
presence of myoglobin . They use oxidative metabolism to generate ATP , so they
are slow to fatigue and suited for endurance exercise ( such as long running) . They
have a lot of mitochondria.
● 2- Type II ( or white fibers ) : Their white appearance due to the absence of
myoglobin . They use both oxidative metabolism and anaerobic metabolism , so they
are rapid to fatigue and suited for short bursts of power and speed ( sprinting for
example) . They have few mitochondria.

Physics of Skeletal muscles


● I. Muscle twitch and summation:
Muscle twitch is the response of a skeletal muscle to a single stimulation . It has three
periods :
1. latent period : involves the time of signal transmitting through the sarcolemma , including
T-tubules , and then reaching the sarcoplasmic reticulum , and releasing of calcium. No
contraction occurs.Duration : 4 ms.
2- contraction period : Period of contraction , duration is about 25 ms in skeletal muscles.
The tension increases during this period.
3- relaxation period : Duration is also about 20 ms in skeletal muscles . The tension
decreases during this period. The sarcolemma repolarizes and the calcium returns to the
sarcoplasmic reticulum.

If a second stimulus affects the muscle on the top of the first one before relaxation is
complete , it will contract with more force . This is called wave summation .

If many stimuli (2-5/s) affect the muscle fiber before relaxation is complete , the muscle
contraction will increase with each stimulus . This is called staircase phenomena ( or
incomplete tetanus ) . If the stimuli are more than that ( 20/s ) the contraction will reach its
maximum and the staircase will fuse in a smooth curve ( complete tetanus).

A stronger contraction may occur if more motor-units are involved . Motor unit means : the
motor nerve and muscle fibers , innervated by it . Involving of more motor units to achieve
stronger contraction is called motor-units summation

II. Length- tension relationship:


Optimal length of a muscle fiber means : a length , at which the fiber develops the greatest
tension. If the length of muscle fiber is less than , or more than the optimal length , it will not
be able to contract.

Mechanics of smooth muscle contraction


Smooth muscle cells are small ones with spindle shape . Their myofilaments are not
arranged in sarcomere . Instead their actin are anchored to a dense body of intermediate
filaments ( neither thin nor thick) .
They don't have troponin . They don't have either T-tubules ,nor well-developed
sarcoplasmic reticulum .
As in skeletal muscle calcium ions play an important role in smooth muscle contraction but in
different way :
Because lack of troponin calcium ions that come from out of the cell or from the
sarcoplasmic reticulum bind to ( calmodulin-myosin light chain kinase -MLCK ) , which is an
enzyme complex on the myosin . This enzyme complex breaks ATP into ADP and Pi. The Pi
is then transferred to myosin and activates it.
Myosin is then cross-bridge with actin and the muscle contracts .
The Pi is removed from myosin by another enzyme after the calcium has pumped out of the
cell. Calcium is pumped out via either ATP dependent calcium pumps or by sodium-calcium
exchanger.

Smooth muscle contraction is very slow ( duration: 3 seconds)

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