Muscles Physiology

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 muscles 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, that ensure supplying of all cells and tissues with the needed
oxygen and nutrients, and getting rid of waste products as well, 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, those 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 common feature with skeletal muscle in being striated, but they are similar
to smooth muscles in being involuntary and communicating with each others 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 disks 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 sub-types 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 like gastrointestinal tract.
b. Multiunit smooth muscles: They consist of individual units, that are innervated and contract individually.
They found in the eye (iris), in the wall of large blood vessels, as well as at the base of hair follicle.
Cardiac and smooth muscles physiology would be discussed in details in lectures of cardiovascular and
digestive physiology respectively. In the recent lecture we will focus on the skeletal muscles physiology.

Characteristics of skeletal muscles:

Skeletal muscles - and muscles in general- have the following characteristics:
1- Excitability: This means that they respond to stimuli such as nervous impulses.
Skeletal muscles cannot contract without a nervous stimulus, coming from motor neuron.
Skeletal muscle communicates with motor nerve via neuromuscular junction, which action is similar to
synapses between neurons.
When a motor order in form of nerve impulse achieves the end bulb of the motor neuron, causing 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 causes influx of
sodium ions which leads to 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, as we will discuss shortly.
The effect of acetylcholine is lately terminated by an enzyme, called Acetylcholinesterase, which
degrades a part of acetylcholine, converting it into acetate group and choline. Choline will be recycled
later. The calcium then will be pumped back to the sarcoplasmic reticulum by Sarcoplasmic Reticulum
Calcium ATPase.

Clinical Physiology: (Students were asked to search for as a homework):

1. Myasthenia Gravis: An autoimmune disorder that is caused by produced 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 released 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.
4. Eaton-Lumbert Syndrome: Autoimmune disease which causes destruction of calcium channels on the
presynaptic neuron, which leads to impaired communication between motor neuron and muscle cell, and
thus causes muscle weakness.
5. Tetanus toxin: Also prevents the release of Acetylcholine from the motor neuron and thus causes
muscle weakness.

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.
Fascicle is 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 myofilaments ( 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 myofilaments (Actin): The thin filament is called actin. It is form of three proteins: Actin molecules
(G- Actin) is a spherical protein, which form two coil 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 cell (also called sarcolemma) is unique in that it has transverse tubules ( Ttubules) 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 pumps 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
dihydropyridin (DHP) receptor, which is a voltage sensor. When the action potential is conducted to the TTubule, it causes conformationalchangeinthementionedreceptor.Thischangeactivatesareceptor,
calledryanodinereceptor,whichwillcausereleaseofcalciumfromthesarcoplasm.

Now,afterweunderstoodthestructureoftheskeletalmuscle,wecanexplainhowitcontracts:
Musclecelltocontracthastoreceiveanerveimpulse(avoluntarymuscle).Whenthenerveimpulsereachesthe
plasmalemmaandpassdowntheTTubules,itcausesopeningofthecalciumpumpsinthesarcoplasmicreticulum
andreleasingofcalciumwithinthemyofilaments.CalciumionsthenattachtotheTroponinCandcauseschangesin
shapeandpositionofTroponin,whichwillmovetheTropomyosin,whichisattachedtoTroponin;thisinturnwill
uncoverthemyosinbindingsiteonActinmolecule(Gactin).Thiswillenablethemyosinheadtoconnecttoactin
andswivel;thiswillpulltheactinforward.
Herewehavetonoticethatmanymyosinheads(notonlyasinglehead)swivelinthesametime,pullingtheentire
thinfilamentforward.
ATPmoleculebindtothemyosinheadattheendofswivel,breakingthebondbetweentheactinandmyosinandthe
myosinswivelbackward.ThiswouldbreaktheATPintoADPandorganicphosphatePi,whichcausesthemyosin
tobindtoanewactinmoleculeandswivelforwardagain.Theendresultofthisseriesofprocessesisshorteningof
theSarcomere.
Whenthenervousimpulsestops,themusclerelaxes.Intheabsenceofnerveimpulse,thereisnoreleaseofcalcium.

ClinicalPhysiology:Rigormortisisasigndeath,whichispresentedasamusclestiffnessofthecadaver,dueto
inabilityofmusclestorelax,becausethelackofATP,whichproductionisstoppedafterdeath,becausethe
metabolismisterminated.
Typesofmusclecontractions
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 an object at a constant speed.
When the muscle tension increases to meet the resistance and then become 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. So, contraction of muscle does not only express as shortening of muscle fibers. Lengthening
of muscle fibers as occurs in eccentric isotonic contraction.
2- Isometric contraction: in such contraction, there is an increase 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 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 sustains contraction for only 5 second.
2. Glycolysis: Generation of 2 ATP molecules as a result of anaerobic catabolism of glucose in the
cytoplasm. It sustains muscle contraction for 1 minute, but causes lactic acid accumulation, which leads
to muscle fatigue.
3. Oxidative phosphorylation: Generation of 38 ATP molecules as a result of glucose catabolism in
mitochondria 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, also known as slow 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 much mitochondrion.
2- Type II, also known as fast fibers (or white fibers): Their white appearance is 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 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.
For more explaining:
In case of stretched muscle, There is a reduced overlap between actin and myosin, so, the
number of cross linkage is reduced.
When muscle fiber length is shorter than the optimal, there is no enough distance the actin
filaments can move.

Mechanics of smooth muscle contraction

Smooth muscle cells are small ones with spindle shape. Their myofilaments are not arranged in
Sarcomere and not identical to those in skeletal muscle. Instead their Z-line they are anchored to a
dense body of intermediate filaments (neither thin nor thick).
They don`t have Troponin. They don`t have neither T-tubules, nor well-developed and extensive
sarcoplasmic reticulum.
There are two types of smooth muscles:
Unitary smooth muscle: found in hollow organs like gastrointestinal tract, uterus, and urinary tract.
Muscle fibers are connected with much gap junctions and contract as a syncytium.
Multiunit smooth muscle: individual muscle fibers with decreased number of gap junctions or with
no gap junctions at all. They are found in iris of the eye, large blood vessels, and
As in skeletal muscle calcium ions play an important role in smooth muscle contraction but in different
way. Most of calcium comes from extracellular fluid. 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 then gets removed from myosin by another enzyme (myosin light chain phosphatase), after the
calcium has pumped out of the cell. Calcium is pumped out via either ATP dependent calcium pumps or
by sodium-calcium exchanger.
We have to notice here that dephosphorylation is not the only cause of smooth muscle relaxation. There
are other mechanisms that assist relaxation like dissociation of Ca++-calmodulin complex.

Smooth muscle contraction and relaxation could be affected by autonomic nervous system and by
hormones and humeral factors.

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