Human Physiology

These notes are intended to accompany lectures in Human Physiology by Dr. Peter King at Francis Marion University, Florence, SC 29502.


What are muscles?
Muscle cells (muscle fibers) are different from other cells because they can contract when stimulated (usually by a neuron).
Put muscle fibers together in an orderly array and they form a muscle capable of developing strong forces.
Skeletal muscle fibers are the effectors of the somatic nervous system and smooth muscle is the common effector of the autonomic nervous system.

As the effectors of the somatic nervous system that controls skeletal movement muscles are arranged in antagonistic pairs.
Relaxation of an effector muscle does not allow the body to return to a previous position.
Antagonous contraction and relaxation by opposing muscles also stops appendages flopping about!

Review of skeletal muscle structure
Starting from the outside:
Muscles are surrounded by connective tissue called the fascia and epimysium which is continuous with tendons that connect muscles to bones.
Tendons contain lots of the protein collagen, giving tensile strength.
Muscle is divided internally by connective tissue called perimysium into groups called fasiculi or fasicles (sing. fasciculus or fasicle).

Within each fasicle connective tissue called endomysium surrounds each each muscle cell (muscle fiber) and connect them to each other.
All the connective tissue layers are continuous allowing the contractile force of muscles to act effectively at the site of insertion.

Muscle fibers (cells) have the same organelles as other cells with some modification.
They generally contain many mitochondria.
Because muscle cells use a lot of energy. They need to convert a lot of glucoseor other fuels to ATP.
They are multinucleated!
They contain special organelles called myofibrils that can contract!

So how does a muscle fiber contract?
The myofibrils (organelles) are packed full of myofilaments which are filamentous proteins.
There are 2 myofilaments:
thick filaments made of myosin
thin filaments
made largely of actin
The myofibrils are also divided into sections called sarcomeres.
The sarcomeres are the units of contraction.
In skeletal muscle these can be distinguished by the striations.

The "big picture" explanation of muscle contraction is that thin filaments are pulled over the thick filaments (sliding filament theory).
The special arrangement of filaments, actin at each end, and myosin in the middle, shorten the sarcomere when actin moves over myosin.

Actin filaments are connected to the z-plates which form the ends of the sarcomeres.
Muscle contraction involves a simultaneous contraction of all the sarcomeres in a cell resulting in shortening of the muscle cell.

The molecular basis for contraction
How do the filaments slide over each other?
Thick filaments contain many molecules (100s) of the protein myosin. Each molecule has a filamentous section and 2 globular heads that protrude from the filament. The myosin heads are referred to as crossbridges.

Each globular head has an ATP binding site and act as a myosin ATP-ase enzyme.
ATP-ase splits ATP into ADP and P plus ENERGY. Some of the energy changes the shape of the myosin head and is involved in shortening of the sarcomeres. Some of the energy is lost as heat.

Myosin heads also have a site that can bind to actin.
When myosin binds to actin, Pi is forced of the myosin head. The loss of Pi induces a shape change in myosin and the head moves toward the center of the cell pulling the actin filament.

In this new position ATP has higher affinity to the myosin than ADP, ADP is pushed off the myosin and the bond with actin is broken.

Myosin bonds with a new ATP (with magnesium, Mg2+) and splits it into ADP and Pi. The split changes the myosin back to its initial shape and the cycle starts again.

What would happen if no ATP is available?
Bonds would not be broken.
What circumstances would lead to no ATP being available?
Rigor mortis is the condition of stiff muscles after death.

So how is contraction controlled?
Muscle relaxation takes place when the bond between actin and myosin is prevented from forming.
The thin filaments are composed of more than just actin.
They are composed of 3 proteins actin, tropomyosin and troponin.
In a relaxed muscle the tropomyosin molecule wraps around actin and blocks the myosin binding site.
Troponin is attached to actin and tropomyosin.

When a muscle is stimulated to contract, Ca2+ is released from the sarcoplasmic reticulum, binds to troponin which moves and pulls tropomyosin off the myosin binding site, allowing myosin to bind to actin.
Muscle contraction continues while Ca2+ and ATP are present.

Smooth Muscle
There are no sarcomeres present in smooth muscles.
Instead, actin is attached to a regular array of dense bodies distributed throughout the cell. Dense bodies are noncontractile protein filaments attached to the cell membrane (sarcolemma). Equivalent to z plates.
Actin and myosin myofibrils are not parallel to the long axis of the cell but diagonal.


There is no troponin associated with actin in smooth muscle.
Filament sliding similar to striated muscle but cross bridging mechanism slightly different.
Ca2+ triggers contraction by different mechanism.
Ca2+, from SR but mainly from outside thecell, causes (via calmodulin and a myosin kinase) phosphorylation (using ATP) of the myosin head to the energized state and crossbridge cycling.

Smooth muscle contraction is slow, sustained and resists fatigue.
It is about 30 X slower to contract than skeletal muscle.
It maintains contraction using very little energy and it is thought that some of the crossbridges lock to actin.
Smooth muscle can be stretched to 2.5 x resting length and still contract efficiently.

Cardiac muscle are striated muscles and have sarcomeres like skeletal muscle.

Neural control of skeletal muscle
Skeletal muscle cell contraction is controlled by the efferent somatic neurons called alpha motor neurons.
Every skeletal muscle cell has a neuromuscular connection.
One alpha motor neuron may contact more than one muscle cell.
A motor neuron and the muscle cells it contacts is called a motor unit.
Different motor units have different numbers of muscle cells.

Motor unit recruitment is used to regulate muscle contraction.
Depending on the neurons that are stimulated various numbers of muscle cells are stimulated to contract.
Fine movements might have many motor units with few muscle cells each etc.
Alternating recruitment of motor units prevents muscle fatigue e.g. walking.
What stimulates a muscle fiber to contract?
Muscle fibers are excitable cells as are neurons. Resting potential in muscle fibers are maintained in much the same way as in neurons.
Contraction of a muscle fibers follows an action potential in the sarcolemma.
Contraction events are stimulated by motor neurons and in some cases in smooth muscle by hormones.

Neuromuscular junction
In a skeletal neuromuscular junction, an AP in the motor neuron results in release of neurotransmitter ACh.
ACh receptors bind ACh in the muscle cell and a local depolarization event occurs which is always sufficient to reach threshold.
One to one relationship.
An AP in a motor neuron results in contraction of a muscle fiber.

Neuromuscular connections are not as close and neurotransmitter spreads over a larger area, often contacting more than one muscle fiber.
Smooth muscle fibers and cardiac muscle fibers may be connected to each other by gap junctions.
This allow a contraction event to spread from one muscle cell to another and not every cell has neuronal connections.
How does an AP result in contraction?
The AP spreads across the sarcolemma and down transverse or T tubules in the muscle fiber.
The depolarization of the membrane in the T tubules results in opening of Ca2+ channels in the sarcoplasmic reticulum for a short period and the release of Ca2+ into the cytoplasm (myoplasm). T Tubule membranes and the sarcoplasmic reticulum are physically linked by DHP (dihydropyridine) receptors in T tubules to protein channels called foot structures (or ryanodine receptors) in the SR.
Ca2+ binds to troponin and cross bridges bind to actin.

Ca2+ is actively pumped back into the sarcoplasmic reticulum reducing cytoplasmic concentrations.
With Ca2+ concentration drops, Ca2+ dissociates from troponin and muscle relaxes.

Smooth muscle fibers and cardiac muscle fibers may be connected to each other by gap junctions.
This allow a contraction event to spread from one muscle cell to another and not every cell has neuronal connections.
Neuromuscular connections are not as close and neurotransmitter spreads over a larger area, often contacting more than one muscle fiber.

A single contraction event is called a muscle twitch.
Force of contraction is a result of temporal summation of twitch force, i.e. results from frequency of APs.
Force of muscle contraction can be graded or varied depending on AP frequency
A sustained contraction with no intermediate relaxation is called tetanus.

The force of a muscle contraction is influenced by the length of the muscle (the amount of muscle stretch).
There is an ideal resting length where force of contraction is greatest (100-120% of rest length).
As a muscle is stretched there is less overlap of the actin and myosin.
As a muscle shortens to about 60% of resting length, the myosin hits the z lines and can't get any shorter.

Control of muscle contraction is a constant process. Sensory feedback is necessary for the nervous system to pick up position of a limb and strength of contraction needed (tension).
Sensory information on muscle length in provided by the muscle spindle.
It consists of special muscle cells called infrafusal fibers (IFFs) located within a connective tissue sheath within normal skeletal muscle (extrafusal) tissue.

Intrafusal muscle fibers (IFFs) are modified - there are no sarcomeres in the center part of the cells which is elastic.
2 types of sensory neurons are attached to the IFFs which are stretch receptors. These pick up onset of stretching and sustained stretch.
Gamma motor neurons stimulate IFFs to contract.

In normal muscle contraction both alpha and gamma motor nuerons stimulate EFFs and IFFs to contract. The muscle spindle apparatus provides spatial information to the CNS as to where the muscle (and limb) are located.
A sudden stretch of the muscle (and IFFS) results in a contraction the EFFs. Stretch receptors in the spindle apparatus synapse with alpha motor neurons. This explains the knee jerk reflex - a simple reflex arc.
This tests function of the CNS.

A second sensory receptor of muscle activity are golgi tendon organs. Located within tendons they continually monitor tension.
Strangely enough as tension increases their stimulation has an inhibitory effect on alpha motor neurons.
They are are thought to protect a muscle from over stretching or tearing.

Note: stretching stimulates golgi tendon organs and spindle apparatus sensory neurons which each have opposing effects on alpha motor neurons.

Skeletal muscle is arranged so that there is reciprocal innervation of antagonistic muscles.
Interneurons within the CNS make these connections.
When an extensor muscle contracts, flexor muscles are inhibited and stretch.
Sensory feedback from spindle apparatus keeps correct tension in each muscle.

ATP is essential to supply the energy for muscle contraction.
Three pathways are used for ATP production in skeletal muscle.

1. Oxidative phosphorylation of ADP in mitochondria using glucose or fatty acids as the source of the acetyl CoA in the Krebs cycle.
2. Glycolysis and anaerobic lactate fermentation. Much less ATP provided but no oxygen necessary.
3. Creatine phosphate supplies ATP during short burst of extreme muscle activity.

creatine phosphate +ADP -> creatine +ATP
Facilitated by enzyme, creatine kinase.

Muscle cells draw on different sources of energy during exercise.
During low levels of exercise, lipids are the primary source but during heavy exercise stores of muscle glycogen are used.
Some athletes vary their diet to build up more glycogen in their muscle cells.

Three types of skeletal muscle based on ATP synthesis pathway
1. Slow oxidative (slow twitch), type I fibers
2. Fast oxidative (fast twitch), type IIa fibers
3. Fast glycolytic (fast twitch), type IIb fibers



Type I

Type IIa

 Type IIb
 myosin ATPase activity



 speed of contraction



 resistance to fatigue



 oxidative phosphylation capacity



 anaerobic pathway enzymes



 mitochondria number



 blood supply



 myoglobin concentration



 glycogen content



 fiber diameter



 force of contraction







Training often has 2 aims - increase strength and increase indurance.
Putting tension strain on muscles (e.g. weight training) causes more myofibrils to be produced in each muscle fiber. Cell numbers do not increase.
Aerobic training increases mitochondria and myoglobin in cells and the cells ability to produce ATP aerobically.


Clinical question.

What are the affects on the muscular system arising from infection by the two different bacteria Clostridium tetani and Clostridium botulinum?

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This webpage was created by Peter King. Please contact the the author with comments at
Last edited July 20, 2010.
copyright Peter King.