This web page contains notes to accompany lectures in Vertebrate Physiology, Biology 410, taught by Dr. Peter King in the Department of Biology, Francis Marion University, Florence, South Carolina, 29502, USA.

The effectors of the nervous sytem are almost all muscle cells.
Muscles are all excitable cells but are divided into 3 types:
1. skeletal muscle
2. smooth muscle
3. cardiac muscle

Muscle cells are excitable cells that contract when stimulated.
Skeletal muscle (striated muscle) is enervated by somatic motor neurons that are generally under voluntary control.
Skeletal muscles are attached to the skeleton and are responsible for its movement.

Smooth muscle is enervated by the autonomic nervous system and is not under voluntary control.
Smooth muscles are found in visceral organs e.g. stomach, intestine, glands, blood vessels etc.

Cardiac muscle is the heart muscle. It has intermediate properties between sooth and striated muscle.

Most information about the mechanism of contraction comes from skeletal muscle.
Skeletal muscle (striated muscle)
A muscle cell is called a muscle fiber.
Skeletal muscle cells are long thin cells, 5-100 mm wide and can be several cm long.

Within skeletal muscle the proteins that take part in the contraction process are aligned such that they form visual striations.
Each muscle cell is packed full of special organelles call myofibrils that run the length of the cell.
The myofibrils are divided into units of contraction called sarcomeres.

How does a sarcomere contract?
The ends of the cylindrical sarcomere are proteinaceous Z lines.
Attached to the Z line and extending in both directions are thin myofilaments made largely of the protein actin.
Between the thin myofilaments are many thick myofilaments made of the protein myosin, which is positioned in the center of the sarcomere between the Z lines.

Sliding Filament Theory
Contraction takes place when actin slides over myosin pulling the two Z lines toward the center of the sarcomere.

Lets look at the molecular structure
Thin myofilaments
The main structural element of the thin filament are actin molecules that join together into two twisting strands.
Each actin molecule has a special binding site that can attach to myosin.
Around each strand of actin winds another threadlike protein tropomyosin.
At rest tropomyosin covers the myosin binding site.
A single thin myofilament has about 400 actin molecules and 60 tropomyosin molecules.
A third small globular protein troponin helps secure tropomyosin to the actin.

Thick myofilaments
Each thick filament is made up of several hundred molecules of the protein myosin.
Each molecule has two subunits shaped something like hockey sticks, with the globular heads separated by the two long protein tails (hockey stick handles).

The protein tails of adjacent molecules bind together and the heads project from the body of the thick filament.
On the head of each myosin molecule is a binding site for actin and an ATPase site.

Molecular basis of contraction
The process that causes the actin to slide over myosin is called cross bridging.
1. ATP (with magnesium, Mg²⁺) attaches to myosin head in a relaxed position.
2. Myosin ATPase dephosphorylates ATP and absorbs energy - changes shape to an energized position. It can remain in this position at rest.
3. Calcium (Ca²⁺) released on stimulation, binds to troponin which causes a conformational change that shifts tropomyosin away from the myosin binding site.
4. Myosin head binds to actin (forms cross bridge).
5. When the cross bridge forms, Pi is pushed of the myosin head causing a change in shape back to the relaxed position. ADP is released at the end of the power stroke.
6. Change in position pulls the actin filament toward the center of the sarcomere.
7. ATP (with magnesium, Mg²⁺) attaches to the ATPase site causing cross bridge of actin and myosin to break.

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⁺ causes (via calmodulin and a kinase) phosphorylation (using ATP) of the myosin head to the energized state and cross bridge formation.

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 cross bridges lock together.
Most ATP is delivered via anaerobic pathways.

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

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).
Ca²⁺ binds to troponin and cross bridges can form.
Ca²⁺ is actively pumped back into the sarcoplasmic reticulum reducing cytoplasmic concentrations.
With Ca²⁺ concentration drops, Ca²⁺ dissociates from troponin and muscle relaxes.

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.
A sustained contraction with no intermediate relaxation is called tetanus.

Muscle recruitment
Skeletal muscle fibers are electrically insulated from each other in a muscle and each muscle fiber has one neuromuscular junction.
A motor neuron and the muscle fibers it contacts is called a motor unit.
Motor units vary in the numbers of muscle fibers they contain.
Control of skeletal muscle contraction depends on the motor units employed.
During prolong sustained delivery of force, asynchronous recruitment of motor units takes place.
Muscle recruitment also allows the neural control of fine and gross movements.

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.

ATP essential to supply the energy for 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.

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

Characteristics

Muscle length effects the force delivered in a contraction.
Optimal muscle length is usually its resting length allows maximum number of cross bridges to form.
Stretched muscle has some myosin heads too far from the actin myofilament
Contacted muscle can have overlapping thin filament which prevents movement.

Return to Index

This page was created by Peter King. Please contact the author at pking@fmarion.edu with comments.
http://people.fmarion.edu/pking/vertphys/muscles.html
Last edit January 10, 2011.
Copyright Peter King.