Unit X - Muscle

Muscle is the excitable tissue in which the secondary response is contraction or shortening. The contraction of muscle almost always results in some type of movement by the body. In this unit the structure and functioning of muscle will be examined.

A. Muscle types and functions - There are three types of muscle found in the body. Each type differs in both its structure and function. These three types are as follows.

1. Skeletal (striated, voluntary) muscle - This is the muscle which is attached to the skeleton. It is the most abundant of the three types of muscle. It functions in movement and the maintenance of position. Each muscle cell is very large with prominent cross markings or striations. The cells are multinucleated and each cell is innervated by a nerve fiber from the voluntary (somatic) division of the nervous system. For this reason skeletal muscle is under conscious control and is therefore sometimes referred to as voluntary muscle.

2. Smooth (involuntary) muscle - This muscle type is found in the walls of the hollow organs where it normally functions to control the movement of materials through these organs. The cells are much smaller than those of skeletal muscle and are spindle (pointed at both ends) shaped. Each cell is uninucleate. The cells are not striated and thus have a smooth appearance. Innervation is frequently not present except to entire masses, and it is then derived from the involuntary (autonomic) division of the nervous system. For that reason, smooth muscle is not under conscious control.

3. Cardiac muscle - This is the muscle of the heart. The cells are branching and separated from one another by intercalated disks which give cardiac muscle special properties. There is not individual innervation to each cell, but there is innervation to the entire cardiac mass. This innervation is derived from the autonomic division of the nervous system and as a consequence, cardiac muscle, like smooth muscle, is not under conscious control. The details of cardiac muscle will be discussed later with the circulatory system.

B. Skeletal muscle - This is not only the most abundant muscle in the body, but it is also the type about which most is known. For this reason it will be discussed in greater detail than the other types of muscle.

1. Gross anatomy - A typical skeletal muscle is a complex organ which contains connective and nervous tissues in addition the muscle tissue. Although skeletal muscles exhibit many different shapes, a representative muscle might have an enlarged belly which narrows into tendons at either end. The tendons connect the muscle to the bone. A cross section through the belly of this muscle would show the following structures.

a. Epimysium - This is a connective tissue envelope which surrounds the muscle. It becomes confluent with the tendons. The epimysium is part of the deep fascia.

b. Perimysium - This is connective tissue within the muscle that surrounds the fasciculi. Each fasciculus is a bundle of muscle cells.

c. Endomysium - This is connective tissue found within each fasciculus. The endomysium surrounds each individual muscle cell and insulates it from the adjacent cells. This is why each muscle cell must have its own nerve fiber. The insulation of the endomysium means that an action potential cannot move from one cell to another. Satelite cells which permit the repair of damaged muscle, are scattered between the muscle cell and the endomysium.

d. The connective tissues of the skeletal muscle function in the following ways.

(l) They support the nerves and blood vessels that run into and throughout the muscle.

(2) They serve to uniform the pull of the muscle cells during contraction.

(3) They insulate the muscle cells from each other.

2. Histology (microscopic structure) of skeletal muscle

a. Terminology - Muscle has a set of unique terms to describe certain structures. The major terms are defined below.

(l) Fiber or muscle fiber - A muscle cell.

(2) Sarcolemma - The cell membrane of the muscle cell.

(3) Sarcoplasmic reticulum - The highly organized endoplasmic reticulum of a muscle cell.

b. Microscopic examination of a skeletal muscle fiber will show that it is packed with long rod-like structures known as myofibrils. These myofibrils appear to consist of alternating light and dark bands. In the intact muscle cell, the myofibrils lie adjacent in such a way that all of the dark bands are aligned and this is what gives the cell its striated appearance.

c. Further magnification of a single myofibril shows that it is composed of repeating subunits called sarcomeres.

d. Each sarcomere consists of two Z lines (discs), two I bands (light), and one A band (dark). Each A band has a slightly lighter center known as the H zone, and in the center of the H zone is the M line.

e. Still further magnification shows that each sarcomere is composed of thin structures known as myofilaments.

f. There are three types of myofilaments, thin filaments, composed of the proteins actin, troponin, and tropomyosin, thick filaments, composed of the protein myosin, and elastic filaments composed of the protein titin.

g. Analysis of the banded appearance of the sarcomere with regards to the myofilaments shows the following structural plan.

(l) Z lines (discs) are composed of proteins called connectins, that interconnect and anchor the the thin filaments of adjacent sarcomeres.

(2) I bands are composed of thin filaments which are attached at one end to the Z discs.

(3) A bands are composed of thick filaments and thin filaments overlapping.

(4) The H zone is composed of thick filaments only. No overlap occurs in this area and therefore it is lighter that the remainder of the A band. The M line represents protein connections between the

middle of all of the thick filaments. This stabilizes the position of the thick filaments.

(5) The elastic filaments extend from the z discs to the thick filaments where they enter these filaments

and run to the M line where they attach. The elastic filaments hold the thick filaments in place

and contribute the muscles return to normal length after being stretched.

h. In summary, the muscle fiber is composed of myofibrils which are in turn composed of myofilaments.

3. Sarcoplasmic reticulum

a. This is the highly organized endoplasmic reticulum of the muscle cell and it surrounds the sarcomeres. It is most dense around the thick filaments and is expanded into storage sacs termed cisternae at the zones of overlap between the thick and thin filaments.

b. Each cisternae makes contact with a transverse (T) tubule which is an inward extension of the muscle cell membrane (sarcolemma).

c. The T-tubule is oriented at right angles to the sarcolemma and pass between the myofibrils where they branch to completely encircle the sarcomeres.

4. Neuromuscular (myoneural) junction - Every skeletal muscle cell receives a nerve fiber and that point where the nerve fiber meets the muscle cell is termed the neuromuscular junction.

a. The nerve fiber does not actually touch the muscle sarcolemma. There is a small space between known as the neuromuscular gap. That section of the sarcolemma which lies directly beneath the nerve fiber is termed the motor end plate.

b. The nerve impulse (action potential) moves from the nerve fiber across the gap to the motor end plate which it causes to depolarize. The depolarization wave then spreads from the motor end plate across the remainder of the sarcolemma.

C. The mechanism of muscle contraction - In order for the skeletal muscle cell to contract, it must first be excited, an action potential must move across the membrane. For skeletal muscle the excitation source is always the nervous system. A nerve impulse (action potential) arrives from the nervous system, crosses the neuromuscular junction, and causes depolarization of the motor end plate.

1. Mechanism of impulse transmission across the neuromuscular junction - excitation

a. The action potential reaches the terminal end of the nerve fiber where it causes the rupture of small vesicles in the nerve cell.

b. These vesicles release a chemical called acetylcholine which diffuses across the neuromuscular gap and attaches to receptors on the motor end plate of the sarcolemma.

c. Acetylcholine attaches to receptors on the motor end plate of the sarcolemma. This attachment open the chemically controlled sodium channels which result in the inward movement of sodium and the development of local potentials known as miniature end plate potentials (EPP). Once the EPP is large enough to reach threshold, the electrically controlled sodium channels open and sodium floods inward initiating an action potential. Normally every EPP reaches threshold and therefore each nerve impulse yields an action potential on the muscle cell membrane.

d. An enzyme located on the motor end plate named acetylcholinesterase immediately breaks down acetylcholine thereby permitting the permeability of the motor end plate to return to normal and repolarization of the sarcolemma to occur.


2. Contraction

a. The action potential moves across the entire sarcolemma, including the transverse tubules. The movement of the action potential deep into the transverse tubules causes the cisternae to release calcium ion which has been stored in them.

b. It is calcium that provides the link between excitation and contraction.

c. The released calcium diffuses into the myofibrils where it interacts with the myofilaments, triggering the contraction process.

d. Contraction involves the sliding inward of the thin filaments between the thick filaments. This pulls the Z discs closer together thereby causing each sarcomere to shorten.

e. The thin filaments slide because they attach to cross bridges found on the myosin thick filaments. These cross bridges pivot, and this results in the pulling of the thin filaments inward.

    1. Calcium interacts with troponin which acts like a switch, changing the shape of the troponin-tropomyosin complex. This uncovers cross bridge binding sites on the thin filaments. The exposed binding sites now lock on to the cross bridges of the thick filaments.
    2. The swiveling of the cross bridges that results in the inward sliding of the filaments is due to the following events.
      1. When the mysosin head of the cross bridge attaches it is in the high-energy configuration. As soon as it attaches to the binding site on actin it returns to its low-energy configuration. In doing so it bends and that causes the thin filament to ratchet inward. This is known as the power stroke.
      2. A new ATP attaches to the myosin head which causes it to detach from the binding site on actin.
      3. The ATP is hydrolyzed to ADP, this releases energy which then returns the myosin head to its high-energy configuration. This is referred to as the "cocking" of the myosin head.
      4. The myosin head now binds to a new binding site the process is repeated. By this constant attaching, swiveling, and detaching, the cross bridges ratchet the thin filaments inward and the sarcomere shortens.

h. Summary - The action potential causes release of calcium from the sarcoplasmic reticulum. The calcium initiates a series of biochemical changes which result in the inward movement of the thin filaments thereby shortening each sarcomere, myofibril, and ultimately the entire muscle cell.

3. Relaxation

a. Termination of the action potential permits the sarcoplasmic reticulum to actively transport calcium out of the myofibrils.

b. The loss of calcium results in reattachment of the troponin-tropomyosin complex to the binding sites and the breaking off of contact with the cross bridges.

c. The end result is that the thin filaments are no longer attached to the thick filaments and slide back to the resting relaxed length. Lenthening is brought about by external forces such as elastic elements in the muscle cell and the action of other muscles.

4. In the absence of calcium contraction will not occur. In the absence of ATP, cross bridges will lock on to the thin filaments but contraction will not occur. This is what happens in rigor mortis following death.

D. Energy for contraction - Contraction is an energy consuming process. A very large amount of energy is utilized by a contracting muscle.

l. The efficiency of contraction is about 40%. This means that of the total amount of energy released by ATP, 40% goes into the movement of the myofilaments. The remaining amount is lost as heat.

2. The immediate source of energy for contraction is always ATP. The demand for energy in an contracting muscle is so high that ATP by itself cannot keep up with demand, in fact, the initial available ATP can only power a muscle for about 4 to 6 seconds. There is a secondary source of energy.

3. This secondary source of energy is creatine phosphate. This is a high energy compound which is synthesized from ATP when the muscle is at rest. During rapid contraction, after all of the ATP has been used up, creatine phosphate can donate its high energy phosphate group to ADP thereby regenerating ATP for use. The combination of stored ATP and creatine phosphate can power a muscle for about 15 seconds.

  1. Ultimately the ATP needed for extended activity must be produced by anaerobic and aerobic respiration. When a muscle is exercised at or near maximum capacity, the contracting force compressed the blood vessels in the muscle thereby limiting the amount of blood and oxygen that is available. Under these conditions, the muscle converts glucose to lactic acid, an anaerobic process. This will provide additional energy up to about one minute.
  2. During light to moderate activity, 95% of ATP is supplied by aerobic respiration. As long as exercise is moderate, aerobic respiration can provide adequate amounts of ATP for hours of activity.


E. Oxygen debt - During peak exercise periods the circulatory system may not be able to supply adequate oxygen supplies to the skeletal muscles. Under these circumstances the muscles will begin to generate ATP by converting pyruvate to lactic acid. This can only continue for a short period of time, and after exercise has ceased the lactic acid must be metabolized. The lactic acid is metabolized in the liver and this metabolism requires oxygen. This means that after exercise has ceased, increased amounts of oxygen must still be consumed in order to pay off the "oxygen debt." Oxygen debt is equivalent to lactic acid accumulation.


F. Physiological properties of skeletal muscle

1. Muscle twitch - This is the response of a single muscle cell to a single stimulus. It consists of a latent period, the time it takes the action potential to sweep over the muscle cell, about 2 msec a contraction period, when the cell is actually shortening, about 20 msec, and a relaxation period, when the muscle cell is lengthening, another 25 msec.

2. Response to repetitive stimuli - Because the contraction period is so much longer that the action potential period, it is possible to give a rapid series of stimuli and produce a rapid series of action potentials. The resulting contraction waves follow each other so closely that the muscle never gets time to relax and hence the contraction wave summate or add up. If the series of action potentials are rapid enough then the muscles goes into a smooth sustained contraction known as tetanus. As the rapid series of impulses and the resulting chemical reactions cause the muscle to warm, the force of contraction becomes greater. Hence summated and tetanus type contractions produce more force than single muscle twitches. In the body, all muscle contractions are smooth and sustained, and therefore are of the tetanus type.

  1. Length-Tension relation - the effect of initial length - The initial resting length of a skeletal muscle effects the maximum force of contraction which can be generated. There is an optimum length for maximum contraction force. If the muscle is shorter or longer than this optimum initial length then the force of contraction decreases.

G. Organization of skeletal muscle - All skeletal cells are organized into motor units.

  1. Motor unit - A motor neuron plus all of the muscle cells which it innervates.

2. When the motor neuron conducts an action potential, all of the muscle cells belonging to that unit receive the action potential and contract with maximum force.

3. Whole skeletal muscles increase their force of contraction by recruiting additional motor units. Once all motor units of a muscle are activated then that muscle cannot exert any further force.

4. Muscles of fine control such as those which direct the eye have many motor units and few muscle cells per unit, perhaps 10 to 15. Gross postural muscles may have as many as 800 muscle fibers per motor unit. An average figure would be about 150 per unit.

H. Types of skeletal muscle contraction - There are two basic types of contraction which occur in the body.

1. Isotonic - A muscle develops tension and shortens. These types of contraction are usually associated with movement.

2. Isometric - A muscle develops tension but does not shorten. Usually associated with maintenance of position.

I. Types of muscle fibers - Based upon their speed of contraction and color, three classes of muscle fibers can be recognized in skeletal muscles. All muscles contain all three types, but certain types may predominate in particular muscles. Each motor unit contains only one type of fiber. The three fiber types are as follows.

1. Fast glycolytic fibers - These fibers have a fast rate of contraction (.01 seconds) and lack myoglobin. They are rich in glycogen and depend upon anaerobic glycolysis for energy. Most of the fibers in the typical body are of this type. The rate of fatigue is very rapid.

2. Slow oxidative fibers - These fibers are characterized by a slow rate of contraction (three times slower than fast) the red oxygen carrying pigment myoglobin. They are about half the diameter of the fast fibers. They rely primarily on oxidative generation of ATP for energy. They have an low rate of fatigue.

2. Fast oxidative fibers - These fibers are intermediate between fast and slow. They are large like fast fibers and are pale due to low amounts of myoglobin. They have a more extensive capillary network supplying them than do the fast fibers and are therefore slower to fatigue.

J. Muscle fatigue - This is a general weakness of heavily exercised muscle which seems to be primarily due to a loss of energy reserves. This results in a depletion of ATP. Accumulation of lactic acid may also contribute.

K. Effects of activity - A certain amount of activity is essential for the well being of skeletal muscle. A muscle which is exercised regularly and with vigor will undergo certain adaptive changes depending upon the type of exercise.

1. Isometric exercise - Here the muscle is placed under tension but not much movement occurs. Weight lifting is an isometric type of exercise. Muscle responds to this type of exercise by hypertrophying, increasing in size and strength. This is due to an increase in the number of myofibrils in each cell. Although these muscles get stronger they do not increase in endurance.

2. Isotonic exercise - Muscles are exercised vigorously over extended periods of time with a great amount of movement. This is aerobic types of exercise and includes such things as jogging, swimming, tennis, hand ball, etc. Muscles respond to this type of exercise by increasing their endurance, largely due to increased aerobic energy generating capacity. All three types of fibers become more aerobic: they increase their ability to extract and utilize oxygen. There is no increase in size or strength. Aerobic type exercise also enhances the efficiency of the circulatory system.


L. General aspects of skeletal muscles as whole organs

1. Skeletal muscles are complex organs composed of muscle, nervous, and connective tissues. Each is connected to the nervous system and has an extensive circulation. They constitute 35% of the body weight in women and 40% in men. There are over 600 muscles in the body.

2. Attachment to the skeleton

a. Direct attachment - Here the connective tissue envelope of the muscle is fused directly to the periosteum of the bone.

b Connective by tendons - These are bundles of dense connective tissue which is continuous with the envelope surrounding the muscle. They may be rope-like or sheet-like. Sheet-like tendons are termed aponeuroses.

3. Origin and insertion - Most skeletal muscles have an origin and insertions on the skeleton. The origin is the attachment point which shows the least movement and the insertion is the attachment point that shows the most movement.

4. Action of muscles

a. Muscles can exert their effect by pulling only, usually across joints.

b. As muscles can only pull across joints it follows that there must be a muscle or set of muscles for every movement a joint is capable of performing. This is accomplished by arranging muscles into antagonistic groups. If there is a muscle or a groups muscles which move a joint in one direction, there will be an antagonistic set which move it (pull) in the opposite direction.

c. A good example of antagonistic muscles are the biceps brachii which flexes the forearm and the triceps which extends the forearm.

d. Within each group of muscles there is usually one which is primarily responsible for the group action. It is termed the primer mover. The other muscles which aid the prime mover are known as synergists.

5. Muscle nomenclature - Skeletal muscles are named by about 7 different methods.

a. Action - flexor digitorum (flexes the digits)

b. Location - tibialis anterior (anterior surface of the tibia)

c. Number of heads of origin - triceps (three heads)

d. Shape - deltoid (delta or triangular shaped)

e. Origin and insertion - sternocleidomastoid (attached to the sternum, clavicle, and mastoid process)

f. Size - gluteus maximus (the large gluteal muscle)

    1. Direction of muscle fibers - rectus (straight fibers, parallel to midline of body), oblique (fibers run at

an angle to the midline of the body), transverse (fibers run at 90 degrees to midline of body).

M. Selected pathologies

1. Myasthenia gravis - This is a weakness of skeletal muscle. There is a loss of acetylcholine receptor sites on the motor end plates due to autoimmune disease. The result is that the cells do not contract as often as they should. It can be treated with anticholinesterase drugs and with immunosuppressants.

2. Muscular dystrophy - This is characterized by degeneration of the muscle cells. The muscles are usually replaced by fat. There are two forms, both hereditary. One effects only males (Duchenne) and appears in early childhood. By adolescence the individual is usually in a wheel chair. The other form effects both sexes and appears later in life. Duchenne muscular dystrophy is due to the absence of a protein known as dystrophin which is normally found in the muscle fiber. It functions to support the sarcolemma internally. There is no known cure although injection of myoblasts (embryonic muscle cells) into diseased cells is being tested experimentally. The embryonic cells frequently fuse with the diseased cells and restore the ability to produce dystrophin.

3. Cramps - This is a painful spasmodic contraction of muscle. It is an involuntary complete tetanic contraction. The cause is not known but they often appear when an individual has exercise the muscles at a very high level of intensity.

N. Effects of aging - Beginning in the middle twenties there is a continuous and progressive loss of skeletal muscle cells. These are usually replaced by fat. This results in a decrease in maximum strength which declines about 50% between the ages of 20 and 80.

O. Smooth muscle - These cells are much smaller than skeletal muscle cells, uninucleate, and lack striations. They have a high capacity for anaerobic metabolism.

1. Structure - All though the overall metabolism of smooth muscle is similar to that of skeletal, the organization is quite different.

a. Smooth muscle contains thick filaments of myosin, smaller filaments known as myosin light chains, intermediate filaments(found in all cells), and thin filaments composed of actin and tropomyosin. Note that there is no troponin. These filaments are not organized into sarcomeres (therefore, no striations) but appear to slide in the same manner as skeletal muscle.

b. The intermediate filaments are connected to structures known as dense bodies. These are found throughout the sarcoplasm and attached to the sarcolemma. They seem to function the same as the Z discs.

c. The sarcoplasmic reticulum is much less organized than the equivalent structure in skeletal muscle.

2. Contraction

a. Calcium moves into the cell following an action potential. The source of this calcium is both the sarcoplasmic reticulum (as in skeletal muscle) and the extracellular fluid, across the sarcolemma.

b. The calcium binds with an intracellular protein known as calmodulin which then activates an enzyme known as myosin light chain kinase. This causes phosphate groups to be transferred to the myosin light chains which in turn activate the interaction of the thick and thin filaments which then slide.

c. The thin filaments are attached to the intermediate filaments and pull upon them causing the dense bodies to be pulled toward one another. This cause the cell to contract.

d. Relaxation occurs when the calcium has been pumped out of the sarcoplasm, either into the sarcoplasmic reticulum or across the sarcolemma into the extracellular fluid. The loss of calcium inactivate myosin light chain kinase and a second enzyme known as myosin light chain phosphatase causes the removal of the phosphate groups from the myosin light chains which permit the thin and thick filaments to slide apart.

3. Classes of smooth muscle

a. Multi-unit - This behaves very much like skeletal muscle. It requires innervation but innervation comes from the autonomic nervous division. It will exhibit summation and tetanus and is organized into motor units. Gap junctions are lacking. It is found in the ciliary body and iris of the eye as well as in the walls of the blood vessels, and the arrector pili muscles of the hair follicles.

b. Single unit (unitary or visceral) - This does not require innervation for contraction (but it may be innervated). It does not exhibit summation or tetanus. It is found in the walls of the hollow internal organs such as the digestive, urinary, respiratory and reproductive tracts.

(l) Characteristics of unitary smooth muscle

(a) It responds as a unit. When one cell in a mass depolarizes it causes all of the other cells surround it to depolarize.

(b) Ephatic conduction - This is the excitation of a cell membrane due to its coming into contact with another cell membrane which is excited. Unitary smooth muscle cells are connected by gap junctions and this makes ephatic conduction possible. This is why unitary smooth muscle responds as a unit.

(c) Pacemaker cells - Unitary smooth muscle contains cells that depolarize spontaneously. Once a cell has depolarized the depolarization wave will spread over the entire mass by ephatic conduction. Pacemaker cells will determine the contraction rate for unitary smooth muscle.

(d) The rate of pacemaker cell activity can be influenced by a number of factors. These include chemical substances released by nerve cells (neurotransmitters), hormones, and physical factors such as stretching.

(e) Plasticity (Stress-relaxation response) - Unitary muscle can be stretched without changing its force of contraction. Therefore its force of contraction does not change with resting length as does skeletal and cardiac muscle. It is this plasticity that makes it possible to greatly distend the hollow organs such as the stomach and urinary bladder and still maintain adequate tension.

4. Compared to skeletal muscle smooth muscle in general shows a slower contraction and relaxation rates but has the ability to remain in the contracted state for extended periods of time. This is important for the proper functioning of the internal organs.

5. Hyperplasia - Certain smooth muscle cells are capable of dividing and thereby increasing their numbers. A good example is the increase in numbers of smooth muscle cells in the female uterus at puberty.