BIOL 237

Class Notes

The Muscular System

 

Muscular Histology & Structure

There are three types of muscle tissue, all of which share some common properties: excitability or responsiveness - muscle tissue can be stimulated by electrical, physical, or chemical means. contractility - the response of muscle tissue to stimulation is contraction, or shortening. elasticity or recoil - muscles have elastic elements (later we will call these their series elastic elements) which cause them to recoil to their original size. stretchability or extensibility - muscles can also stretch and extend to a longer-than-resting length.

The three types of muscle: skeletal, cardiac, and visceral (smooth) muscle. [See Muscle Histology] You should make a chart similar to Table 9.4 and the one from class. Skeletal muscle is found attached to the bones for movement. Its cells are long multi-nucleated cylinders. They acquired this characteristic because they develop from the fusion of small single cells into long units. The cells may be many inches long but vary in diameter, averaging between 100 and 150 microns. Skeletal muscle cells are independent cells separated from one another by connective tissue and must each be stimulated by axons of a neuron. All the cells innervated by branches from the same neuron will contract at the same time and are referred to as a motor unit. Motor units vary in size: large motor units with more than 100 cells are typical of the slow acting postural muscles. Very small motor units with around 10 cells or so are typical of fast acting muscles with very precise control such as those which move the eye. Most of our muscles have a mixture of motor units of different sizes. Skeletal muscle is voluntary because the neurons which innervate it come from the somatic or voluntary branch of the nervous system. That means you have willful control over your skeletal muscles. Skeletal muscles have distinct stripes or striations which identify them and are related to the organization of protein myofilaments inside the cell. NOTE: Skeletal muscle cells are associated with a type of stem cell known as a satellite cell. These cells are believed to aid in recovery of muscle fibers from damage and can contribute their nuclei to replace and supplement the nuclei of the damaged cells. This occurs in response to the "microtears" produced by strenuous exercise and results in increased production of proteins and myofibrils. IGF-1 (Insulin Growth Factor) is released locally as a result of exercise and is believed to play a major role in attracting the satellite cells to the site of the injury.

Cardiac muscle is the muscle found in the heart. It is composed of much shorter cells than skeletal muscle which branch to connect to one another. These connections are by means of gap junctions called intercalated disks which allow an electrochemical impulse to pass to all the connected cells. This causes the cells to form a functional network called a syncytium in which the cells work as a unit. Faint striations indicate a similar, but not identical, arrangement of myofilaments in cardiac and skeletal muscle. Many cardiac muscle cells are myogenic which means that the impulse arises from the muscle, not from the nervous system. This causes the heart muscle and the heart itself to beat with its own natural rhythm. But the autonomic nervous system controls the rate of the heart and allows it to respond to stress and other demands. As such the heart is said to be involuntary.

Visceral muscle is found in the body's internal organs and blood vessels. It is usually called smooth muscle because it has no striations and is therefore smooth in appearance. It is found as layers in the mucous membranes of the respiratory and digestive systems. It is found as distinct bands in the walls of blood vessels and as sphincter muscles. Single unit smooth muscle is also connected into a syncytium similar to cardiac muscle and is also partly myogenic. As such it causes continual rhythmic contractions in the stomach and intestine. There and in blood vessels smooth muscle also forms multiunit muscle which is stimulated by the autonomic nervous system. So smooth muscle is involuntary as well. See also Figure 9.21 (modified).

Structure and function of skeletal muscle. Skeletal muscles have a belly which contains the cells and which attaches by means of tendons or aponeuroses to a bone or other tissue. An aponeurosis is a broad, flat, tendinous attachment, usually along the edge of a muscle. A muscle attaches to an origin and an insertion. The origin is the more fixed attachment, the insertion is the more movable attachment. A muscle acts to shorten, pulling the insertion toward the origin. A muscle can only pull, it cannot push. Muscles usually come in pairs of antagonistic muscles. The muscle performing the prime movement is the agonist, the opposite acting muscle is the antagonist. When the movement reverses, the names reverse. For example, in flexing the elbow the biceps brachii is the agonist, the triceps brachii is the antagonist. When the movement changes to extension of the elbow, the triceps becomes the agonist and the biceps the antagonist. An antagonist is never totally relaxed. Its function is to provide control and damping of movement by maintaining tone against the agonist. This is called eccentric movement. Muscles can also act as synergists, working together to perform a movement. This movement can be different from that performed when the muscles work independently. For example, the sternocleidomastoid muscles each rotate the head in a different direction. But as synergists they flex the neck. Fixators act to keep a part from moving. For example fixators act as postural muscles to keep the spine erect and the leg and vertebral column extended when standing. Fixators such as the rhomboids and levator scapulae keep the scapula from moving during actions such as lifting with the arms. Your assignment is to make a chart of the muscles showing their location and action. Look for examples of antagonists, synergists, and fixators. You may find the Muscle Action Page helpful in identifying these characteristics.

 

Muscle Cell Structure and Physiology

The functional characteristics of a skeletal muscle cell: The cell membrane is called the sarcolemma. This membrane is structured to receive and conduct stimuli. The sarcoplasm of the cell is filled with contractile myofibrils and this results in the nuclei and other organelles being relegated to the edge of the cell. Myofibrils are contractile units within the cell which consist of a regular array of protein myofilaments. Each myofilament runs longitudinally with respect to the muscle fiber. There are two types: the thick bands and the thin bands. Thick bands are made of multiple molecules of a protein called myosin. The thin bands are made of multiple molecules of a protein called actin. The thin actin bands are attached to a Z-line or Z-disk of an elastic protein called titin. The titin protein also extends into the myofibril anchoring the other bands in position. From each Z-line to the next is a unit called the       The sarcomere is the smallest contractile unit in the myofibril. Sarcomeres contract because the Z-lines move closer together. As the sarcomeres contract the myofibrils contract. As the myofibrils contract the muscle cell contracts. And as the cells contract the entire muscle contracts. The arrangement of the thick myosin filaments across the myofibrils and the cell causes them to refract light and produce a dark band known as the A Band. In between the A bands is a light area where there are no thick myofilaments, only thin actin filaments. These are called the I Bands. The dark bands are the striations seen with the light microscope.

The Sliding Filament mechanism of muscle contraction. When a muscle contracts the light I bands disappear and the dark A bands move closer together. This is due to the sliding of the actin and myosin myofilaments against one another. The Z-lines pull together and the sarcomere shortens as above. The thick myosin bands are not single myosin proteins but are made of multiple myosin molecules. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick bands as shown in Figure 9.3 a and b, modified. It is the myosin heads which form crossbridges that attach to binding sites on the actin molecules and then swivel to bring the Z-lines together. Likewise the thin bands are not single actin molecules. Actin is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) which produces the thin filament. Each thin myofilament is wrapped by a tropomyosin protein, which in turn is connected to the troponin complex. (See Figures 9.3 c and 9.7). The tropomyosin-troponin combination blocks the active sites on the actin molecules preventing crossbridge formation. The troponin complex consists of three components: TnT, the part which attaches to tropomyosin, TnI, an inhibitory portion which attaches to actin, and TnC which binds calcium ions. When excess calcium ions are released they bind to the TnC causing the troponin-tropomyosin complex to move, releasing the blockage on the active sites. As soon as this happens the myosin heads bind to these active sites.

Events in Muscle Contraction - the sequence of events in crossbridge formation: (See Figure 9.8, modified at left) 1) In response to Ca+2 release into the sarcoplasm, the troponin-tropomyosin complex removes its block from actin, and the myosin heads immediately bind to active sites. 2) The myosin heads then swivel, the Working Stroke, pulling the Z-lines closer together and shortening the sarcomeres. As this occurs the products of ATP hydrolysis, ADP and Pi, are released. 3) ATP is taken up by the myosin heads as the crossbridges detach. If ATP is unavailable at this point the crossbridges cannot detach and release. Such a condition occurs in rigor mortis, the tensing seen in muscles after death, and in extreme forms of contracture in which muscle metabolism can no longer provide ATP. 4) ATP is hydrolyzed and the energy transferred to the myosin heads as they cock and reset for the next stimulus.

Excitation-Contraction Coupling: the Neuromuscular Junction   Each muscle cell is stimulated by a motor neuron axon. The point where the axon terminus contacts the sarcolemma is at a synapse called the neuromuscular junction. The terminus of the axon at the sarcolemma is called the motor end plate. The sarcolemma is polarized, in part due to the unequal distribution of ions due to the Sodium/Potassium Pump. (See  Excitability and Membrane Potential] and Figure 9.9) 1) Impulse arrives at the motor end plate (axon terminus) causing  Ca+2 to enter the axon. 2) Ca+2 binds to ACh vesicles causing them to release the ACh (acetylcholine) into the synapse by exocytosis.  3) ACH diffuses across the synapse to bind to receptors on the sarcolemma. Binding of ACH to the receptors opens chemically-gated ion channels causing Na+ to enter the cell producing depolarization. 4) When threshold depolarization occurs, a new impulse (action potential) is produced that will move along the sarcolemma. (This occurs because voltage-gated ion channels open as a result of the depolarization - See Figure 9.10) 5) The sarcolemma repolarizes: a) K+ leaves cell (potassium channels open as sodium channels close) returning positive ions to the outside of the sarcolemma. (More K+ actually leaves than necessary and the membrane is hyperpolarized briefly. This causes the relative refractory period) b) Na+/K+ pump eventually restores resting ion distribution.  The  Na+/K+ pump is very slow compared to the movement of ions through the ion gates. But a muscle can be stimulated thousands of times before the ion distribution is substantially affected. 6) ACH broken down by ACH-E (a.k.a. ACHase, cholinesterase). This permits the receptors to respond to another stimulus.  Insecticides and nerve gas are anti-cholinesterase toxins (chlinesterase inhibitors) and cause paralysis by leading to blockage of receptors by ACh. The antidote to these toxins is atropine which blocks the effect of ACh. Curare is an ACh competitor derived from plants, which has been used to relax muscles. Originally discovered because certain Indian tribes in South America tipped their arrows with it to kill game (it paralyzes the respiratory muscles), its use has given way to synthetic derivatives which are more controllable.

Excitation-Contraction Coupling: The action potential and release of calcium. The action potential is a self-propagated, all-or-none movement of depolarization along the membrane. (See Figure 9.10) All-or-none means that there are not different size action potentials. You either have one or you don't. As the action potential passes along the sarcolemma it causes release of Na+ into the cell by voltage-regulated ion gates, just as the chemically-regulated gates when stimulated by ACH. Then K+ gates open to repolarize that section of the membrane. The opening of Na+ gates then K+ gates happens at each location along the sarcolemma to propagate the action potential. (See Figure 9.9) As the action potential passes along the sarcolemma it enters the T-tubules which occur at each Z-line. (See Figure 9.4) The T-tubules are membranes which run across the cell (T for transverse) connecting to the sarcolemma. The T-tubules allow the action potential to continue into the cell interior. At points along the T tubules they attach to the sarcoplasmic reticulum, a system of membrane channels inside the sarcoplasm. When the action potential moves along the T tubules it causes the sarcoplasmic reticulum to release Ca+2 which is sequestered by the SR. The SR pumps calcium like the sarcolemma pumps sodium and releases it into the sarcoplasm when stimulated by the action potential. This causes the sliding of filaments as outlined above.

Excitation-Contraction Coupling: Summary of Events. 1) The impulse (action potential) travels along the sarcolemma. At each point the voltaged-gated Na+ channels open to cause depolarization, and then the K+ channels open to produce repolarization. 2) The impulse enters the cell through the T-tublules, located at each Z-disk, and reach the sarcoplasmic reticulum (SR), stimulating it. 3) The SR releases Ca+2 into the sarcoplasm, triggering the muscle contraction as previously discussed.  4) Ca+2 is pumped out of the sarcoplasm by the SR and another stimulus will be required to continue the muscle contraction. See Figure 9.11 and class diagram.

Graded Contractions and Muscle Metabolism

The muscle twitch is a single response to a single stimulus. (See Figure 9.13 a) Muscle twitches vary in length according to the type of muscle cells involved. (See Figure 9.13 b). Fast twitch muscles such as those which move the eyeball have twitches which reach maximum contraction in 3 to 5 ms (milliseconds). See [superior eye] and [lateral eye] These muscles were mentioned earlier as also having small numbers of cells in their motor units for precise control. The cells in slow twitch muscles like the postural muscles (e.g. back muscles, soleus) have twitches which reach maximum tension in 40 ms or so. The muscles which exhibit most of our body movements have intermediate twitch lengths of 10 to 20 ms. These three types also represents different metabolic patterns as will be discussed later. In a diagram of the muscle twitch can be seen the latent period, the period of a few ms encompassing the chemical and physical events preceding actual contraction. [This is not the same as the absolute refractory period, the even briefer period when the sarcolemma is depolarized and cannot be stimulated. The relative refractory period occurs after this when the sarcolemma is briefly hyperpolarized and requires a greater than normal stimulus. See Refractory Periods Diagram] Following the latent period is the contraction phase in which the shortening of the sarcomeres and cells occurs. Then comes the relaxation phase, a longer period because it is passive, the result of recoil due to the series elastic elements of the muscle.

We do not use the muscle twitch as part of our normal muscle responses. Instead we use graded contractions, contractions of whole muscles which can vary in terms of their strength and degree of contraction. In fact, even relaxed muscles are constantly being stimulated to produce muscle tone, the minimal graded contraction possible. Muscles exhibit graded contractions in two ways: 1) Quantal Summation or Recruitment - this refers to increasing the number of cells contracting. This is done experimentally by increasing the voltage used to stimulate a muscle, thus reaching the thresholds of more and more cells. (See Quantal Summation). In the human body quantal summation is accomplished by the nervous system, stimulating increasing numbers of cells or motor units to increase the force of contraction. 2) Wave Summation (a.k.a. frequency summation) and Tetanization- this results from stimulating a muscle cell before it has relaxed from a previous stimulus. This is possible because the contraction and relaxation phases are much longer than the refractory period. This causes the contractions to build on one another producing a wave pattern or, if the stimuli are high frequency, a sustained contraction called tetany or tetanus. (The term tetanus is also used for an illness caused by a bacterial toxin which causes contracture of the skeletal muscles.) This form of tetanus is perfectly normal and in fact is the way you maintain a sustained contraction. Treppe is not a way muscles exhibit graded contractions. (See Figure 9.15)It is a warmup phenomenon in which when muscle cells are initially stimulated when cold, they will exhibit gradually increasing responses until they have warmed up. The phenomenon is due to the increasing efficiency of the ion gates as they are repeatedly stimulated. Treppe can be differentiated from quantal summation because the strength of stimulus remains the same in treppe, but increases in quantal summation. Length-Tension Relationship: Another way in which the tension of a muscle can vary is due to the length-tension relationship. This relationship expresses the characteristic that within about 10% the resting length of the muscle, the tension the muscle exerts is maximum. At lengths above or below this optimum length the tension decreases. In practical terms a muscle will be its strongest at midpoint in its extensibility. For the heart, you will later learn, it means the muscle will adjust its output to normal increases in blood supply. Muscle Metabolism [See Muscle Metabolism chart] Muscle cells, like all others, use ATP as their energy currency. (See Figure 2.22 modified). But some muscle cells must exhibit activity levels in which they cannot make ATP as fast as it is consumed. So muscle cells have several mechanisms to provide the ATP they need. The phosphagen system - this is the use of immediately available ATP. This is not from stored ATP itself, muscle cells can store only very limited amounts. It is from energy stored as the related molecule CP, creatine phosphate. Creatine phosphate can be stored and is made from ATP during periods of rest. Then during periods of high activity CP is broken down quickly and its energy converted to ATP. But this source of ATP can only supply a cell for 8 to 10 seconds during the most strenuous exercise. Creatine released during muscle activity shows up in the urine as creatinine, a combination of two creatine molecules. Training can increase the amount of creatine phosphate stored, but this alone does not increase the strength of a muscle, just the length of time before it runs out of CP, and that by only a few seconds. See [Facts About Performance Boosters]

Anaerobic glycolysis - Glycolysis is the initial way of utilizing glucose in all cells, and is used exclusively by certain cells to provide ATP when insufficient oxygen is available for aerobic metabolism. Glycolysis doesn't produce much ATP in comparison to aerobic metabolism, but it has the advantage that it doesn't require oxygen. In addition, glycolysis occurs in the cytoplasm, not the mitochondria. So it is used by cells which are responsible for quick bursts of speed or strength. Like most chemical reactions, glycolysis slows down as its product, pyruvic acid, builds up. In order to extend glycolysis the pyruvic acid is converted to lactic acid in a process known as fermentation. Lactic acid itself eventually builds up, slowing metabolism and contributing to muscle fatigue. Ultimately the lactic acid must be reconverted to pyruvic acid and metabolized aerobically, either in the muscle cell itself, or in the liver. The oxygen which is "borrowed" by anaerobic glycolysis is called oxygen debt and must be paid back. Oxygen debt is partly oxygen reserves in the lungs, tissues, and myoglobin in the lungs (alactacid oxygen debt). But mostly it is the amount of oxygen which will be required to metabolize the lactic acid produced. Strength training increases the myofilaments in muscle cells and therefore the number of crossbridge attachments which can form. Training does not increase the number of muscle cells in any real way. (Sometimes a cell will tear and split resulting in two cells when healed). Lactic acid removal by the cardiovascular system improves with training which increases the anaerobic capacity. Even so, the glycolysis-lactic acid system can produce ATP for active muscle cells for only about a minute and a half.

Aerobic metabolism - ultimately, the product of glycolysis, pyruvic acid, must be metabolized aerobically. Aerobic metabolism is performed exclusively in the mitochondria. Pyruvic acid is converted to a molecule called an acetyl group and put into a pathway known as the Krebs Cycle. Energy is released in the form of ATP and, especially, as high energy electrons. These high energy electrons are sent to a process within the mitochondria known as the electron transport system which produces the vast majority of the ATP. The waste products of aerobic metabolism are CO2 and H2O. The reactant other than glucose is O2. Aerobic metabolism is used for endurance activities and has the distinct advantage that it can go on for hours. Aerobic training increases the length of endurance activities by increasing the number of mitochondria in the muscle cells, increasing the availability of enzymes, increasing the number of blood vessels, and increasing the amount of an oxygen-storing molecule called myoglobin.

The types of muscle cells. Different types of cells perform the differing functions of endurance activities and speed- strength activities. There are three types, red, white, and intermediate. The main differences can be exemplified by looking at red and white fibers and remembering that intermediate fibers have properties of the other two.

White Fibers Fast twitch Large diameter, used for speed and strength. Depends on the phosphagen system and on glycolysis-lactic acid. Stores glycogen for conversion to glucose. Fewer blood vessels. Little or no myoglobin.	Red Fibers Slow twitch Small diameter, used for endurance. Depends on aerobic metabolism. Utilize fats as well as glucose. Little glycogen storage. Many blood vessels and much myoglobin give this muscle its reddish appearance.
Intermediate Fibers: sometimes called "fast twitch red", these fibers have faster action but rely more on aerobic metabolism and have more endurance. Most muscles are mixtures of the different types. Muscle fiber types and their relative abundance cannot be varied by training, although there is some evidence that prior to maturation of the muscular system the emphasis on certain activities can influence their development.
The attached table lists the types of activities which involve the various phases of muscle metabolism. Also shown is the relative amount of alactacid oxygen debt (the 3 or 4 liters of available oxygen used up first) and the lactic acid oxygen debt produced after the first few minutes of strenuous exercise. There are also graphs which show the effect of diet on endurance and recovery of muscle.

Revised: October 03, 2006