BIOCHEMISTRY OF MUSCLE, MUSCLE CONTRACTION.

Muscle (from Latin musculus "little mouse") is contractile tissue of the body and is derived from the mesodermal layer

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of embryonic germ cells. It is classified as skeletal, cardiac, or smooth muscle[2], and its function is to produce force and cause motion, either locomotion or movement within internal organs. Much of muscle contraction occurs without conscious thought and is necessary for survival, like the contraction of the heart, or peristalsis (which pushes food through the digestive system). Voluntary muscle contraction is used to move the body, and can be finely controlled, like movements of the eye, or gross movements like the quadriceps muscle

of the thigh. There are two broad types of voluntary muscle fibers, slow twitch and fast twitch. Slow twitch fibers contract for long periods of time but with little force while fast twitch fibers contract quickly and powerfully but fatigue very rapidly.

Muscular System

The muscular system includes three types of muscles. They are smooth, which are found on the walls of internal organs, cardiac, which is found only in the heart, and skeletal muscles, which help strenthen the body and connect to bones.

This picture was obtained from The Bundles of Energy website.

I think that the muscular system compares well with a backhoe. The backhoe pulls back the shovel using metal cables, just like muscles contract pulling up the connected bone.

There are three types of muscle:

· Skeletal muscle or "voluntary muscle" is anchored by tendons to bone and is used to affect skeletal movement such as locomotion and in maintaining posture. Though this postural control is generally maintained as a subconscious reflex, the muscles responsible react to conscious control like non-postural muscles. An average adult male is made up of 40-50% of skeletal muscle and an average adult female is made up of 30-40%.

· Smooth muscle or "involuntary muscle" is found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, urethra, bladder, and blood vessels, and unlike skeletal muscle, smooth muscle is not under conscious control.

Smooth muscle

· Cardiac muscle is also an "involuntary muscle" but is a specialized kind of muscle found only within the heart.

Cardiac muscle

Cardiac and skeletal muscle are "striated" in that they contain sarcomeres

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and are packed into highly-regular arrangements of bundles; smooth muscle has neither. While skeletal muscles are arranged in regular, parallel bundles, cardiac muscle connects at branching, irregular angles. Striated muscle contracts and relaxes in short, intense bursts, whereas smooth muscle sustains longer or even near-permanent contractions.

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Skeletal muscle is further divided into several subtypes:

Blood flows from the heart to arteries, which narrow into arterioles, and then narrow further still into capillaries. After the tissue has been perfused, capillaries widen to become venules and then widen more to become veins, which return blood to the heart.

· Type I, slow oxidative, slow twitch, or "red" muscle is dense with capillaries

·

· and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity.

· Type II, fast twitch, muscle has three major kinds that are, in order of increasing contractile speed:

· Type IIa, which, like slow muscle, is aerobic, rich in mitochondria and capillaries and appears red.

· Type IIx (also known as type IId), which is less dense in mitochondria and myoglobin. This is the fastest muscle type in humans. It can contract more quickly and with a greater amount of force than oxidative muscle, but can sustain only short, anaerobic bursts of activity before muscle contraction becomes painful (often incorrectly attributed to a build-up of lactic acid). N.B. in some books and articles this muscle in humans was, confusingly, called type IIB.

· Type IIb, which is anaerobic, glycolytic, "white" muscle that is even less dense in mitochondria and myoglobin. In small animals like rodents this is the major fast muscle type, explaining the pale color of their meat.

Animals use muscles to convert the chemical energy of ATP

into mechanical work. Three different kinds of muscles are found in vertebrate animals

· Heart muscle — also called cardiac muscle — makes up the wall of the heart. Throughout life, it contracts some 70 times per minute pumping about 5 liters of blood each minute.

· Smooth muscle is found in the walls of all the hollow organs of the body (except the heart). Its contraction reduces the size of these structures. Thus it

· regulates the flow of blood in the arteries

· moves your breakfast along through your gastrointestinal tract

·

· expels urine from your urinary bladder

· sends babies out into the world from the uterus

· regulates the flow of air through the lungs

The contraction of smooth muscle is generally not under voluntary control.

· Skeletal muscle, as its name implies, is the muscle attached to the skeleton. It is also called striated muscle. The contraction of skeletal muscle is under voluntary control.

Anatomy of Skeletal Muscle

A single skeletal muscle, such as the triceps muscle, is attached at its

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· origin to a large area of bone; in this case, the humerus

· At its other end, the insertion, it tapers into a glistening white tendon which, in this case, is attached to the ulna, one of the bones of the lower arm.

As the triceps contracts, the insertion is pulled toward the origin and the arm is straightened or extended at the elbow. Thus the triceps is an extensor. Because skeletal muscle exerts force only when it contracts, a second muscle — a flexor — is needed to flex or bend the joint. The biceps muscle is the flexor of the lower arm. Together, the biceps and triceps make up an antagonistic pair of muscles. Similar pairs, working antagonistically across other joints, provide for almost all the movement of the skeleton.

The Muscle Fiber

Skeletal muscle is made up of thousands of cylindrical muscle fibers often running all the way from origin to insertion. The fibers are bound together by connective tissue through which run blood vessels and nerves.

Each muscle fibers contains:

· an array of myofibrils that are stacked lengthwise and run the entire length of the fiber.

· mitochondria

· an extensive smooth endoplasmic reticulum (SER)

· many nuclei.

The multiple nuclei arise from the fact that each muscle fiber develops from the fusion of many cells (called myoblasts).

The number of fibers is probably fixed early in life. This is regulated by myostatin,

a cytokine that is synthesized in muscle cells (and circulates as a hormone later in life). Myostatin suppresses skeletal muscle development. Cattle and mice with inactivating mutations in their myostatin genes develop much larger muscles. Some athletes and other remarkably strong people have been found to carry one mutant myostatin gene. These discoveries have already led to the growth of an illicit market in drugs supposedly able to suppress myostatin.

In adults, increased strength and muscle mass comes about through an increase in the thickness of the individual fibers and increase in the amount of connective tissue. In the mouse, at least, fibers increase in size by attracting more myoblasts to fuse with them. The fibers attract more myoblasts by releasing the cytokine interleukin 4 (IL-4). Anything that lowers the level of myostatin also leads to an increase in fiber size.

Because a muscle fiber is not a single cell, its parts are often given special names such as

· sarcolemma for plasma membrane

· sarcoplasmic reticulum for endoplasmic reticulum

· sarcosome for mitochondrion

· sarcoplasm for cytoplasm

·

although this tends to obscure the essential similarity in structure and function of these structures and those found in other cells.

The nuclei and mitochondria are located just beneath the plasma membrane

· the endoplasmic reticulum extends between the myofibrils.

Seen from the side under the microscope, skeletal muscle fibers show a pattern of cross banding, which gives rise to the other name: striated muscle.

The striated appearance of the muscle fiber is created by a pattern of alternating

· dark A bands and

· light I bands.

· The A bands are bisected by the H zone

· The I bands are bisected by the Z line.

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Each myofibril is made up of arrays of parallel filaments.

· The thick filaments have a diameter of about 15 nm. They are composed of the protein myosin.

· The thin filaments have a diameter of about 5 nm. They are composed chiefly of the protein actin along with smaller amounts of two other proteins:

·

· troponin and

· tropomyosin.

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The anatomy of a sarcomere

· The thick filaments produce the dark A band.

· The thin filaments extend in each direction from the Z line. Where they do not overlap the thick filaments, they create the light I band.

· The H zone is that portion of the A band where the thick and thin filaments do not overlap.

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The entire array of thick and thin filaments between the Z lines is called a sarcomere. Shortening of the sarcomeres in a myofibril produces the shortening of the myofibril and, in turn, of the muscle fiber of which it is a part. [This electron micrograph of a single sarcomere was kindly provided by Dr. H. E. Huxley.]

Activation of Skeletal Muscle

The contraction of skeletal muscle is controlled by the nervous system. The Dying Lioness (an Assyrian relief dating from about 650 B.C. and supplied through the courtesy of The Trustees of the British Museum) shows this vividly. Injury to the spinal cord has paralyzed the otherwise undamaged hind legs.

In this respect, skeletal muscle differs from smooth and cardiac muscle. Both cardiac and smooth muscle can contract without being stimulated by the nervous system. Nerves of the autonomic branch of the nervous system lead to both smooth and cardiac muscle, but their effect is one of moderating the rate and/or strength of contraction.

The Neuromuscular Junction

Nerve impulses (action potentials) traveling down the motor neurons of the sensory-somatic branch of the nervous system cause the skeletal muscle fibers at which they terminate to contract. The junction between the terminal of a motor neuron and a muscle fiber is called the neuromuscular junction. It is simply one kind of synapse. (The neuromuscular junction is also called the myoneural junction.)

The terminals of motor axons contain thousands of vesicles filled with acetylcholine (ACh).

When an action potential reaches the axon terminal, hundreds of these vesicles discharge their ACh onto a specialized area of postsynaptic membrane on the fiber. This area contains a cluster of transmembrane channels that are opened by ACh and let sodium ions (Na⁺) diffuse in.

The interior of a resting muscle fiber has a resting potential of about −95 mV. The influx of sodium ions reduces the charge, creating an end plate potential. If the end plate potential reaches the threshold voltage (approximately −50 mV), sodium ions flow in with a rush and an action potential is created in the fiber. The action potential sweeps down the length of the fiber just as it does in an axon.

No visible change occurs in the muscle fiber during (and immediately following) the action potential. This period, called the latent period, lasts from 3–10 msec.

Before the latent period is over,

· the enzyme acetylcholinesterase

· breaks down the ACh in the neuromuscular junction (at a speed of 25,000 molecules per second)

· the sodium channels close, and

· the field is cleared for the arrival of another nerve impulse.

· the resting potential of the fiber is restored by an outflow of potassium ions

The brief (1–2 msec) period needed to restore the resting potential is called the refractory period.

Tetanus

The process of contracting takes some 50 msec; relaxation of the fiber takes another 50–100 msec. Because the refractory period is so much shorter than the time needed for contraction and relaxation, the fiber can be maintained in the contracted state so long as it is stimulated frequently enough (e.g., 50 stimuli per second). Such sustained contraction is called tetanus.

Clonus and tetanus are possible because the refractory period is much briefer than the time needed to complete a cycle of contraction and relaxation. Note that the amount of contraction is greater in clonus and tetanus than in a single twitch.

As we normally use our muscles, the individual fibers go into tetanus for brief periods rather than simply undergoing single twitches.

Coupling Excitation to Contraction

Calcium ions (Ca²⁺) link action potentials in a muscle fiber to contraction.

· In resting muscle fibers, Ca²⁺ is stored in the endoplasmic (sarcoplasmic) reticulum.

· Spaced along the plasma membrane (sarcolemma) of the muscle fiber are inpocketings of the membrane that form tubules of the "T system". These tubules plunge repeatedly into the interior of the fiber.

· The tubules of the T system terminate near the calcium-filled sacs of the sarcoplasmic reticulum.

· Each action potential created at the neuromuscular junction sweeps quickly along the sarcolemma and is carried into the T system.

· The arrival of the action potential at the ends of the T system triggers the release of Ca²⁺.

· The Ca²⁺ diffuses among the thick and thin filaments where it

· binds to troponin on the thin filaments.

· This turns on the interaction between actin and myosin and the sarcomere contracts.

· Because of the speed of the action potential (milliseconds), the action potential arrives virtually simultaneously at the ends of all the tubules of the T system, ensuring that all sarcomeres contract in unison.

· When the process is over, the calcium is pumped back into the sarcoplasmic reticulum using a Ca²⁺ ATPase [Link to discussion].

Isotonic versus Isometric Contractions

If a stimulated muscle is held so that it cannot shorten, it simply exerts tension. This is called an isometric ("same length") contraction. If the muscle is allowed to shorten, the contraction is called isotonic ("same tension").

Motor Units

All motor neurons leading to skeletal muscles have branching axons, each of which terminates in a neuromuscular junction with a single muscle fiber. Nerve impulses passing down a single motor neuron will thus trigger contraction in all the muscle fibers at which the branches of that neuron terminate. This minimum unit of contraction is called the motor unit.

The size of the motor unit is small in muscles over which we have precise control. Examples:

· a single motor neuron triggers fewer than 10 fibers in the muscles controlling eye movements

· the motor units of the muscles controlling the larynx are as small as 2–3 fibers per motor neuron

· In contrast, a single motor unit for a muscle like the gastrocnemius (calf) muscle may include 1000–2000 fibers (scattered uniformly through the muscle).

Although the response of a motor unit is all-or-none, the strength of the response of the entire muscle is determined by the number of motor units activated.

Even at rest, most of our skeletal muscles are in a state of partial contraction called tonus. Tonus is maintained by the activation of a few motor units at all times even in resting muscle. As one set of motor units relaxes, another set takes over.

Fueling Muscle Contraction

ATP is the immediate source of energy for muscle contraction. Although a muscle fiber contains only enough ATP to power a few twitches, its ATP "pool" is replenished as needed. There are three sources of high-energy phosphate to keep the ATP pool filled.

· creatine phosphate

·

· glycogen

· cellular respiration in the mitochondria of the fibers.

Creatine phosphate

The phosphate group in creatine phosphate is attached by a "high-energy" bond like that in ATP. Creatine phosphate derives its high-energy phosphate from ATP and can donate it back to ADP to form ATP.

Creatine phosphate + ADP ↔ creatine + ATP

The pool of creatine phosphate in the fiber is about 10 times larger than that of ATP and thus serves as a modest reservoir of ATP.

Glycogen

Skeletal muscle fibers contain about 1% glycogen. The muscle fiber can degrade this glycogen by glycogenolysis producing glucose-1-phosphate. This enters the glycolytic pathway to yield two molecules of ATP for each pair of lactic acid molecules produced. Not much, but enough to keep the muscle functioning if it fails to receive sufficient oxygen to meet its ATP needs by respiration.

However, this source is limited and eventually the muscle must depend on cellular respiration.

Cellular respiration

Cellular respiration not only is required to meet the ATP needs of a muscle engaged in prolonged activity (thus causing more rapid and deeper breathing), but is also required afterwards to enable the body to resynthesize glycogen from the lactic acid produced earlier (deep breathing continues for a time after exercise is stopped). The body must repay its oxygen debt.

Most skeletal muscles contain some mixture of Type I and Type II fibers, but a single motor unit always contains one type or the other, never both.

The ratio of Type I and Type II fibers can be changed by endurance training (producing more Type I fibers).

· The action potential that triggers the heartbeat is generated within the heart itself. Motor nerves (of the autonomic nervous system) do run to the heart, but their effect is simply to modulate — increase or decrease — the intrinsic rate and the strength of the heartbeat. Even if the nerves are destroyed (as they are in a transplanted heart), the heart continues to beat.

· The action potential that drives contraction of the heart passes from fiber to fiber through gap junctions.

· Significance: All the fibers contract in a synchronous wave that sweeps from the atria down through the ventricles and pumps blood out of the heart. Anything that interferes with this synchronous wave (such as damage to part of the heart muscle from a heart attack) may cause the fibers of the heart to beat at random — called fibrillation. Fibrillation is the ultimate cause of most deaths and its reversal is the function of defibrillators that are part of the equipment in ambulances, hospital emergency rooms, and — recently — even on U.S. air lines.

· The refractory period in heart muscle is longer than the period it takes for the muscle to contract (systole) and relax (diastole). Thus tetanus is not possible (a good thing, too!).

· Cardiac muscle has a much richer supply of mitochondria than skeletal muscle. This reflects its greater dependence on cellular respiration for ATP.

· Cardiac muscle has little glycogen and gets little benefit from glycolysis when the supply of oxygen is limited.

· Thus anything that interrupts the flow of oxygenated blood to the heart leads quickly to damage — even death — of the affected part. This is what happens in heart attacks.

Below: the human heart, with a schematic view of the pathway of blood through the lungs and internal organs. Oxygenated blood is shown in red; deoxygenated blood in blue. Note that the blood draining the stomach, spleen, and intestines passes through the liver before it is returned to the heart. Here surplus or harmful materials picked up from those organs can be removed before the blood returns to the general circulation.

Smooth Muscle

Smooth muscle is made of single, spindle-shaped cells. It gets its name because no striations are visible in them. Nonetheless, each smooth muscle cell contains thick (myosin) and thin (actin) filaments that slide against each other to produce contraction of the cell. The thick and thin filaments are anchored near the plasma membrane (with the help of intermediate filaments)).

Smooth muscle (like cardiac muscle) does not depend on motor neurons to be stimulated. However, motor neurons (of the autonomic system) reach smooth muscle and can stimulate it — or relax it — depending on the neurotransmitter they release (e.g. noradrenaline or nitric oxide, NO)).

Smooth muscle can also be made to contract

· by other substances released in the vicinity (paracrine stimulation)

· Example: release of histamine causes contraction of the smooth muscle lining our air passages (triggering an attack of asthma)

· by hormones circulating in the blood

· Example: oxytocin reaching the uterus stimulates it to contract to begin childbirth.

The contraction of smooth muscle tends to be slower than that of striated muscle. It also is often sustained for long periods. This, too, is called tonus but the mechanism is not like that in skeletal muscle.

MUSCLE TAPEWORM CYSTS

Muscle Diseases

The carotid arteries run on each side of the neck and supply the brain with blood.  These often become furred up and this causes a narrowing of the carotid artery.  These can cause mini - strokes (transient ischaemic attacks) or a full blown stroke.  This can be prevented by a simple operation called carotid endarterectomy.

Carotid Endarterectomy: 1

Carotid endarterectomy, pioneered by Dr. (Sir) Charles Rob, remains a durable operation for atherosclerotic carotid disease. Symptomatic plaque throwing emboli or reaching critical stenosis (50-70%) are clear indications. With asymptomatic significant stenoses operated by experienced surgeons, the benefits probably outweigh morbidity.

Carotid Endarterectomy: 2

The incision is deepened through platysma and the investing layer of deep cervical fascia at the edge of the sternocleidomastoid muscle. The muscle is bluntly dissected off the loose underlying carotid sheath exposing the internal jugular vein.

Carotid Endarterectomy: 3

The carotid sheath is opened, the common facial vein crossing the carotid bifurcation is ligated and divided, and the internal jugular vein is gently retracted posteriorly. The ansa hypoglossi may be mobilized out of the way or may be divided without significant consequences. The internal and external carotid origins are visualized along with the origin of the superior thyroid artery. The hypoglossal nerve is visualized high in the field along with the vagus nerve deep between the vessels.

Carotid Endarterectomy: 4

Vessel loops are tightened for proximal and distal control around soft portions of the vessel. Some surgeons use angled Pott's clamps for this purpose but these are slightly more traumatic and cannot be used with a shunt. An incision is started with an 11 blade in the common carotid and carried up along the internal carotid with angled Pott's scissors.

Carotid Endarterectomy: 6

The use of a shunt allows more time for careful dissection by maintaining normal cerebral blood flow and decreasing the risk of CVA. Many excellent surgeons use it routinely, especially in training programs, and many use it selectively, especially if their clamp time is routinely under 10 minutes. Measurement of stump pressure indicating degree of flow across the circle of Willis provides some guidance for whether to shunt. Criteria vary among surgeons, 40mm of Hg generally being considered a minimal safe pressure. The shunt is looped or bowed with a suture sling to provide working room around it. The remaining images are shown without a shunt for clarity.

CAROTID ATHEROSCLEROSIS

The Muscular Dystrophies (MD)

Together myosin, actin, tropomyosin, and troponin make up over three-quarters of the protein in muscle fibers. Some two dozen other proteins make up the rest. These serve such functions as attaching and organizing the filaments in the sarcomere and connecting the sarcomeres to the plasma membrane and the extracellular matrix. Mutations in the genes encoding these proteins may produce defective proteins and resulting defects in the muscles.

Among the most common of the muscular dystrophies are those caused by mutations in the gene for dystrophin.

The gene for dystrophin is huge, containing 79 exons spread out over 2.3 million base pairs of DNA. Thus this single gene represents about 0.1% of the entire human genome (3 x 10⁹ bp) and is almost half the size of the entire genome of E. coli!

· Duchenne muscular dystrophy (DMD)

·

Perhaps its great size makes this gene so susceptible to partial deletions. If these cause a change in the reading frame, no dystrophin is synthesized and DMD, a very severe form of the disease, results.

· Becker muscular dystrophy (BMD).

If the deletion simply removes certain exons, a shortened protein results that produces BMD, a milder form of the disease.

The gene for dystrophin is on the X chromosome, so these two diseases strike males in a typical X-linked pattern of inheritance.

The Cardiac Myopathies

Heart Disease in Cats

The heart is the most important muscle in your cat's body. It is the pump that collects blood from the body and sends it through the lungs, where it picks up oxygen. The heart then pumps the oxygen-rich blood back through the body. Most forms of heart failure involve a decrease in the pumping ability of the heart, which results in a buildup of fluid in the lungs or abdomen and an inadequate flow of blood to vital organs.

Cats of any age can be affected with diseases of the heart muscle. Heart disease due to an underlying problem, such as hyper-thyroidism, may be corrected when the underlying problem is addressed. With proper management, some cats with a history of heart disease can lead a relatively normal life.

Contributing Factors

Defects in heart valves and muscle, tumors, trauma, and heartworm infestation can all cause heart disease and lead to heart failure. In cats, a heart muscle defect (cardiomyopathy) is the most common heart problem. The occurrence of heart disease is often sudden and requires immediate veterinary attention.

One of the more recent findings is that a deficiency of taurine in the diet can result in heart disease in cats, so an adequate diet, again, is essential to the overall health of your cat.

There may be a genetic predisposition to heart disease in Siamese, Abyssinian, and Burmese cats.

Clinical Signs

Heart disease may cause fluid to accumulate in the lungs or abdomen. The following signs may indicate heart disease, but can also be produced by other diseases:

• Coughing, typically low-pitched and sometimes uncontrollable to the point of ending with gagging
• Difficulty breathing, shortness of breath
• Reduced exercise tolerance
• Noticeable weight gain or loss, or abdominal distension

Diagnosis

In addition to a thorough physical exam, City Cats uses x-rays, ECGs, blood tests, and ultrasounds to diagnose heart disease in cats. Most of these tests will need to be repeated to monitor the effectiveness of treatment. Exams always include the doctor listening to your cat's heart; abormalities such as heart mumurs are not always noticable, and frequent monitoring can help detect them.

For management and monitoring of cats with heart disease, City Cats schedules echocardiograms with certified veterinary cardiologist Dr. Naney Laste at Angell Memorial Hospital. All cats with heart murmurs or suspected heart weaknesses screened via echocardiogram prior to undergoing anesthesia for surgical procedures.

Treatment

Sometimes hospitalization is required so that we can stabilize your cat's condition and attempt to reduce the excess fluid. If heart disease is detected before serious complications develop, a change in diet may be all that is required. As in human heart disease, restricted sodium in the diet is necessary.

Several medications are available for the treatment of heart disease, depending on the individual situation. You must follow your prescription instructions carefully. Some drugs used in the treatment of heart disease include:

Diuretics, or "water tablets," increase fluid excretion and help disperse the retention of fluid associated with heart failure.

Cardiac Glycosides act on the heart muscle directly. They slow the heart, improve the strength of its contractions, and improve its overall efficiency of pumping action.

Vasodilators are relatively new to the veterinary world. They have a complex action, helping circulation throughout the body. This takes the strain off the heart and, in so doing, allows it to pump more effectively.

Prognosis

A low-sodium diet may complement drug therapy and help to minimize fluid retention and reduce coughing and discomfort. City Cats may prescribe a special low-sodium diet to help you manage your cat's sodium intake and reduce fluid retention, while also ensuring that all your cat's nutritional needs are met.

If your cat is overweight, you may be advised to try a low-calorie diet, as extra weight may increase stress on the heart and lungs. Animals with heart disease may have a decreased appetite from feeling unwell and as a side effect of heart drugs that are necessary for them. Special diets must not only benefit health but also must taste good. City Cats will work with you to encourage your cat to eat an appropriate diet.

Also be aware that your cat's drinking water must also be checked, as softened water is usually high in sodium. Protect your cat from stress such as excitement, extreme exertion, high humidity, and hot or cold temperatures. And avoid extra treats unless they are approved by City Cats staff, since many snacks have a high sodium content.

Prevention

Many forms of heart disease are progressive; however, with proper management and diet, your pet may be able to have a better quality of life. To prevent heart disease related to taurine deficiencies, ensure that your cat has a diet that meets all his or her nutritional needs.

Cardiac muscle, like skeletal muscle, contains many proteins in addition to actin and myosin. Mutations in the genes for these may cause the wall of the heart to become weakened and, in due course, enlarged. Among the genes that have been implicated in these diseases are those encoding:

· actin

· two types of myosin

· troponin

· tropomyosin

· myosin-binding protein C (which links myosin to titin)

The severity of the disease varies with the particular mutation causing it (over 100 have been identified so far) . Some mutations are sufficiently dangerous that they can lead to sudden catastrophic heart failure in seemingly healthy and active young adults.

Anatomy

Muscle is mainly composed of muscle cells. Within the cells are myofibrils; myofibrils contain sarcomeres, which are composed of actin and myosin. Individual muscle fibres are surrounded by endomysium. Muscle fibers are bound together by perimysium into bundles called fascicles; the bundles are then grouped together to form muscle, which is enclosed in a sheath of epimysium. Muscle spindles are distributed throughout the muscles and provide sensory feedback information to the central nervous system.

Skeletal muscle is muscle attached to skeletal tissue, distinct from heart or smooth muscle. It is arranged in discrete muscles, an example of which is the biceps brachii. It is connected by tendons to processes of the skeleton. In contrast, smooth muscle occurs at various scales in almost every organ, from the skin (in which it controls erection of body hair) to the blood vessels and digestive tract (in which it controls the caliber of the lumen and peristalsis). Cardiac muscle is the muscle tissue of the heart, and is similar to skeletal muscle in both composition and action, being comprised of myofibrils of sarcomeres. Cardiac muscle is anatomically different in that the muscle fibers are typically branched like a tree branch, and connect to other cardiac muscle fibers through intercalcated discs, and form the appearance of a syncytium.

There are approximately 639 skeletal muscles in the human body (see list of muscles of the human body). Contrary to popular belief, the number of muscle fibres cannot be increased through exercise; instead the muscle cells simply get bigger. Muscle fibres have a limited capacity for growth through hypertrophy and some believe they split through hyperplasia if subject to increased demand.°

Physiology

The three (skeletal, cardiac and smooth) types of muscle have significant differences. However, all three use the movement of actin against myosin to create contraction. In skeletal muscle, contraction is stimulated by electrical impulses transmitted by the nerves, the motor nerves and motoneurons in particular. Cardiac and smooth muscle contractions are stimulated by internal pacemaker cells which regularly contract, and propogate contractions to other muscle cells they are in contact with. All skeletal muscle and many smooth muscle contractions are facilitated by the neurotransmitter acetylcholine.

Muscular activity accounts for much of the body's energy consumption. All muscle cells produce adenosine triphosphate (ATP) molecules which are used to power the movement of the myosin heads. Muscles contain an ATP store in the form of creatine phosphate which is generated from ATP and can regenerate ATP when needed with creatine kinase. Muscles also keep a storage form of glucose in the form of glycogen. Glycogen can be rapidly converted to glucose when energy is required for sustained, powerful contractions. Within the voluntary skeletal muscles, the glucose molecule is metabolized in a process called glycolysis which produces two ATP and two lactic acid molecules in the process. Muscle cells also contain globules of fat, which are used for energy during aerobic exercise. The aerobic energy systems take longer to produce the ATP and reach peak efficiency, and requires many more biochemical steps, but produces significantly more ATP than anaerobic glycolysis. Cardiac muscle on the other hand, can readily consume any of the three macronutrients (protein, glucose and fat) without a 'warm up' period and always extracts the maximum ATP yield from any molecule involved. The heart and liver will also consume lactic acid produced and excreted by skeletal muscles during exercise.

Nervous control

Afferent leg

The afferent leg of the peripheral nervous system is responsible for conveying sensory information to the brain, primarily from the sense organs like the skin. In the muscles, the muscle spindles convey information about the degree of muscle length and stretch to the central nervous system to assist in maintaining posture and joint position. The sense of where our bodies are in space is called proprioception, the perception of body awareness. More easily demonstrated than explained, proprioception is the "unconscious" awareness of where the various regions of the body are located at any one time. This can be demonstrated by anyone closing their eyes and waving their hand around. Assuming proper proprioceptive function, at no time will the person lose awareness of where the hand actually is, even though it is not being detected by any of the other senses.

Several areas in the brain coordinate movement and position with the feedback information gained from proprioception. The cerebellum and red nucleus in particular continuously sample position against movement and make minor corrections to assure smooth motion.

Role in health and disease

Disease

There are many diseases and conditions which cause a decrease in muscle mass, known as atrophy. For example diseases such as cancer and AIDS induce a body wasting syndrome called cachexia, which is notable for the severe muscle atrophy seen. Other syndromes or conditions which can induce skeletal muscle atrophy are congestive heart disease and liver disease.

During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called sarcopenia. The exact cause of sarcopenia is unknown, but it may be due to a combination of the gradual failure in the "satellite cells" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.

In addition to the simple loss of muscle mass (atrophy), or the age-related decrease in muscle function (sarcopenia), there are other diseases which may be caused by structural defects in the muscle (the dystrophies), or by inflammatory reactions in the body directed against muscle (the myopathies).

Symptoms of muscle disease may include weakness or spasticity/rigidity, myoclonus (twitching) and myalgia (muscle pain). Diagnostic procedures that may reveal muscular disorders include testing creatine kinase levels in the blood and electromyography (measuring electrical activity in muscles). In some cases, muscle biopsy may be done to identify a myopathy, as well as genetic testing to identify DNA abnormalities associated with specific myopathies.

Neuromuscular diseases are those that affect the muscles and/or their nervous control. In general, problems with nervous control can cause spasticity or paralysis, depending on the location and nature of the problem. A large proportion of neurological disorders leads to problems with movement, ranging from cerebrovascular accident (stroke) and Parkinson's disease to Creutzfeldt-Jakob disease.

Inactive Muscle

People may lose 20 to 40 percent of their muscle -- and, along with it, their strength -- as they age. Scientists have found that a major reason people lose muscle is because they stop doing everyday activities that use muscle power, not just because they grow older.

Muscular Atrophy

Muscular atrophy is the decrease in size and wasting of muscle tissue. Muscles that lose their nerve supply can atrophy and simply waste away.

Dermatomyositis is a subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in ass

Disease of Heart Muscle

Abscesses and green pus in caribou muscle

· The heart has a claim to being the muscle that performs the largest quantity of physical work in the course of a lifetime. Estimates of the power output of the human heart range from 1 to 5 watts. This is much less than the maximum power output of other muscles; for example, the quadriceps can produce over 100 watts, but only for a few minutes. The heart does its work continuously over an entire lifetime without pause, and thus does "outwork" other muscles. An output of one watt continuously for seventy years yields a total work output of two to three gigajoules.

Coronary artery disease

The coronary arteries provide oxygen-rich blood and other nutrients to the heart muscle. They attach to and wrap around the heart's surface.

Coronary artery disease occurs when blood flow to the heart muscle

Efficiency

The efficiency of human muscle has been measured (in the context of rowing and cycling) at 14% to 27%. The efficiency is defined as the ratio of mechanical work output to the total metabolic cost.

• Left Ventricular Dysfunction
• What Is Athlete's Heart?
• Atrial myxoma - a tumor in the heart
• Cardiac Amyloidosis

Strength

A display of "strength" (e.g lifting a weight) is a result of three factors that overlap; Physiological strength (muscle size, cross sectional area, available crossbridging, responses to training), neurological strength (how strong or weak is the signal that tells the muscle to contract), and mechanical strength (muscle's force angle on the lever, moment arm length, joint capabilities).

Gastroesophageal reflux disease

A band of muscle fibers, the lower esophageal sphincter, closes off the esophagus from the stomach. If the sphincter does not close properly, food and liquid can move backward into the esophagus and cause heartburn and other symptoms known as gastroesophageal disease (GERD). To alleviate symptoms dietary changes and medications are prescribed. For a patient who has persistent symptoms despite medical treatment, an anti-reflux operation may be an option.

The 'strongest' human muscle

Since three factors affect muscular strength simultaneously and muscles never work individually, it is unrealistic to compare strength in individual muscles, and state that one is the "strongest". Accordingly, no one muscle can be named 'the strongest', but below are several muscles whose strength is noteworthy for different reasons.

· In ordinary parlance, muscular "strength" usually refers to the ability to exert a force on an external object—for example, lifting a weight. By this definition, the masseter or jaw muscle is the strongest. The 1992 Guinness Book of Records records the achievement of a bite strength of 4337 N (975 lbf) for 2 seconds. What distinguishes the masseter is not anything special about the muscle itself, but its advantage in working against a much shorter lever arm than other muscles.

· If "strength" refers to the force exerted by the muscle itself, e.g., on the place where it inserts into a bone, then the strongest muscles are those with the largest cross-sectional area. This is because the tension exerted by an individual skeletal muscle fiber does not vary much. Each fiber can exert a force on the order of 0.3 micronewton. By this definition, the strongest muscle of the body is usually said to be the quadriceps femoris or the gluteus maximus.

· A shorter muscle will be stronger "pound for pound" (i.e., by weight) than a longer muscle. The uterus may be the strongest muscle by weight in the human body. At the time when an infant is delivered, the human uterus weighs about 1.1 kg (40 oz). During childbirth, the uterus exerts 100 to 400 N (25 to 100 lbf) of downward force with each contraction.

Parkinson’s disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Epidermolysis bullosae is a group of rare, hereditary skin diseases in which blisters develop, usually at sites of a wound. Severe forms may also involve mucous membranes and may leave scars and muscle weakness.

· The external muscles of the eye are conspicuously large and strong in relation to the small size and weight of the eyeball. It is frequently said that they are "the strongest muscles for the job they have to do" and are sometimes claimed to be "100 times stronger than they need to be." However, eye movements (particularly saccades used on facial scanning and reading) do require high speed movements, and eye muscles are 'exercised' nightly during Rapid eye movement.

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· The unexplained statement that "the tongue is the strongest muscle in the body" appears frequently in lists of surprising facts, but it is difficult to find any definition of "strength" that would make this statement true. Note that the tongue consists of sixteen muscles, not one.

Muscle evolution

Evolutionarily, specialized forms of skeletal and cardiac muscles predated the divergence of the vertebrate/arthropod evolutionary line.[6] This indicates that these types of muscle developed in a common ancestor sometime before 700 million years ago (mya). Vertebrate smooth muscle (smooth muscle found in humans) was found to have evolved independently from the skeletal and cardiac muscles.