Skeletal muscle

Skeletal muscle is so called because it is attached to the bones which make up the skeleton.
Bones not only give the body shape and protection, but they act as levers which allow movement - altering the position of parts of the body or transferring the whole body from place to place.

It is also called voluntary muscle because it is under control by the nervous system. Nerve impulses are generated (by 'conscious thought') in the cerebrum of the brain and these pass to the motor cortex and then down the spinal cord. Motor neurones originating in the spinal cord carry nervous impulses out along nerve fibres (composed of axons of motor neurones) to muscles and at the neuromuscular junctions these impulses cause depolarisation of the muscle cell membrane, stimulating the muscle to react.

Skeletal muscles are also located at the openings of eyes and internal tracts to control the movement of various substances, thus allowing functions such as swallowing, urination, and defaecation, to be under voluntary control.

Muscles work by shortening

Muscles are attached at one end to a fixed point on the skeleton, and at the other end to a part that needs to be moved, typically another bone which articulates with it at a joint within a limb. When stimulated, muscles contract so they become shorter (and fatter). This creates tension which tends to bring the two bones closer together. Since bone is quite tough and incompressible, the bones usually move relative to one another at the joint, and so the limb bends or straightens.

Muscles work in pairs - and take it in turns

In order to undo an action, it is necessary to activate another muscle which pulls in the opposite direction. When this muscle contracts, the first muscle relaxes as it is pulled back to its original position. Antagonistic pairs of muscles are found wherever movement occurs in the body.

The arm as a lever

The biceps muscle of the arm (biceps brachii) has 2 origins on the shoulder blade (scapula). Biceps means 'two heads'. It has an insertion on the radius, not far from the elbow. A fairly small shortening of this muscle can thus cause a large movement of the arm.

Its antagonistic partner is the triceps (triceps brachii), which has 3 origins; one on the shoulder blade, and the other two on the humerus. At the other end, the muscle sections merge to form a single tendon which has an insertion (attachment point) on the end of the ulna.

The biceps contracts to bend the arm, and the triceps contracts to straighten it.


Some skeletal muscles are only attached to bone at one end, e.g. muscles involved in facial expressions, smiling etc.

Structure of skeletal muscle

Rings and wrinkles in a flesh-fibre

In 1682, the early microscopist Antonie van Leeuwenhoek published this picture (from ox tongue?).



(translation from Dutch) Fig. 1 is a flesh-fibre in which frequently the rings and wrinkles became apparent to me, such as ABCD and others close to them as at EFGH and also IKLM; and so (as I have said before) they looked like globules when seen through an ordinary microscope. Also a flesh-fibre would appear as NOPQ, which last, I could state, showed the internal filaments which constitute a flesh-fibre.
After this he teased apart the internal filaments.
From this I concluded that a flesh-fibre, which, as I have said before, is not thicker than 1/9 of a hair from my beard, consisted of as many as 100 filaments.

Microscopic structure

Other types of muscle:

Smooth (non-striated) or involuntary muscle

Smooth muscle cells are found in the walls of the alimentary canal, (stomach, intestines etc), arteries and veins, and pipework of the urinary and reproductive system as well as the iris of the eye and in skin (hair erector pili muscles). These are under the control of the autonomic nervous system.

Cardiac (heart) muscle

Cardiac muscle resembles skeletal muscle in that it has stripes, but the filaments appear to branch rather than run as parallel fibres. There are also prominent intercalated discs which allow each wave of depolarisation to pass to the next cell. This probably assists in synchronising the regular myogenic contractions which make the pumping actions as the heart beats.

Ultrastructure of a myofibril

The basic subunit within myofibrils is a sarcomere.

The Z-lines (zigzags in this diagram) or Z-discs are the ends of the sarcomeres, which contain parallel filaments made of different proteins.

Attached to the Z-lines are thin filaments - Actin.

Alongside these and spreading out from the central M-line are thick filaments - Myosin.

More illuminating names for the different areas of a sarcomere

Each of these zones has been given a name (mostly in German).
Mercifully, they have been reduced to single initial letters.
These sections have been described according to their appearance under polarised light.
I stands for isotropic (uniform in all orientations)
A stands for anisotropic (not uniform in all orientations)
The H-zone is a lighter coloured area in the centre of the sarcomere.

During muscle contraction, the I bands and the H zones shorten.
The size of the A bands does not change.

Getting the process started

A nerve impulse from the central nervous system passes along the axon of a motor neurone towards the muscle. When it reaches the motor end plate it forms a neuromuscular junction, quite like a broad synapse. Acetyl choline is released and diffuses across the gap between the end of the neurone and the post-synaptic muscular membrane.

ACh binds to receptors on the postsynaptic membrane, which open sodium channels.
As sodium ions enter, there is a depolarisation of the muscle cell membrane. The action potential is carried into the muscle via T-tubules.

Sarcoplasmic reticulum on the outside of the myofibrils releases calcium ions. This causes the protein tropomyosin to change shape and move away from its resting position on the actin fibres. This position is also called the (myosin) binding site. This movement therefore allows myosin to bind with actin, forming cross-bridges (See below).

[Calcium ions are also said to activate the ATP hydrolase activity associated with the change in the shape of myosin - the angle of its head - which pulls on the actin filaments, causing the muscle to contract.]
I have put the above sentence into square brackets because I can find no confirmatory evidence for it on the web. Perhaps your textbook mentions it. If so, please get in touch.

Later on

When Ca²⁺ is absorbed by the sarcoplasmic reticulum, tropomyosin's conformation changes, taking it back to its original position. This inhibits the actin-myosin interaction, and muscle contraction ceases.

Working in from the outside

Each muscle fibre is an individual cell, with a cell plasma membrane (also called a sarcolemma) on the outside. When the motor neurone sends an impulse to the neuromuscular junction, it releases acetylcholine, which diffuses to receptors on the surface of the membrane, opening sodium ion channels so that sodium ions enter the muscle cells from the surrounding tissue fluid. This membrane thus becomes depolarised like a neurone and an action potential spreads over it. Extending down from this are rings called T-tubules which surround the individual muscle fibrils, at either end of the A-band. Embedded in their phospholipid bilayer are a large number of calcium ion channels and calcium ion pumps. T-tubules speed up and synchronise the passage of impulses to the surface of the myofibrils.

Beneath the cell membrane and spreading out over the surface of the myofibrils is a network of tubes called the sarcoplasmic reticulum which come into close contact with the T-tubules. The sarcoplasmic reticulum contains a store of calcium ions, which are released via 'calcium release channels' when the cell membrane is depolarised. These calcium ions interact with the proteins troponin and tropomyosin which change shape and orientation, allowing actin and myosin to form crossbridges and migrate past one another, causing muscular contraction.

The removal of calcium ions after muscular contraction (i.e. during muscle relaxation) is caused by an intracellular membrane-associated pump, also known as the enzyme SERCA, which moves calcium ions back into the sarcoplasmic reticulum on the outside of muscle cells (myocytes). It is a Ca²⁺ ATPase that transfers Ca²⁺ from the cytosol of the muscle cell into the SR, powered by ATP hydrolysis.

Myofibril contraction

The proteins actin and myosin interact inside the sarcomeres and cause the sarcomeres and whole myofibril to shorten, which results in the contraction of the muscle.

Their relative movement is explained by the sliding filament theory.

Myosin heads projecting from the sides of thick filaments go through a cycle of forming and then breaking bonds ('actomyosin' cross-linkages or bridges) with the thin filaments of actin.

This repeated action - which resembles the movement of feet when walking, or oars when rowing - draws the actin on each end of the sarcomere inwards towards the centre of the sarcomeres.

The bridge breaking is assisted by ATP, which also causes the head to become 'cocked' and gives energy for the movement ('the power stroke') when the myosin head binds with specific sites on the actin filament.

After this another crossbridge can be formed, further along the actin filament, so that myosin pulls the actin towards the centre of the sarcomere, shortening the muscle fibre.

Actin-Myosin cycle

(Myosin shown in blue)

1 ATP hydrolysis causes 'cocking' of myosin head:
ADP and Pi still attached
2 Myosin forms cross-bridge with Actin making actomyosin:
Pi released, ADP still attached to actin

3 'Power stroke': myosin neck changes angle, thick filament moves towards Z-line, pulling thin filament of actin towards centre of sarcomere and shortening myofibril: ADP released

4 ATP binds to myosin, breaking previous cross-bridge

The cycle may then repeat, causing more contraction.

Proteins on the pull

There are several proteins which interact in muscles:
The two main ones actin and myosin make up 90% of protein in muscles.

Actin

Although actin is a globular protein, it forms a fibrous structure (F-actin) which associates with others to form a double helical structure - rather like strands in rope. It is attached to the Z-discs at the ends of sarcomeres and extends outwards into the cylindrical spaces within them forming 'thin filaments'.
Actin has attachment sites for myosin but these are initially obscured by the protein tropomyosin.

Myosin

Myosin has a distinctive structure with a head, neck and tail. The tails bundle together to form double structures and 'thick filaments', with heads splaying outwards like a bunch of flowers all along the bundled filaments. The head is at an angle so it is sometimes drawn looking like a golf club. At the tip of the head is a binding site can which attach to actin, and it interacts with ATP at a second site to change the angle in the neck region. It can thus be said to have ATPase activity and to act as ATP hydrolase. It moves along the actin fibre by a 'rowing' action. It is attached (via Titin, see below) to the Z-discs at the ends of sarcomeres.

Accessory proteins

Tropomyosin (and troponin) As mentioned above, tropomyosin can associate with actin and prevent access by myosin. This happens when there are no calcium ions present (before/after muscle activity). However in the presence of Ca²⁺ released from the sarcoplasmic reticulum, tropomyosin changes shape (assisted by another protein troponin) and tropomyosin moves out of the way of the binding sites on actin, thus allowing actomyosin crossbridges to form and causing filaments to move relative to one another.

Titin - also known as connectin - is the third most abundant protein in muscle (after myosin and actin). This forms a molecular spring giving 'passive elasticity' to muscle, as a result of the folding of about 33,000 amino acid residues , arranged in 244 protein domains. It runs between the Z-line and M-line, inside the myosin thick filament, so it spans half the length of the sarcomere.

Titin is said to be a giant protein, and it holds a number of records: It is thought to be the largest known protein: over 1 µm in length. Its gene has the largest number of exons in a single gene, as well as the longest single exon.
And its full name - or the concatenation of the amino acid residue names which make its primary structure - has been claimed to be the longest word in English (189,819 letters)!

The M-line is composed of other proteins including Myomesin which anchors the thick myosin filaments to titin filaments.

The Z-line is composed of a protein Alpha-actinin which cross-links with actin and titin.

The processes behind muscle power

Muscles rely on respiration to provide ATP to power the contractions.
Respiration generally uses glucose as a substrate.

Aerobic respiration is much more efficient in producing ATP than anaerobic respiration, but aerobic respiration needs a supply of oxygen, as well as the removal of the waste product carbon dioxide. Glucose and oxygen are supplied to muscles via blood, and carbon dioxide leaves via blood. So the muscles rely on the circulatory system and the respiratory system.
Aerobic respiration involves the processes of glycolysis which occurs in the cytoplasm of cells, and the tricarboxylic acid cycle (Krebs cycle) which occurs in the mitochondria.

Anaerobic respiration also uses glucose as a substrate, but it does not use mitochondria. It also involves glycolysis and the secondary process ('lactic acid fermentation') in the cell's cytoplasm which causes the production of (lactic acid) but not carbon dioxide. Lactate builds up in the cell and then needs to be exported via the bloodstream to the liver for processing (by the 'Cori cycle').

(Under the influence of the hormone insulin) muscles absorb glucose from the bloodstream and store it in the form of glycogen - a polymer of glucose which can be fairly easily broken down to release glucose from the tips of the polysaccharide branches in the active form of glucose 1-phosphate.

In exercise adrenaline stimulates glycogen breakdown via β-adrenergic receptors. The phosphorylated version of the enzyme glycogen phosphorylase catalyzes the conversion of glycogen to glucose 1-phosphate which quickly enters the glycolytic pathway.

An M word

Myo- means muscle

Within the cytoplasm of muscle cells is the protein myoglobin. Like haemoglobin, it reversibly combines with oxygen but it has only one polypeptide chain and a single haem group.

Red blood cells containing oxy-haemoglobin function as a transport system for oxygen, running between the lungs and the respiring tissues.

Myoglobin has a greater affinity for oxygen so it causes oxygen to unload from oxy-haemoglobin and functions as an intracellular oxygen store, close within the muscle fibres. Together with blood capillaries, it tends to give muscles a reddish colour.

Several G words

Glyco- means sugar, and more specifically glucose and its derivatives.
-gen and -genesis mean producer and production
so glycogen produces glucose when broken down
-lysis means the process of breaking down
-neo- means new

Glycogen is a polysaccharide consisting of a variable number of glucose units - up to 30,000.

The process of glycogen synthesis is called glycogenesis. Glucose molecules are added to the free ends of the radiating polysaccharide chains of glycogen for storage.

Glycogenolysis is the breakdown of glycogen, removing glucose units at the tips of polysaccharide branches linked by alpha 1-4 glycosidic bonds and producing glucose 1-phosphate (and a slightly smaller glycogen molecule). This is done by substitution of a phosphoryl group for the α 1-4 linkage.

Gluconeogenesis is the formation of glucose from other (non carbohydrate) compounds, such as glycerol and amino acids, but also pyruvate and lactate formed in different stages of respiration.

In the Cori cycle operating in the liver, lactic acid/lactate is converted into pyruvate and then inefficiently re-formed into glucose by the reverse of glycolysis, at the expense of 4 ATP molecules. The glucose may then be released into the general blood system.

ATP and phosphocreatine in muscle contraction

Creatine is a small molecule, synthesized in the liver and kidneys or taken in from meat products in the diet and it is absorbed and stored in the muscle (and brain tissue).


It can combine with a phosphate group from ATP to form phosphocreatine. This can be seen as a high-energy compound which can be accumulated in the muscle cells, away from the mitochondria in the time before muscular activity.


During muscular contraction, ATP is converted into ADP and Pi, and the chemical energy released is used to power the muscle's contraction. Over time, this ATP can be replaced by ATP coming from respiration.
More importantly, ATP can be quickly regenerated by the reaction of phosphocreatine with ADP, and this ATP formation is independent of the mitochondrial oxidative phosphorylation process.

creatine kinase
phosphocreatine + ADP → creatine + ATP           

The enzyme creatine kinase which catalyses this reaction is bound by the proteins of the M-line, in the centre of the sarcomere

Not to be confused with ..

Creatinine (2-Amino-1-methylimidazol-4-ol) is a substance produced by the breakdown of creatine, and it is a waste product that comes from the 'normal wear and tear' on muscles of the body. It passes fairly continuously into the blood stream.

The efficiency with which the kidneys filter the blood can be measured by the rate at which they remove creatinine from the blood. The rate at which they filter the blood is called the glomerular filtration rate (GFR).

Creatine as a supplement

Used as a nutritional enhancement supplement, creatine is allowed by the National Collegiate Athletic Association and the International Olympic Committee and it is not considered a performance enhancing drug by the World Anti-doping Authority. The use of creatine is found safe and very helpful in increasing capacity during sports activities and high intensity exercise (preferably for athletes over 18 years age). However there have been some concerns about supplement products also containing other (banned) substances.

Slow and fast skeletal muscle fibres

There are two basic different types of skeletal muscle: Slow and fast muscle fibres.

Slow (or type I) muscle fibres - also known as 'slow twitch' muscle fibres because they operate 10-30 times per second - contract slowly, but can keep going for a long time as they are powered by aerobic respiration. Athletes know they are good for endurance activities like long distance running or cycling.
Slow muscle fibres predominate in muscles that are involved in posture as well as prolonged movement, e.g. the soleus muscle in the lower leg.

Fast (or type II) muscle fibres - also known as 'fast twitch' muscle fibres because they operate 30-70 times per second - contract quickly, but rapidly get tired as oxygen cannot be delivered fast enough by the blood flow to meet their needs; they mainly respire anaerobically. They are good for rapid movements like jumping to catch a ball or sprinting.
Fast muscle fibres are found in muscles that are used spasmodically to produce quick movements, such as those controlling eye movements.

It is fairly well known that the speed of muscle fibre contraction is proportional to the ATPase activity of its myosin, and the different forms of myosin predominate in different types of muscle fibres.

Many muscles consist of a mixture of fast and slow muscle fibres. Sometimes athletes have muscle biopsies to use this information to determine their potential for particpation in different sports.

Muscles tend to have specialisations in blood supply and internal chemistry that enable their style of operation.

Feature	Fast muscle fibre	Slow muscle fibre
Type of respiration	Mainly anaerobic	Mainly aerobic
Mitochondria	Low density	High density
Glycogen	High concentration	Low concentration
Creatine phosphate	High concentration	Low concentration
Capillaries	Few	Many
Myoglobin	High concentration	Low concentration

Interestingly birds like pheasants and chickens (bred from jungle fowl) have the two types of muscles in different parts of the body and consequently the meat on the legs is darker (redder) than the white meat on the breast. In these birds the normal method of locomotion is (steady but slow) walking, so the legs have more blood supply, whereas the wings - powered by the breast muscles - are only rarely used for brief bursts of flight activity.