Skeletal Muscle

Skeletal muscles are attached to the bones, are voluntary in nature, and have striations, so they are also called striated muscle. About 40% of the body weight is comprised of skeletal muscle.

Constant little contractions of the skeletal muscle are essential to hold the body upright in any position, even at rest. Skeletal muscles also maintain skeletal stability and protect the skeletal structure from any damage. They act as an external barrier to the body and protect the bones as well as visceral organs from external shock or trauma. They also support the weight of the organs. They also help in the generation of heat by shivering thermogenesis (Fig. 10.2).

10.2.1 Skeletal Muscle: Gross and Microscopic Structure

During embryonic development, embryonic stem cells pro­duce immature muscle cells known as myoblasts (blast = “precursor”) (Fig. 10.3). Later, several myoblasts fuse together to produce one long muscle cell or muscle fiber and so each muscle fiber contains multiple nuclei.

Table 10.1 Comparison between skeletal, cardiac, and smooth muscles

Fig. 10.2 (a) Biceps muscle of horse. (b) Structure of skeletal muscle. Muscle fibers are long cylindrical with multiple nucleuses. Myofibrils are bundles of rodlike contractile elements made up of myofilaments—thick and thin filaments. The muscles are striated due to the regular arrangement of thick and thin filaments

Each muscle fiber is enclosed by a fine layer of loose (areolar) connective tissue called endomysium (“endo”— inside) (Fig. 10.4). Several muscle fibers form a bundle known as fascicles. In fascicles, blood vessels and nerves are present. Fascicles are covered by a connective tissue known as perimysium (“peri”—around). The fascicles are bundled together and form a muscle. The entire muscle is enclosed by a layer of dense fibrous connective tissue called epimysium (“epi”—outside, and “mysium”—muscle).

Different layers of connective tissue extend away from the ends of the muscle fibers themselves and form the tendons or aponeurosis, which connects muscles to bone. Each muscle fiber is covered by its plasma membrane, known as sarcolemma.

The cytoplasm or sarcoplasm contains a huge amount of glycogen (polysaccharide of glucose), which is utilized for energy. Myoglobin, which is a red color pigment, is also present in sarcoplasm. The major portion of the sarcoplasm (almost 80% of the intracellular space) is occupied by myofibrils, which are rodlike cylindrical contractile proteins. Myofibrils run longitudinally. Around 100-1000 myofibrils are present in each muscle fiber. Myofibrils are compactly

Fig. 10.3 Developmentof skeletal muscle fiber. During embryonic stage, a number of uninucleated myoblasts fuse to each other and form multinucleated skeletal muscle cell or muscle fiber. Cells which do not fuse remain as satellite cells and function as muscle stem cells

Fig. 10.4 Cross section of skeletal muscle. Individual fiber is surrounded by endomysium. A number of muscle fibers form a fascicle which is surrounded by perimysium. Several fascicles form a muscle, and the entire muscle is covered by epimysium. All the connective tissue layers of muscle unite at the end and form a tendon, which helps in the attachment of muscle with bone

packed, and the cell organelles remain sandwiched between them. The nuclei get pressed to the periphery of the cell just under the sarcolemma.

10.2.1.1 Description of a Single Muscle Fiber of Skeletal Muscle

An individual muscle cell or muscle fiber has the following parts:

1. Sarcolemma: Sarcolemma is the plasma membrane of individual muscle fiber. Sarcolemma is enclosed by the basement membrane and endomysium (Fig. 10.4). It is an excitable membrane.

2. Sarcoplasm: The cytoplasm in the muscle fiber is known as sarcoplasm. Like that of other cells, different cell organelles are present in the sarcoplasm. Large numbers of glycosomes are present in the sarcoplasm. Small fat droplets and large amount of myoglobin are also present. Myofibrils fill the sarcoplasm. Mitochondria are present in between the myofibrils, near the Z line and A bands.

3. Sarcoplasmic reticulum'. Sarcoplasmic reticulum (SR) is the smooth endoplasmic reticulum (SER) present in the muscle fiber (Fig. 10.5). They form a network of tubes surrounding the myofibrils and remain closely associated with myofibrils. SR stores the Ca²+. During muscle con­traction, this stored Ca²⁺ ions are released out from the SR to the sarcoplasm and reabsorbed during relaxation. The membrane of SR has “pumps” (active transport) for the transport of Ca²+. Along with the “pumps,” the SR mem­brane has special types of openings, or “gates,” for trans­port of Ca²⁺ ions. During relaxation of muscle, these gates remain closed and Ca²⁺ ions are unable to pass through the membrane, and the Ca²⁺ concentration is very high in SR and very low in the sarcoplasm. During muscle contrac­tion, when an impulse reaches the sarcolemma, it propagates through the T-tubule to SR membrane. The action potential initiates the opening of Ca²⁺ “gates” and Ca²+ comes out of the SR into the sarcoplasm.

4. Transverse tubules: Transverse tubules or T-tubules are narrow tubelike structures formed due to invaginations of the sarcolemma (Fig. 10.5). These tubules extend into the interior of the muscle fiber and encircle each myofibril but never open inside the muscle fiber and form sarcotubular system.

Fig. 10.5 Skeletal muscle fiber. (a) Muscle fiber containing sarcoplas­mic reticulum and T-tubules. One T-tubule along with two terminal cisternae forms the triad. (b) Sarcomere of muscle fiber (the sarcomere is the unit of skeletal muscle fiber, which is the length between two consecutive Z-lines). Z-disc or Z-line: It is a line that separates two adjacent sarcomeres; A band: they are dark band known as anisotropic bands or A bands (includes overlapping myosin and actin filaments). I

bands: the area where only actin filaments are present; the light bands are known as isotopic bands or I bands. H zone: a lighter zone in the middle of each dark band or A band (the area where only myosin filaments are present). M-line: a darker line at the middle of each H zone (central line of the sarcomere where myosin filaments are anchored)

3.

Z-disc or Z-lines are fine dense lines that appear in the middle of each I band. Z-line separates two adjacent sarcomeres from each other. In the middle of each dark band or A band, a lighter zone is present known as H zone (H for “helle”—“bright”). Each H zone has a darker line known as M-line (M for “middle”), which runs right down the middle of the A band. Sarcomere of muscle fiber: Sarcomere is the unit of skeletal muscle fiber, which is the length between two consecutive Z-lines. Z-disc or Z-line: It is a line that separates two adjacent sarcomeres; A bands are dark band known as anisotropic bands or A bands (include overlapping myosin and actin filaments). I bands are the area where only actin filaments are present; the light bands are known as isotopic bands or I bands. H zone is a lighter zone in the middle of each dark band or A band (the area where only myosin filaments are present). M-line is a darker line at the middle of each H zone (central line of the sarcomere where myosin filaments are anchored).

4. Myofilaments: Myofilaments are fine stringlike contractile filaments of myofibrils; they consist of thick filament (myosin) and thin filament (actin). Myosin and actin are contractile proteins, which interact with each other to generate force, resulting in shortening of muscle fiber. Two major regulatory proteins troponin and tropomyosin bind to actin and regulate the attachment of myosin head with actin during muscle contraction.

Thick filaments: Thick myofilaments are mainly made up of the protein, myosin (myosin II). Each thick myofilament is approximately 15 nm in diameter composed of about 300 myosin molecules. Each myosin is made up of six protein subunits, two heavy chains and four light chains. The shape of heavy chains is similar to a golf club, with a long shaft-like structure connected to globular myosin head (Fig. 10.6). The heavy chains of myosin are twisted over one another forming a double-helix structure.

The link between the head and the shaft of the myosin molecules remains as a hinge, and so it is known as hinge region. This hinge region is able to bend and gener­ate power stroke during muscle contraction. The centers of the thick filaments are comprised of the shaft portions of the heavy chains. Each head of myosin has two light chains. Each myosin head has a binding site for actin and an ATPase, which hydrolyzes ATP during muscle contraction.

Thin filaments: The thin filaments contain three different proteins, i.e., actin, tropomyosin, and troponin (Fig. 10.7). Each actin molecule has an active site for attachment with myosin head during muscle contraction. Other two proteins, tropomyosin and troponin, are

Fig. 10.6 Thick filament and myosin heavy chain. (a) Half of the myosin molecules have their heads remain towards one end of the thick filament, and the other half remain in the opposite direction. The heads of the myosin bind to the active sites on the actin during muscle contraction. (b) Myosin heavy chain, with a long shaft-like structure connected to globular myosin head. Myosin head has a binding site for actin and an ATPase, which hydrolyzes ATP during muscle contraction

Fig. 10.7 Thin filaments: actin, troponin, and tropomyosin. Strings of globular actin (G-actin) twisted over one another like a double-helical structure. Tropomyosin made up of coiled- coil dimer and the two strands run diametrically opposite to each other along the actin filaments and cover the active sites on actin. Troponin is a complex of three different globular protein subunits, i.e., troponin C, troponin T, and troponin I

regulatory subunits which are bound to actin. Actin is a globular protein called globular actin or G-actin (free monomeric units). Each F-actin (filamentous actin which is the polymer form) is formed by two strings of globular actin (G-actin) twisted over one another like a double­helical structure, which looks like twisting two strands of pearls with each other where individual G-actin molecule is like a pearl necklace. Tropomyosin is another compo­nent of thin filament. It is a long threadlike polypeptide that remains parallel to each F-actin strand and covers the active sites of each G-actin molecule when the muscle remains in relaxed state, whereas during contraction, tropomyosin is replaced from its position and the active site on the actin is exposed to which myosin head binds. Tropomyosin has a structural similarity with that of the myosin tail, being a coiled unit of two protein chains. Tropomyosin made up of coiled-coil dimer and the two strands run diametrically opposite to each other along the actin filaments. Another component of thin filament tro­ponin is a complex of three different globular protein subunits, i.e., troponin C, troponin T, and troponin I.

Troponin C has a receptor for Ca²+ ions and binds to calcium ions (released from the sarcoplasmic reticulum) on activation of the muscle contraction. Another subunit tropo­nin T is the tropomyosin-binding subunit of troponin, which binds with tropomyosin and keeps it in this position on F actin strands. Troponin I binds to actin, holds the troponin­tropomyosin complex in proper position, and inhibits binding of myosin head with actin. It inhibits the interaction between myosin and actin.

During skeletal muscle contraction, Ca²⁺ binds to troponin C, which results in a conformational change in the entire complex, and tropomyosin is released from its position and myosin-binding sites on the G-actin subunits become exposed for attachment with myosin.

Titin or connectin is another important structural protein that functions like a big rubber band in muscles. It is a long elastic protein that runs within the thick filament and extends from the Z-disc to the M. Titin is the third most abundant protein in the muscle after myosin and actin. It is the largest known protein in the body and has around 30,000 amino acids. Titin acts as a molecular spring in the skeletal muscle and prevents overstretching as well as damage of muscle. Titin helps to return the muscle to its normal length when the muscle is stretched.

Dystrophin is another muscle protein, which connects the cytoskeleton of a muscle fiber to the extracellular matrix through the cell membrane. Dystrophin is located between the sarcolemma and the outermost myofilaments. Mutation of the gene coding for dystrophin is one of the major causes of a class of muscle diseases collectively known as muscular dystrophy (MD).

As a complex structure, sarcomere contains a number of proteins; few of them are listed in Table 10.2.

Table 10.2 Different proteins present in the sarcoplasm of vertebrate striated muscles and their properties

(continued)

Table 10.2 (continued)

Source: Craig and Padron (2004)

KEY: CH calponin homology, MD muscular dystrophy, NM nemaline myopathy, FHC familial hypertrophic cardiomyopathy

Fig. 10.8 Neuromuscular junction and acetylcholine receptor channel. (a) Neuromuscular junction and (b) acetylcholine receptor channel: The nicotinic acetylcholine receptor is a ligand-gated ion channel, composed of five subunits arranged symmetrically around a central conducting pore. Upon binding acetylcholine, the channel opens and allows diffusion of sodium (Na⁺) and potassium (K⁺) ions through the conducting pore

10.2.2 NeuromuscularJunction

Nerve impulse or action potential travels through a motor neuron to a skeletal muscle fiber to trigger the contraction of that muscle. The site attachment between the nerve ending and the skeletal muscle is known as neuromuscular junction. It is like that of the synapse between two neurons. This junction is a chemical synapse formed by an axon terminal of the neuron and motor end plate of a skeletal muscle fiber (Fig. 10.8). The motor neuron can have a number of terminal branches; each of these nerve endings attaches with a sepa­rate muscle fiber.

10.2.3 MotorUnit

In the muscle, motor neuron forms many branches and each branch innervates a single muscle fiber. The neuron along with the muscle fiber (innervated by that motor neuron) is known as the motor unit. The size of the motor unit depends on the function of that muscle it innervates. Muscles of limbs and postural muscles are attached with largest motor units, in which one axon supplies many muscle fibers, whereas the smallest motor units, in which one axon may supply only a few muscle fibers, are seen in association with eye movements.

During contraction of a muscle, a number of motor units frequently work together and act like a group and these motor units within a muscle are called motor pool. These muscle fibers within a motor unit are of same type and contract together when activated. The number of motor units also controls the force of contraction.

The terminal branch of the axon does not actually make contact with the muscle fiber but is separated from it by a gap of approximately 50 nm wide called synaptic cleft.

The membrane of nerve terminal releases neurotransmitter (acetylcholine), which has a receptor on postsynaptic mem­brane. The nerve ending has membrane-bound vesicles containing neurotransmitter. These vesicles are synthesized from the cell body of the neuron and come to nerve ending as an empty bag of proteins.

In the nerve endings, the membrane has choline trans­porter, which transports choline from outside of the neuron to inside (Fig. 10.9). Then in the nerve endings, mitochondria synthesize acetyl-CoA, and this acetyl-CoA attaches with choline with the help of the enzyme choline acetyl transferase

and forms acetylcholine. The enzyme choline acetyl transfer­ase is also synthesized from the cell body of the neuron.

Then acetylcholine enters into the synaptic vesicles through the transporter on the membrane of the vesicle and is stored in the synaptic vesicle.

10.2.4 Transmission of Action Potential

Through Neuromuscular Junction

1. Nerve impulses or action potential travels from the brain or spinal cord to initiate the muscle contraction of skele­tal muscle. An action potential propagates through the motor neuron and reaches the axon terminal.

2. During this propagation of action potential through the membranes of nerve endings, the voltage-gated sodium channel opens. This results in the influx of Na²+ inside the nerve endings.

3. As Na²+ enters inside the nerve ending, the charges of the membrane change from the resting membrane potential to depolarization, and it activates the depolarization­sensitive calcium channel. Now voltage-gated calcium channels open and Ca²⁺ diffuses into the terminal.

4. The axon terminal contains membrane-bound synaptic vesicles, which are filled with the neurotransmitter ace­tylcholine (ACh).

Calcium entry causes the synaptic vesicles to release ace­tylcholine neurotransmitter through exocytosis process. The membrane of synaptic vesicles contains a calcium­sensitive protein called synaptobrevin, which is an intrinsic membrane protein of small synaptic vesicles. Synaptobrevin is a specific secretory organelle of neurons, which accumulates neurotransmitters and participates in their calcium-dependent release by exocytosis.

Another calcium-sensitive protein is also present on the membrane of nerve endings called syntaxin (syntaxins are a family of membrane-integrated Q-SNARE proteins participating in exocytosis). As soon as the calcium ions bind with the calcium-sensitive protein, i.e., syntaxin on presynaptic membrane, they transform into active con­figuration and then calcium-sensitive protein on synaptic vesicle, i.e., synaptobrevin attached with it, and a fusion of membrane of synaptic vesicle with the membrane of axon terminal occurs. Then the membrane is dissolved at the site of attachment and results in the release of acetyl­choline in the synaptic cleft through exocytosis.

5. Acetylcholine diffuses across the synaptic cleft and binds to the acetylcholine receptors on the motor end plate, which is a ligand-gated cation channel (Fig. 10.9). Acetylcholine moves from nerve membrane to motor end plate through the synaptic cleft. On the motor end plate, there are receptors (also called nicotinic cholinergic receptor) for acetylcholine attachment (the channel com­posed of pentameric proteins 2 α, β, γ, and δ). There are two attachment sites for acetylcholine on a single channel.

6. ACh binding causes ligand-gated cation channels to open. These ion channels are permeable to both Na⁺ and K⁺.

7. Na⁺ enters the muscle fiber, and K⁺ exits the muscle fiber. More Na⁺ moves inside, and K⁺ goes outside. The greater influx of Na⁺ relative to outward flux of K⁺causes the membrane potential to less negative and the local potential is generated which is also called motor end plate potential.

8. Then the entry of more number of Na⁺ ions changes the end plate potential to threshold potential.

Then this threshold potential causes opening of voltage­gated Na channel nearer to motor end plate. Then more number of Na⁺ ions enter inside the cell through the voltage-gated Na⁺ channel, and as a result, an action potential generation occurs which propagates along the sarcolemma.

9. The action potential travels across the sarcolemma and is propagated down the T-tubules. The T-tubules are filled with extracellular fluid, high in sodium (Na⁺) and low in potassium (K⁺) ions.

10. Before the discussion of spreading of action potential and starting of muscle contraction, let us describe how the stimulation of the ACh receptors is terminated.

For relaxation of muscle, ACh should be removed from the synaptic cleft. It is initiated when ACh is cleaved (split) by an enzyme called acetylcholinesterase, which remains in the synaptic cleft. Acetylcholinesterase splits ACh into acetate (acetyl) and choline.

The acetate diffuses out of the synaptic cleft and choline, which is an essential nutrient in the vitamin B group (B4), and is taken up by the axon terminal, where it is recycled to make more acetylcholine.

10.2.5 MuscleContraction

A series of molecular events occur during muscle contraction known as the crossbridge cycle. The following steps occur during contraction (Fig. 10.10).

10.2.5.1 Crossbridge Formation

The action potential spreads through the sarcolemma, and it reaches the T-tubules. The action potential triggers SR. The resultant change in potential causes the voltage-gated channels in the T-tubule to respond. In the T-tubule, these channels are known as dihydropyridine channels (DHP) or L-type Ca²+ channels. They are mechanically linked to ryanodine receptor channels (RyR), which are calcium channels located in the membrane of sarcoplasmic reticulum. When the membrane potential changes, then the DHP chan­nel opens and Ca²⁺ ions come out of the sarcoplasmic reticu­lum and diffuse into the sarcoplasm. Then Ca²⁺ ions bind to the troponin C. The binding of Ca²⁺ ions causes conforma­tional change in troponin. Then tropomyosin which covers the active site of the actin moves from its position, which results in the exposure of active site of G-actin molecule.

Now myosin head attaches with the binding site on G-actin molecule and the formation of crossbridges occurs.

10.2.5.2 Power Stroke Generation

When muscle remains in relaxed state, the myosin head is “cocked.” ADP and phosphate (Pi) remain attached with myosin head. As the myosin head is attached with actin, the Pi detaches from the myosin head and energy is released. This energy results in bending of myosin head. The bending or power stroke forcefully pulls the actin past the myosin. ADP is also released from the myosin during the power stroke. Myosin heads pull the thin filament towards the middle and sarcomere shortens.

10.2.5.3 Crossbridge Detachment

For considerable shortening of muscle fiber, the myosin heads must be detached from the actin and reattached with the next actin molecule. When another ATP attaches with myosin head, the attachment of myosin head with actin becomes weaker and myosin head detaches.

10.2.5.4 Reactivation of Myosin Heads

The ATPase present in the myosin heads hydrolyzes the ATP into ADP and Pi, which causes the head to “recock” (the recovery stroke), preparing it for the next power stroke.

The hydrolysis of ATP releases energy which re-energizes the myosin head for the next power stroke. During muscle contraction, each myosin molecule undergoes the entire crossbridge cycle numerous times, so the process is known as crossbridge cycling. The crossbridge cycle will repeat as long as the active site in actin is exposed. As the cycle repeats, the sliding of thin filaments over the thick filaments occurs and Z-lines come closer, resulting in shortening of sarcomere. This shortening causes the whole muscle to contract. As long as Ca²+ is present and the active sites are exposed, the process will continue.

Fig. 10.10 Pathway of skeletal muscle contraction. (1) The active site on the actin is exposed as Ca ions bind to troponin. (2) The myosin head forms a crossbridge with actin. (3) During the power stroke, the myosin head bends, and ADP and phosphate are released. (4) A new molecule of ATP attaches to the myosin head, causing the crossbridge to detach. (5) ATP hydrolyzes to ADP and phosphate, which returns the myosin to the “cocked” position

10.2.6 MuscleRelaxation

During relaxation of muscle, the release of neurotransmitter (acetylcholine) stops. The remaining acetylcholine is broken down into acetate and choline by acetylcholinesterase. This stops the release of Ca²⁺ from the sarcoplasmic reticulum (SR). Then Ca²⁺ ions diffuse away from troponin C and are pumped back into sarcoplasmic reticulum (SR) by the ATP-dependent Ca²⁺ pump in SR membrane.

Tropomyosin returns back to its original position and covers the active site on the individual G-actin molecules. This prevents crossbridges from reforming. A new ATP binds to the myosin head. Binding of actin and myosin stops, and relaxation of muscle fiber takes place.

Know More.......

The sliding filament model of muscle contraction explains the fact that when skeletal muscle fibers con­tract, the individual proteins (actin and myosin) do not shorten. Rather, they slide over each other. ATP is necessary for detachment of myosin heads from actin. Also it is interesting that when a sarcomere contracts, both the H zone and the light I band shrink in width, while the dark A band does not appear to narrow.

10.2.7 MuscleTone

Muscle always maintains a tension or resistance to stretch (Fig. 10.11). This tension or resistance to stretch is called muscle tone. Skeletal muscles are seldom completely relaxed, or flaccid, even at that time of rest when a muscle does not produce any movement. During rest, little contraction is present in the muscle fibers, which are essential for maintaining the posture, balance of the body, generating the reflexes, and controlling functions of different organs. Mus­cle tone is also seen in cardiac and smooth muscles. A complex interaction of nervous system and muscles is required for the activation of a few motor units at a time.

That is why muscles not at all fatigue completely because some motor units can recover from fatigue when others are active. The absence of the skeletal muscle tone results in the absence of low-level contractions that lead to loss of resistance to passive stretching muscle. This type of muscle tone is called hypotonia. Hypertonia occurs due to any dam­age of central nervous system (CNS), such as the cerebellum, or due to loss of innervations to the skeletal muscle. Hypo­tonic muscles show a flaccid appearance and exhibit func­tional impairments, such as weak reflexes.

Excessive muscle tone is called hypertonia, which results in hyperreflexia (excessive reflex responses). Hypertonia often occurs due to the damage of upper motor neurons in the CNS. Hypertonia is seen in muscle rigidity or spasticity. This type of condition is seen in neurological disorders in the body like Parkinson’s disease.

10.2.8 TypesofMuscleContraction

Force (tension) and length (shortening) are two important variables for description of skeletal muscle contraction. The force which is exerted by a muscle on an object during contraction is known as muscle tension, whereas the force that is exerted by an object to a muscle is known as load (weight of the object). On the basis of the force of contraction and change of muscle length, muscle contractions are of two types.

10.2.8.1 IsometricContraction

When the tension of muscle increases but the length of the muscle remains the same, then the contraction is known as an isometric contraction (iso = same, metric = length). In this type of contraction, muscle provides force but no movement occurs at the joint and muscle length remains unchanged. Isometric contractions of muscles are very important for maintaining posture or stabilizing a joint. Examples of activities where muscles use isometric contraction include pushing an object that was initially stationary or holding a weight in a certain place above the ground.

10.2.8.2 Isotonic Contraction

When the muscle length changes but the muscle tension remains unchanged, then the contraction is known as an isotonic contraction (tonic = tension). Isotonic contraction is seen during walking, running, and different types of activities.

Based on the pattern of muscle length changes, the iso­tonic contraction is classified into concentric and eccentric contractions.

If the entire muscle shortens during contraction, then it is called concentric contraction. For example, during lifting a weight, the concentric contraction of the biceps muscle causes the arm to bend at the elbow and lifting the weight towards the shoulder.

If the total length of a muscle increases when tension is produced, then the contraction is called eccentric contraction.

Fig. 10.11 Multiple motor unit recruitment and stimulus intensity. Stimulating the whole nerve with higher and higher voltage produces stronger contractions. More motor units are being recruited called multiple motor unit summation

For example, the lowering phase of a biceps curl shows an eccentric contraction. In eccentric contraction, muscles are able to generate greater forces than in isometric or concentric contractions.

10.2.9 MuscleTwitch

Muscle contraction due to a single action potential is known as twitch contraction (Fig. 10.12). When a single action potential travels through the motor neuron and reaches the muscle fiber of that unit, it initiates the contraction of that single muscle fiber. This isolated contraction is known as muscle twitch. The duration of muscle twitch depends on the type of the muscle, and it can last for a few milliseconds to 100 ms.

Myogram is the graphical representation of the phenom­ena of muscular contractions (Fig. 10.13). A single muscle twitch has three phases, i.e., latent period or lag phase, contraction phase, and relaxation phase. The first phase is called latent period or lag phase (1-2 ms), which is the short time between the application of stimulus and starting of muscle contraction. During this period, propagation of action potential in the sarcolemma occurs and Ca²⁺ ions are released from the SR for binding with the troponin C. Then tropomy­osin moves from its position, myosin head is attached with the actin, crossbridges are formed, and as a result shortening of the muscle fiber occurs. The last phase of twitch is the relaxation phase.

During relaxation phase, muscle contraction stops, Ca²⁺ ions are pumped back to the SR by calcium pump, and muscle returns back to its original resting length. The

Fig. 10.12 A myogram of a muscle twitch. A single muscle twitch has three phases, i.e., a latent period between the point of stimulus and the starting of contraction, a contraction phase when tension increases, and a relaxation phase when tension decreases

duration of twitch varies between different types of muscle and ranges from 10 to 100 ms.

The refractory period is the time immediately after appli­cation of a stimulus. If a stimulus is applied during the contraction stage of the muscle, then muscle will not respond to this second stimulus.

10.2.9.1 Factors Influencing Force of Muscle Contraction

Based on the type of work, muscles can generate different levels of force during contraction. Some actions need much more force generation, whereas some work requires less force like lifting a heavy load requires more force compared to lifting a light object.

10.2.10 Multiple Motor Unit Summation or Recruitment

Different ranges of motor units are prudent in a skeletal muscle, and nervous system has a wide range of control over the muscle (Fig. 10.13). Small motor units are innervated by smaller motor neurons with lower threshold. These motor units generate relatively small degree of con­tractile strength (tension).

Larger motor units are also present with bigger motor neurons having higher threshold. These neurons activate larger muscle fibers and are used when more strength is required. So, increased activation of motor units results in increase in muscle contraction, which is known as recruit­ment. Motor unit summation is the recruitment of extra motor units within a muscle to develop additional force. The summation of motor units occurs until sufficient force is developed by recruitment of more numbers of motor units within that muscle to move a load. The maximum contraction is generated when all the motor units within a muscle are activated.

The muscle contraction becomes progressively stronger due to recruitment of more number of muscle fibers. In some skeletal muscles, the largest motor units can generate a con­tractile force of 50 times greater than the smallest motor units in that muscle. The greater the load an animal is carrying, the more number of motor units are activated.

However, at the time of generation of the maximum force, animals are only able to use about 1/3 of total motor units at one time. All muscle fibers do not fire at the same time, which helps in the generation of maximum force and prevents the muscles from fatigue. When muscle fibers begin to fatigue, they are replaced by other fibers, resulting in maintenance of the force. However, under extreme conditions, animals are able to recruit even more motor units at a time to perform a heavy work.

10.2.10.1 WaveSummation

In a muscle fiber, the tension depends on the rate of firing action potential by a motor neuron to that muscle. If the muscle is stimulated before the end of previous twitch, the second twitch will be stronger, and this phenomenon is called wave summation (Fig. 10.14). Wave summation occurs when a given set of muscle fibers is stimulated repeatedly without complete relaxation. The second stimulus causes the release of more number of Ca²+ ions from the SR. These Ca²+ ions are utilized for the activation of additional sarcomeres while

Fig. 10.13 Multiple motor unit summation or recruitment. (a) Twitch contraction, (b) wave summation, (c) treppe, (d) incomplete tetanus, (e) complete tetanus

the muscle is still contracting from the first stimulus. So, summation results in greater contraction of the motor unit.

10.2.10.2 Treppe

When a muscle is stimulated with repeated stimuli and the stimuli are given just after the completion of the previous contraction, then the tension of the muscle increases in a graded manner till a maximum height is reached, which looks like a staircase (Fig. 10.14). This phenomenon is known as treppe or staircase effect. The frequency of stimuli should be just below the tetanizing frequency.

In this condition, due to a steady stream of signals from the motor neuron, the concentration of Ca²+ ions in the sarcoplasm becomes very high.

10.2.10.3 IncompleteTetanus

If a muscle is given repeated stimuli during contraction phase, then the contraction mechanism will start repeatedly before any relaxation has occurred. Increasing the frequency of motor neuron signaling increases summation, and tension in the motor unit keeps on rising until it reaches a peak. The tension at this time is several times more than the tension of a

Fig. 10.14 A schematic depicting the sarcomere length­tension relationship

single muscle twitch. This state of muscle is called incom­plete or unfused tetanus. During incomplete or unfused teta­nus, the muscle goes through quick cycles of contraction with a short relaxation phase for each contraction.

Incomplete tetanus occurs due to repeated stimulus, when there are phases of incomplete relaxation between the summated stimuli (Fig. 10.14).

10.2.10.4 Complete Tetanus

If the frequency of the stimuli is very high and the muscle will not get time for relaxation, then the phenomenon is called complete tetanus (Fig. 10.14). In complete tetanus, the relaxation phases are absent and the contractions become continuous. In complete tetanus, the individual responses fuse and form one continuous contraction. Tetany is the sustained contraction resulting from high-frequency stimulation.

During tetanus, the concentration of Ca²+ ion remains very high in the sarcoplasm and that allows nearly all of the sarcomeres to form crossbridges and shorten, and the con­traction continues uninterrupted (until the muscle becomes fatigue and is not able to produce tension).

10.2.11 Length-Tension and Force-Velocity Relationship

10.2.11.1 Sarcomere Length-Tension Relationship

A direct relationship is there between the initial length of muscle fibers and the tension in the muscle or force of contraction.

The initial length of the sarcomere influences the force of the contraction, which a muscle can generate (Fig. 10.14). If the sarcomere length is optimum, the isometric tension is maximum due to the position of thin and thick filaments forming maximum number of crossbridges in sarcomere. If the initial sarcomere length is very short, then the thick filaments will already be pushing up against the Z-disc. In this situation, there is no chance of further shortening of the sarcomere as the latter is already short and muscle will not be able to generate much force.

Similarly, if the muscle is stretched very high, then the myosin heads can no longer be able to contact the actin and less force will be generated.

So, maximum force is produced if the muscle is stretched to the point which allows every myosin head to contact with the actin and when the sarcomere has the maximum distance to shorten, i.e., the thick filaments are at the very ends of the thin filaments. This is applicable only in isometric contrac­tion. During dynamic contraction, length-tension relationship must be combined with force-velocity relationship to deter­mine the effect that both length and velocity have on muscle tension.

10.2.11.1.1 Application of Length-Tension Relationship

When applying to muscle joint system, sarcomere length is not same throughout. So, at a particular joint position, there are sarcomeres at many different lengths corresponding to different points of length-tension relationship. During move­ment, torque produced at joint is not only due to muscle force but also due to function of moment arm (MA) of muscle. So,

Fig. 10.15 A schematic depicting muscle force-velocity curve

at particular joint position, muscle length may be short but has long MA, maintaining higher torque.

10.2.11.2 Force-Velocity Relationship

The speed of shortening of myofilaments also affects the tension development. Speed of shortening depends on the type and length of muscle fiber. Force-velocity relationship describes the relation between the velocity of muscle contrac­tion and the force produced (concentric and eccentric muscle contraction) (Fig. 10.15). The force which is generated dur­ing muscle contraction is the function of velocity of contraction.

For example, in concentric contraction, if speed decreases, the tension increases.

In isometric contraction, the shortening speed is 0, but the tension reduced is more than concentric contraction. In eccentric contraction, as the lengthening speed increases, the tension increases and then plateaus.

10.2.12 SkeletalMuscleEnergetics

and Metabolism

Muscle contractions require plenty of energy. The major portion of this energy is utilized for the crossbridge cycles, and some portion is also utilized for propelling the Ca²+ ions back into the SR from the sarcoplasm during relaxation of the muscle and propelling Na⁺ and K⁺ ions through the sarcolemma.

ATP is the instant source of energy (ATP → ADP + Pi + energy) for muscle contraction. Contin­uous supply of ATP is required for muscle contraction. For muscle contractions, there are four different ways through which muscles get the ATP.

1. Cytosolic stored ATP: Very little amount of ATP remains inside the muscle fiber as stored ATP. This cytosolic stored ATP can instantly provide energy for contraction and does not require oxygen. Very little amount of ATP is stored in muscle fibers, which can provide energy for muscle contraction for a few seconds. So, it is not enough for long-term contraction. This cytosolic ATP provides energy for contraction of eye muscles which contract constantly and quickly but for a very little period.

2. Creatine phosphate: Muscles cannot obtain ATP from the blood or other tissues. They can produce it as per need. ADP (2 molecule), inorganic phosphate (Pi), and energy from other chemical sources are required to generate a single molecule of ATP by rephosphorylation of ADP. When the cytosolic stores of ATP are utilized, muscle fiber initiates another rapid energy source, i.e., creatine phosphate (CP). Creatine phosphate is a high-energy com­pound, which can rapidly transfer its phosphate to an ADP molecule for synthesis of one molecule of ATP (Fig. 10.16). The process is called phosphagen system, and it does not require oxygen. Creatine kinase or creatine phosphokinase (CPK) enzyme catalyzes the reaction. Cre­atine kinase enzyme is present on the M-line of the muscle fiber.

But the energy available from the stored creatine phos­phate is also limited, which is sufficient for another 5-8 s. This source is also termed as the immediate energy source and is a very important source of energy for activities like jumping, hitting, and throwing.

Fig. 10.16 Sources of energy for muscle contraction. (a) Molecular pathway of creatine phosphate synthesis. At the time of muscle contrac­tion when muscles require ATP, the reaction is represented by the above equation that runs from left to right. When the muscle is at rest and

excess ATP is available, the reaction is represented by the above equation that proceeds from right to left. (b) Glycolysis pathway. (c) Anaerobic mechanism (glycolysis and lactic acid formation). (d) Aero­bic or oxidative respiration

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Creatine phosphate or phosphagen system is rapidly replenished during recovery. It requires about 30 s to replenish about 70% of the phosphagens and 3-5 min to replenish 100%. During intermittent work (short periods of activity followed by rest periods), much of the phosphagen can be replenished during the recovery period and thus be used over and over again.

3. Glycolysis: Glycolysis is the metabolic pathway which breaks down glucose into pyruvate and a hydrogen ion (H⁺). Glucose molecules reach the muscle tissues through blood. Glucose is also produced in muscle cells through breakdown of stored glycogen (Fig. 10.16). The glycolysis in skeletal muscle generates ATP molecules required for contraction. Glycolysis which occurs in the absence of oxygen is called anaerobic glycolysis, which is the main source of ATP during anaerobic activity. Glycolysis process is very fast and can supply energy for intensive muscular activity, but it can supply energy for about a minute before the muscles begin to fatigue. Glycolysis occurs in the cell cytosol and can produce molecules 2 ATP by converting a glucose molecule into pyruvate. In anaerobic glycolysis, the pyruvic acid is converted to lactic acid. The accumulation of lactic acid reduces the pH and makes it more acidic, which produces the stinging feeling in muscles during exercise. This slows down further anaerobic respiration and brings fatigue. Now when the activity of the muscle slows down, oxygen becomes available and lactate is converted back into pyruvate.

4. Aerobic or oxidative respiration: The different mechanisms discussed above are able to supply ATP for about a minute.

But the different activities like walking and running which continue for a long duration require a constant supply of ATP. So, in these activities where constant ATP is required, the cells utilize aerobic or oxidative respiration occurring in the mitochondria (Fig. 10.16). This aerobic respiration can supply adequate ATP to the muscle cells for hours, but this process of metabolism is slower than anaerobic mechanisms and is not fast enough for intense activity.

It is an important source of energy for muscle contractions of athlete animal and for endurance exercise required of migrating animals, where repetitive skeletal muscle contractions continue for hours or days. Though glucose can be used as an energy source for aerobic respiration, the primary fuel for muscle contractions dur­ing prolonged endurance exercise is fatty acids rather than glucose. These fatty acids are broken down to acetyl-CoA and enter the citric acid cycle and produce ATP.

Muscle contractions are 50-70% efficient in regard to completion of a work, and the nonwork portion is dissipated as heat. This heat source is very important for the mainte­nance of body temperature. During cold stress, shivering results in the production of heat in the body.

10.2.13 MuscleFatigue

If a muscle is used exhaustively, then the performance of the muscle decreases progressively, which mostly recovers after a period of rest. This phenomenon is known as muscle fatigue. This process is temporary and reversible state of muscle. When a muscle is contracted for a long time, then muscle fatigue occurs. If fatigue starts in a muscle, then the force of the muscle decreases and the response of that muscle to stimuli reduces and as a result the activity levels decrease. In fatigue condition, the muscle is unable to contract opti­mally. Muscle fatigue starts at the time of heavy muscular activity or exercise. As the muscle starts fatigue, the speed and force of contraction reduce, relaxation time prolongs, and a period of rest is required to restore normal function. The factors which influence the muscle fatigue are the following:

10.2.13.1 Effects of Muscle Fatigue

Muscle fatigue causes different types of sign and symptoms in the body like muscle pain, burning, fast breathing, vomiting, and stomach pain.

10.2.13.2 Types of Muscle Fatigue

There are two types of fatigue, i.e., central fatigue and peripheral fatigue:

Central fatigue—It occurs due to the decrease in the capac­ity to voluntarily activate a muscle during a maximal effort. It occurs due to a decrease in motor unit recruitment levels or a reduction in motor unit firing rates or both.

Peripheral fatigue—It occurs due to the decrease in the capacity of a muscle to produce force even if it is receiving signals from the nervous system.

10.2.14 Types of Skeletal Muscle Fiber

Skeletal muscle fibers can broadly be classified into type I or slow-twitch fibers and type II or fast-twitch fibers on the basis of their contraction speed and fatigue resistance. The relative proportions of these types of muscle fibers are basically determined by genetic factors and influenced by physiologi­cal, hormonal, and nutritional factors.

1. Slow-twitch muscle fibers: The slow-twitch muscle fibers are also known as type I muscle fibers. They have myoglo­bin content and are red in color. Their contraction speed is less than the other types of muscle fibers. The muscle fibers are smaller and produce tension slowly. Their capacity to produce force or power is less. But the main advantage is that these types of muscle fibers are slow to fatigue. They have high myosin ATPase activities, capillary density, and mitochondrial density and have low power. Slow-twitch fibers depend on oxygen for energy, and they can continue the activity for long duration. These types of muscle fibers are generally associated with endurance activities, and highly active animals or athlete animals have higher propor­tion of these types of muscle fibers in the body.

2. Fast-twitch muscle fibers: Fast-twitch muscle fibers are also known as type II muscle fibers. The speed of contrac­tion is faster than the type I muscle fibers. The duration of contraction is short. Type II muscle fibers are more pow­erful than type I muscle fibers and are associated with activities such as lifting a heavy weight, which requires more power. This type of fibers gives major strength to the animal, but they become fatigue very quickly. These fast­twitch fibers can be further classified into fast-twitch oxi­dative-glycolytic fibers (type IIa) and fast-twitch glyco­lytic fibers (type IIb) in rodents and pigs. In large mammals including humans and ruminants, type IIx replaces type IIb as the dominant fast-twitch fibers.

Type IIa muscle fibers—Type IIa muscle fibers depend on oxidative glycolysis for energy and produce lactic acid. But the duration of contraction is very short. Animals that are associated with powerful activities have higher proportions of type IIa fibers in their muscles.

Fast-twitch glycolytic (type IIx) fibers—Type IIx muscle fibers are faster and more powerful than type IIa muscle fibers. They also fatigue very quickly. They are associated with the activities of very short duration and which require more power.

In cheetahs and domestic cats, several muscles have high proportion of type IIx fibers and low proportion of type I fibers. In beagle dogs, the percentage of type IIa fibers is very high (Table 10.3).

10.2.15 RigorMortis

The word rigor mortis came from two Latin wards, i.e., “rigor” means “stiffness” and “mortis” means “of death.” Rigor mortis or postmortem rigidity of muscles is an impor­tant sign of death of an animal. It starts a few hours after death. After death of the animal, the muscles become rigid, it is difficult to move or manipulate the body, and the state is irreversible. In the muscle, continuous actin-myosin interac­tion is seen in rigor mortis. After death of the animal, cellular respiration stops and results in stop of synthesis of adenosine triphosphate (ATP). So, ATP is not available for relaxation of muscle and muscle remains in contraction state.

10.2.15.1 MechanismofRigorMortis

1. Absence of ATP → no reuptake of Ca²+ into the SR as Ca²⁺ uptake also requires ATP-dependent Ca²⁺ pump → Ca²+ level of sarcoplasm ↑ → continued binding of Ca²+ to troponin C → abnormal, rigid, and uninter­rupted contraction.

2. No ATP → no relaxation, a new molecule of ATP must attach to the myosin head for detachment of actin-myosin interaction → thus, when no ATP is present, then myosin heads cannot detach themselves from actin.

In humans, rigor mortis starts after about 3-4 h after death. It reaches maximum stiffness after about 12 h and gradually dissipates until approximately 48-60 h (3 days) after death. The onset of rigor mortis depends on the ambient tempera­ture. The warm conditions can speed up the process of rigor mortis. Rigor mortis ends when contractile proteins of the muscle like other body tissues undergo autolysis caused by enzymes released by lysosomes.

10.2.15.2 Factors Affecting Rigor Mortis

Ambient temperature: Cold temperature inhibits rigor mortis and the onset of rigor becomes slower, whereas hot temperature accelerates the process and faster onset and faster progression of rigor mortis occur.

Activity before death: Anaerobic exercise before death accelerates the rigor mortis process because lack of oxy­gen to muscle buildup of lactic acid and higher body temperature accelerate rigor. Sleep before death slows the process as fully oxygenated muscles exhibit rigor more slowly.

Body mass: In obese animals, the rigor mortis process is slow because fats store oxygen. In thin animals, the process is fast as the body loses oxygen quickly.

Table 10.3 Comparison between three types of muscle fibers

10.3