Muscles are the cells that dominate force. They allow us to move as well as exercise. There are three types of muscle. 

These types are skeletal muscle, smooth muscle, and cardiac muscle. Most skeletal muscle involves an attachment to a bone and follows muscle support (1).

Smooth muscle has origins in organs, stomach, intestines, urinary bladder, uterus, blood vessels, and airways in the lungs  (1).

Smooth muscle cells help with our body’s intricate details, including pulse change from our eyes, regulating digestion, and allowing the skin’s hair to stand up when cold  (1).

Cardiac muscle is a muscle relating to the heart that involves the heart’s contraction and regulating blood pressure throughout the circulatory system  (1).

Structure

Skeletal muscle has a series of alternating light and dark bands. These bands lie perpendicular to the long axis and are striated (1).

Cardiac muscle is also striated, showing these alternating light and dark bands perpendicular to the long axis (1).

Smooth muscle lacks a striated appearance. 

Cellular structure

Muscle fiber fills with mononucleated cells known as myoblasts into a single, cylindrical, multinucleated cell  (1).

Satellite cells are cells that help with a repair process that incorporates undifferentiated stem cells. Satellite cells activate when there is strain or injury. These cells will undergo mitotic proliferation. These cells will also differentiate into myoblasts and fuse together to form new fibers to repair the cells (1).

Connective Tissue Structure

Muscle is related to skeletal muscle; muscle binds to connective tissue and consists of collagen fibers. These collagen fibers are known as tendons (1).

Filament Structure

Myofibrils are cylindrical bundles. 

Thick filaments have protein myosin. Myosin has polypeptide heavy chains and four smaller light chains  (1).

Cross-bridges consist of myosin molecules along the thick filament and have two globular heads that extend out to the sides (1).

Myosin-ATPase hydrolyzes the bound ATP and harnesses energy for contraction. Myosin-ATPase is an enzyme related to energy (1).

Myosin cross-bridges contain light chains, ATP binding sites, and actin-binding sites. Therefore thick filaments have cross-bridges, while thin filaments have proteins that include tropomyosin, actin, and troponin (1).

Actin is a protein called nebulin. Nebulin plays a role in the assembly of different proteins. Troponin and tropomyosin are involved in the contraction of muscle fibers on actin (1). 

Sarcomere Structure

The sarcomere is a structure in which there are repeating patterns of thick and thin filaments. The filaments involve thick filaments in the middle of each sarcomere (1).

The A band is a wide, dark band in the middle of each sarcomere (1).

Z lines are thin filaments at the end of each filament. These proteins are interconnecting and overlap a portion of thick filaments (1).

The I band is a light band and is between the ends of the A bands of two adjacent sarcomeres that contain portions of thin filaments. These filaments do not overlap the thick filaments. The Z line also bisects the I band (1).

H zone is a narrow, light band. This band is the center of the A-band (1).

M line is a narrow, dark band in the middle of the H zone. This zone represents proteins that link together with adjacent thick filaments (1).

Titin, are filaments that consist of elastin. These proteins extend from the Z line to the M line and link to the M-line proteins and thick filaments. The M line works to connect the thick filaments with the titin filaments. This connection helps to maintain the alignment of filaments in the middle of each sarcomere (1).

A muscle fiber is a single muscle cell in the connective tissue in the muscle (1).

A myofibril is a portion of muscle fiber. Myofibrils consist of A bands, I bands, and two Z lines. Z line to Z line is a sarcomere. The sarcomere consists of two Z lines from end to end, and the M line is the protein in the middle of the sarcomere, where the H zone covers the M line. Thin actin filaments comprise thick myosin filaments (1).

Myofibril Structures

The sarcoplasmic reticulum involves muscle fiber. 

Terminal cisternae have regions that connect to smaller tubular elements  (1).

Calsequestrin is a protein that binds calcium and allows the storage of calcium (1).

Transverse Tubules or T-tubules are between the terminal cisternae and the sarcoplasmic reticulum (1).

These tubules surround the myofibrils at the sarcomeres, where A and I bands meet (1).

The plasma membrane is continuous with T-tubules and allows action potentials to propagate along the surface membrane through the muscle fiber’s interior through the T-tubules (1).

The plasma membrane is also known as the sarcolemma. 

Contraction is related to the activation of muscle fibers generating force through cross-bridges (1).

After the force generation,  the muscle tension relaxes (1).

Membrane Excitation: The Neuromuscular Junction

Alpha motor neurons are neurons whose axons innervate skeletal muscle fibers. These cell bodies exist in the brainstem and the spinal cord (1).

Motor neurons are myelinated, which helps the transmission of action potentials. These action potentials propagate at high velocities and allow minimal delay when contracting muscle fibers for contraction (1).

Motor neurons, combined with muscle fibers, are termed motor units (1).

Some neurotransmitters package themselves within vesicles at axon terminals and allow synaptic transmission between the neurons. These neurotransmitters are acetylcholine (ACh) (1).

The motor end plate is an axon under the terminal portion of the plasma membrane (1).

Events of an action potential

1. Action potential in a motor neuron arrives at the axon terminal.
2. The action potential depolarizes the plasma membrane.
3. Then the action potential at the T-tubule opens voltage-sensitive Ca2+ channels.
4. The Ca2+ channels allow calcium ions to diffuse into the axon terminal from the extracellular fluid.
5. The Ca2+ binds to proteins and enables ACh-containing vesicles to fuse with the neuronal plasma membrane.
6. ACh releases into the extracellular cleft and separates the axon terminal and motor end plate.
7. ACh diffuses from the axon terminal to the motor end plate.
8. The ACh binds to the ionotropic receptors of the nicotinic type.
9. The binding of ACh opens the ion channel while sodium and potassium pass through the channels.
10. End plate potential moves sodium in while potassium is out, and there is a local depolarization of the motor end plate. EPP is analogous to an EPSP (excitatory postsynaptic potential). 

EPP is larger than EPSP since the neurotransmitters extend over a larger surface area, allowing more ion channels to be open  (1).

EPP can, therefore, depolarize the entire membrane  (1).

Action potentials in motor neurons will always produce contraction in a motor unit  (1).

This contraction is different from neurons needing EPSPs to reach a certain threshold  (1).

Another critical difference between muscle cells and healthy cells is that they do not form inhibitory potentials or IPSPs to inhibit action potentials. In skeletal muscle, neuromuscular synapses are excitatory every time (1).

The synaptic junction contains the enzyme acetylcholinesterase. Acetylcholinesterase breaks down ACh. Choline is transported back into the axon terminals and reused to synthesize new ACh (1).

When ACh decreases in the synaptic cleft, there is less available neurotransmitter to bind to the receptors. Once there is no more ACh, ion channels close (1).

Disruption of Neuromuscular Signaling

Curare is a deadly poison that binds firmly to nicotinic ACh receptors. This reaction means that ACh cannot link to the receptor, therefore preventing contraction (1).

Nerve gases inhibit acetylcholinesterase. This reaction allows the poison for chemical warfare use. The loss of receptor responsiveness to ACh causes paralysis or death from asphyxiation (1).

Pralidoxime is a drug that reactivates acetylcholinesterase.

Atropine is a muscarinic receptor antagonist that does the same thing and reactivates acetylcholinesterase (1).

Succinylcholine acts as an agonist to the ACh receptors and produces a depolarizing block. This reaction is similar to acetylcholinesterase inhibitors (1).

Rocuronium and vecuronium are drugs that act like curare and acetylcholinesterase. These are used in the surgical field to prevent muscular contractions  (1).

Clostridium botulinum is a toxin that blocks acetylcholine release from axon terminals (1).

Botulinum toxin is an enzyme that uses the process of blocking acetylcholine. The toxin breaks down the proteins of the SNARE complex. The SNARE complex is required to bind and fuse ACh vesicles with the axon terminal’s plasma membrane (1).

Botulism is the poisoning from food, but this toxin can block ACh release at neuromuscular junctions and help with cosmetic procedures (1).

Excitation-Contraction Coupling

Excitation-contraction is the sequence of events by an action potential to activate the force-generating mechanisms (1).

The function of Ca2+ in Cross-Bridge Formation

Calcium initiates force generation by troponin and tropomyosin (1).

Tropomyosin is a molecule that contains seven actin monomers. These tropomyosin molecules arrange along the thin actin filament (1).

The molecules cover the myosin-binding site and are on each actin moner. These proteins prevent the cross-bridges from making contact with actin (1). 

The tropomyosin holds together by a smaller protein called troponin (1).

Troponin is the protein that interacts with actin and tropomyosin (1).

There are three subunits. I, T, and C

I is inhibitory, T is tropomyosin-binding, and C is related to the calcium-binding process (1).

One molecule of troponin binds to each unit of tropomyosin. This binding allows access to myosin-binding sites on the seven actin monomers to interact with tropomyosin (1).

When cross-bridges occur, tropomyosin moves away from the actin and allows calcium to bind to the troponin C (Ca2+ binding) site (1).

When calcium binds to troponin C, it produces a change in the troponin, relaxes the grip, and allows tropomyosin to move away from the myosin-binding site on each actin molecule (1).

The removal of calcium turns off contractile activity.

Cytosolic calcium determines the number of troponin sites occupied by calcium, identifying the number of actin sites available for cross-bridge binding (1).

Thus, when there is an action potential, there is a rapid increase in cytosolic calcium concentration. Calcium binds to troponin, removes tropomyosin’s blocking effect, and allows myosin cross-bridges to bind to actin. The sarcoplasmic reticulum stores the cytosolic calcium within the muscle fiber (1).

Summary of Events

1. Action potential propagates along the muscle cell membrane and into T-tubules.
2. Ca2+ releases from terminal cisternae. 
3. Ca2+ binding to troponin encounters removal, blocking the action of tropomyosin. 
4. Cross-bridges bind, rotate, and generate force. 
5. Ca2+ is transported back into the sarcoplasmic reticulum. 
6. Ca2+ removal from troponin restores tropomyosin blocking action. 

Mechanism of cytosolic Increase in Ca

The T-tubule is a protein modified by calcium.

The dihydropyridine (DHP) receptor is a receptor on the L-type Calcium channel linking to cardiac muscle. The receptor acts as a voltage sensor (1).

The ryanodine receptor is a receptor that is connected to the DHP receptor and forms a Ca2+ channel. During an action potential, the DHP receptor will sense the calcium and cause a conformational change. This change allows the junctional foot process to open the ryanodine receptor channel (1).

Ca2+ releases from the sarcoplasmic reticulum into the cytosol and is free to bind to troponin (1).

Once contraction reduces, the calcium is concentrated back into the sarcoplasmic reticulum from the cytosol (1).

The pump allows calcium to bind to Ca2+ ATPases, which pump calcium ions from the cytosol back into SR’s lumen (1).

Sliding-Filament Mechanism

Force generation produces the shortening of a skeletal muscle fiber (1).

Force generation is overlapping thick and thin filaments in each sarcomere (1).

When shortening, myosin cross-bridge is attached to a thin filament actin molecule (1).

The Z lines move toward the center of the sarcomere. This movement allows the shortening of the sarcomere (1).

As long as binding sites on actin remain exposed, the cross-bridge cycle repeats (1).

Thin and thick filaments have cross-bridge cycles where they allow filaments to slide, and the sarcomere shortens. 

Cross-Bridge Cycle

1. The cross-bridge cycle starts with the attachment of the cross-bridge to a thin filament.
2. Then, movement of the cross-bridge, producing tension in the thin filament.
3. Next, there is a detachment of the cross-bridge from the thin filament.
4. Lastly, the detachment produces energy across the cross-bridge to attach to a thin filament again and repeat the cycle.

Step 1: cross-bridge binds to actin

Cross-bridge cycling initiates when calcium in the cytosol increases and exposes the binding sites on actin. The cycle begins with the binding of an energized myosin cross-bridge to a thin filament actin molecule.  This binding produces a power stroke in which Pi and ADP release (1).

Step 2: Cross bridge moves

There are energy stores by cocking the spring and released after binding to actin. The link must break to allow the cross-bridge to be reenergized and repeat the cycle (1).

ATP is the molecule that breaks the link between actin and myosin.

Step 3: ATP binds to myosin 

The dissociation of actin and myosin by ATP and actin as an allosteric modulator weakens myosin’s binding to actin (1).

Step 4:Hydrolysis of ATP energizes the cross-bridge.

ATP binds myosin, and hydrolyzation occurs by myosin-ATPase and allows the energized state (1).

Rigor mortis is a state in which skeletal muscles find themselves stuck in a step. ATP needs to dissociate actin and myosin. After a person dies, there is no dissociation and ATP (1).

As ATP declines, calcium leaks out of the sarcoplasmic reticulum and cannot recycle back into the SR due to the lack of dissociation from actin and myosin (1).

That means actin sites are exposed, and cross-bridges bind and undergo power stroke. Since there is no breakage, the thick and thin filaments remain bound to each other in a rigid condition, and the filaments cannot pull past each other (1).

This stiffness disappears after 48-60 hours after death. 

Mechanics of Single-Fiber Contraction

Tension is the force exerted on an object by a contracting muscle (1).

A load is a force exerted on the muscle by an object.

Isometric is a tension that does not shorten or lengthen.

Contraction is a constant length of a muscle. 

Isotonic contraction is a contraction in which the muscle changes length, and the muscle remains constant (1).

Concentric contraction tension exceeds the load; shortening occurs and allows the shortening to occur when tension exceeds the amount (1).

Eccentric contraction is an unsupported load that is greater than the tension generated by cross-bridges (1).

Events of Action Potentials in Muscle Cells

1. Action potential propagates to motor neuron axon terminals. 
2. Ca2+ enters axon terminals.
3. Ca2+ entry triggers ACh release from axon terminals.
4. ACh diffuses from axon terminals to the motor end plate.
5. ACh binds to nicotinic receptors on the motor end plate, increasing their permeability to Na+ and K+.
6. Na+ moves into the fiber, K+ moves out and forms an EPP.
7. Action potential propagates over the muscle fiber surface and into the fiber along the T-tubules.
8. Action potential propagates in T-tubules and induces DHP receptors that are sensitive to calcium. The ryanodine receptor allows the conformation and calcium release into the sarcoplasmic reticulum. 
9. Ca2+ binds to troponin on the thin filaments, allowing tropomyosin to move away. 
10. Cross bridge initiates on the thick filaments and binds to actin.
11. Cross bridge binding triggers the release of ATP hydrolysis products from myosin.
12. ATP binds tropomyosin, breaks the linkage between actin and myosin, and allows cross bridges to dissociate from actin.
13. ATP bound to myosin is split and energizes the myosin cross-bridge.
14. Cross bridges repeat steps, producing thin filaments past thick filaments. 
15. Cytosolic Ca2+ concentration decreases as CA2+ ATPase transports Ca2+ into the sarcoplasmic reticulum.
16. Removal of calcium from troponin restores blockage of actin and tropomyosin. The cross-bridge cycle ceases, and the muscle fiber relaxes. 

Twitch Contractions

Twitch is an individual muscle fiber response to a single action potential (1).

The latent period follows directly after the action potential and is the period before the muscle fiber tension increases (1).

Contraction time is the time interval from the beginning of tension development and at the end of the latent period (1).

Fast-twitch fibers have contraction times as short as 10 msec (1).

Slow-twitch fibers take 100 msec or longer (1).

Isometric twitch contraction has a shorter latent period due to the exercises that are contracting consistently (1).

Isometric occurs when the muscle’s velocity is zero as the load and fiber reach a stable position (1).

Isotonic twitch has a longer latent period because isotonic exercises involve concentric and eccentric contractions. This contraction could be a bicep curl where an individual extends their arm with the weight and then squeezes those bicep muscles as the arm shortens, using a concentric contraction (1).

Load Velocity Relation

Length-velocity has shortened velocity while maximal extending, where there is no load, and these loads get greater and become a maximal isometric tension. The fiber will lengthen at a velocity that increases with pressure (1).

Increasing load on cross-bridges slows forward movement during the power stroke. This movement will reduce the overall rate of ATP hydrolysis and decrease shortening velocity (1).

Frequency-Tension Relation

The summation is the build-up of action potentials that continue to fire during mechanical activity. These action potentials increase muscle tension and allow the build-up of force for an individual carrying heavier weight (1).
Tetanus is a maintained contraction in response to some stimulation. 

Tetanus is a maintained contraction in response to some type of stimulation. 

Unfused tetanus is the tension oscillating between muscle fibers due to relaxation and tensions. Fused tetanus has no oscillations and produces during higher frequencies (1).

Therefore, as action potentials increase, there is more tension, more summation, and unfused tetanus. When there is enough force, fused tetanus will recruit several different muscle fibers for that contraction (1).

Tetanic tension is more significant than twitch tension because of the summation and timing of calcium availability in the cross-bridge binding (1).

Twitch tension occurs due to the sarcoplasmic reticulum’s calcium release (1).

Titin, the protein in muscle tendons, also delays cross-bridge force transmission to the fiber’s ends (1).

Tetanic tension releases so many action potentials that the SR’s calcium release is enough in the cytosol. Even when the Ca2+ has already pumped, there is still enough Ca2+ in the cytosol for contraction (1).

Length Tension Relation

Titin is attached to the Z line at the end of the thick filament. The protein is responsible for the passive elastic properties of related muscle fibers (1).

As stretch increases, passive tension in fiber increases due to titin filaments’ elongation (1).

A muscle fiber’s dynamic tension during contraction can alter based on chaining the fiber length (1).

Optimal length is when the fiber develops the most significant isometric active tension (1).

As the muscle fiber length increases, isometric tension at each length increases. Further lengthening will decrease tension (1).

When muscle fibers relax, elastic properties keep their length near L0, near the optimal length for force generation (1).

As the fiber shortens back toward L0, more filament overlaps, and the tension developed increases the proportion of cross-bridges in the overlap region (1).

Tension will decline at lengths less than L0. The overlapping sets of thin filaments do not have enough sarcomere cross bridges to exert force, and there are lines coding that prevents internal resistance (1).

Skeletal Muscle Energy 

3 Ways a muscle fiber can form ATP

1. Muscle fiber can form ATP through the phosphorylation of ADP by creatine phosphate. Creatine phosphate is a molecule produced from three amino acids and functions as a phosphate donor.
2. Also, muscle fiber forms ATP through Oxidative phosphorylation of ADP in the mitochondria.
3. Muscle fiber forms the ATP by phosphorylation of ADP by the glycolytic pathway in the cytosol.

Creatine Phosphate

Phosphorylation of ADP by creatine phosphate provides a rapid means of forming ATP by contraction (1).

The creatine and phosphate breaking process causes energy to release when ATP bonds break (1).

The energy with a phosphate group transfers to ADP to form ATP in a reversible reaction catalyzed by enzyme creatine kinase (1).

Contraction involves ATP decreasing and ADP increasing since myosin uses ATP. The energy is rapid. A limited amount of ATP forms from this process if the contraction preserves other ATP forms to continue a contractile activity (1).

Oxidative Phosphorylation

Oxidative phosphorylation is another form of muscular activity that uses ATP. After about 5-10 minutes of exercise, this process breaks down glycogen to glucose for energy (1).

The system uses glucose and fatty acids equally and allows energy to sustain for about another 30 minutes during exercise (1).

Glycolysis

When exercise exceeds a higher intensity, ATP breaks down (1).

The glycolytic pathway uses glucose and fatty acids in the absence of oxygen (1).

This pathway is possible because it obtains glucose from the blood or the glycogen stored within the muscle fibers (1).

Muscle activity will then include creatine phosphate and glycogen concentrations. Extra oxygen is needed; for example, if someone is running, they may run out of glycogen stores (1). 

More oxygen is required to metabolize lactate. 

This reaction produces a deep form of breathing. Breathing allows oxygen to metabolize lactate and react anaerobically (1).

That energy will create an oxygen debt due to the need for even more ATP to utilize and produce energy (1).

Muscle Fatigue 

The decline in muscle tension is known as muscle fatigue. 

This decline will include decreased shortening velocity and a slower rate of relaxation (1).

The onset of fatigue will decrease the intensity and duration of contractile activity and the degree of an individual’s fitness (1).

Fatigue often develops slowly with low intensity and extended duration exercises like cyclin or long-distance running (1).

Short-duration, high-intensity exercises will cause fatigue at a faster period (1).

Muscle fatigue follows various types of muscle cells and contractions (1).

During muscle fatigue, more ADP increases from lactic acid. Oxygen-free radicals increase while there is a decreasing Ca2+ release (1).

This decrease in Ca2+ release means less reuptake by the sarcoplasmic reticulum, causing decreased sensitivity of thin filament proteins to calcium and inhibits myosin cross-bridges binding and power-stroke motion (1).

Prolonged exercise includes leaky calcium channels from the SR. This elevation of cytosolic Ca2+ degrades proteins in the muscle (1).

The result is muscle soreness and weakness until the proteins are replaced (1).

Low blood glucose, dehydration, and decreased muscle glycogen will cause fatigue (1).

Central command fatigue occurs in the brain system, where the cerebral cortex fails to send excitatory signals to motor neurons  (1).

This failure causes a person to stop exercising when the muscles have not reached a fatigue point (1).

Therefore individuals’ athletic performance depends on muscles that withstand fatigue for the most extended period and have the mental ability to initiate central commands to tissues to perform even during distressful sensations (1).

This area of science includes sports psychology. Psychologists help athletes become more aware of their bodies and minds by performing visualization exercises involving athletes performing particular activities during a sporting event. That activity trains the athlete’s mental state to transition to their athletic state when performing (1).

The visualization technique puts the athlete in a “winning” state so that when the time comes to perform, they are intuitively performing to their best capabilities (1).

A simple way to trick the brain into exercising longer involves subjects rinsing their mouths with carbohydrate solutions. The carbohydrates perform a feed-forward mechanism in which the brain believes that energy is on the way, inhibiting fatigue (1).

Types of Skeletal Muscle Fibers

There are three types of skeletal muscle fibers.

1. Slow oxidative fibers are type 1. They combine with low myosin-ATPase activity; these fibers have a high oxidative capacity. This capacity means that these fibers produce a lot of ATP and contain large amounts of myoglobin. This oxygen-binding protein allows the rate of oxygen diffusion to increase rapidly and store oxygen. Ample oxygen storage will lead to red muscle fibers, representing an excellent hemoglobin function (1).

Slow oxidative fibers relate to runners that run long distances. These fibers help them preserve large ATP amounts that they can use for extended periods (1).

1. Fast-oxidative-glycolytic fibers (type 2A) are high myosin-ATPase activity. These fibers have a high oxidative capacity and intermediate glycolytic capacity. Glycolytic fibers have few mitochondria but large glycogen stores. That means that there is limited use of oxygen, but the energy is explosive. Sprinters usually have vast type 2A fibers due to the glycolytic ability and myoglobin function relating to white muscle fibers instead of red muscle fibers like the type 1 fibers. 
2. Last is the fast-glycolytic fibers or type 2x. These fibers also have high myosin-ATPase activity and an even higher glycolytic capacity. That means that energy explosiveness is even more powerful with these fibers, but they will fatigue more quickly than any other fiber (1).

Whole muscle Contraction

Different muscles in the body have unique fibers. 

For example, the back has ample storage of slow-oxidative fibers because these fibers consistently maintain energy. Back muscles are essential for posture and must be able to keep activity for long periods without fatigue. That is why these muscles have ample storage of slow-oxidative fibers (1).

Muscles in the arms have a higher proportion of fast-glycolytic fibers (1).

Control of Muscle Tension

Two ways to control tension are by individual fibers or contraction of fibers at different times. Fiber contraction is dependent on the number of fibers in motor units and the number of motor units available (1).

The eye muscle has one motor neuron that innervates 13 fibers. However, in the legs, there may be 100s of motor units (1).

In terms of tension, slow oxidative fibers tend to initiate first. Fast oxidative glycolytic fibers start next. Lastly, fast glycolytic fibers activate last because they cause the most tension and force (1).

This process is the recruitment of motor units. The higher the number of motor neurons, the greater the muscle tension (1).

Motor neurons also refer to the diameter of the axon. The thicker the diameter, the more a synapse can carry a large motor neuron and depolarize (1).

Small motor neurons innervate slow-oxidative motor units. Meanwhile, large motor neurons innervate fast-oxidative neurons (1).

Endurance exercises that use moderate strength will apply more slow oxidative muscle fibers for recruitment (1).

Control of Shortening Velocity

Velocity is by the load on the fiber, speed of the myosin type, and motor units in the muscle (1).

Two motor units of the same type and fiber type will lift a load more forcibly than apart (1).

Muscle Adaptation to Exercise

Denervation atrophy is when muscle fibers become smaller in diameter, and the contraction force decreases (1).

Disease atrophy is when nerve supply lacks for an extended period (1).

Low-intensity Exercise

Low-intensity exercise is known as aerobic exercise, utilizing type 1 fibers (1).

High-Intensity Exercises

Hypertrophy is a term used for muscle fibers that gradually increase in diameter. These fibers shift fast and use more powerful type 2A fibers. Hypertrophy is not the only way to build muscles; for example, when a person regularly exercises, they increase synchronization in the motor unit recruitment of neurons and enhance fast glycolytic motor neurons (1).

There will be a decrease in fast-glycolytic fibers with endurance training and an increase in fast-oxidative-glycolytic fibers. Strength training will have the opposite (1).

Regulatory Molecules that Mediate Exercise-Induced Changes in Muscle  

These signals that act on muscle changes are just beginning to be understood by scientists (1).

These relate to calcium, action potentials, muscle fibers, and tension  (1).

Anabolic steroids can influence muscle strength and growth in specific ways by targeting specific proteins in the body (1). 

Myostatin is a regulatory protein produced by skeletal muscle cells and binds to receptors on those cells. Myostatin prevents excessive muscle hypertrophy and forms a negative feedback process when lifting weights  (1).

Deficiency in myostatin shows excessive muscle growth. 

Effect of Aging

The force of a muscle decreases by 40% during the ages of 30 and 80. The decrease is due to fiber diameter. Diminished physical activity could also be a cause (1).

Noteworthy is that the same intensity and duration of exercise in an older individual will not have the same changes in a younger person; thus, the ability to adapt to exercise and build muscle, speed, or agility decreases with age  (1).

Exercise-Induced Muscle Soreness

Soreness usually comes from damage to muscle cells due to inflammation. Histamine releases because of the immune system and activates pain neurons in the muscle (1). 

Lengthening of muscle fibers usually causes more significant damage when exercising (1).

A phenomenon explains this very well. When running downstairs, eccentric contractions cause more soreness than running up flights of stairs, which uses shortening contractions (1).

Strength gains come from the eccentric portion of muscle movement.

Lever Action of Muscles and Bones

Tendons enact force on bones. 

Flexion is the bending of a limb at a joint. 

Extensions are the strengthening of a limb.

Antagonist are muscles that oppose the movements of a joint

Biceps and triceps are antagonistic towards each other. Both muscles exert a pulling force in opposite directions (1).

Contraction of some muscles leads to different types of limb movement (1).

Flexing the gastrocnemius in the calf relates to the leg’s flexion at the knee (1).

The contraction of the gastrocnemius muscle will also cause contractions of the quadriceps femoris. That contraction causes extension of the lower leg and becomes an antagonist of the gastrocnemius at the knee joint by preventing the knee joint from bending (1).

This contraction will also cause the foot’s expansion at the ankle joint to stand on tiptoe (1).

The tension of muscles will always be higher than the load it supports. For example, a 10kg weight held by the biceps 35cm away from the elbow will utilize that force shown in this equation 10kgx35cm= 70 kg  (1).

Therefore there is 70kg of force or tension exerted by the muscle. Short slow movements will produce faster changes in the hand (1).

Poliomyelitis is a viral disease that destroys motor neurons and leads to paralysis of skeletal muscle. Ultimately, this leads to respiratory failure and death (1).

Muscle Cramps

Cramping involves action potentials firing at abnormal rates. The cause is uncertain—science data shows an electrolyte imbalance in the extracellular fluid surrounding the muscle and nerve fibers (1).

These imbalances result from dehydration and induce an action potential in motor neurons spontaneously and receptively (1).

Another piece of data shows that chemical imbalances within muscle stimulate sensory receptors in the muscle. The motor neurons are activated by a reflex when the signals reach the spinal cord (1).

That is why stretching shows to affect muscle cramps, releasing the tension, lengthening the muscle, and causing fewer action potentials to fire (1).

Data interestingly shows that chemicals in spicy foods can reduce muscle cramps due to the imbalance of electrolytes given to dehydration (1).

Stimulating receptors in sensory neurons in the mouth, throat, and stomach activates neuronal pathways that reduce alpha motor nouns firing in muscle cramps (1).

Gatorade is another way to restore those imbalances and allow fewer action potions to fire  (1).

Cholesterol-lowering medications cause hormonal imbalances that lead to increased cramps (1).

Hypocalcemia Tetany

Hypocalcemic tetany is involuntary tetanic contractions due to extracellular calcium. Calcium decreases 40% of its average value, causing constant contractions (1).

Ca2+ from the SR will always be a necessity for excitation and contraction (1).

Extracellular calcium is different; these changes exert on the plasma membrane. Therefore, low extracellular calcium, or hypocalcemia, will increase Na+ channels and lead to depolarization. The depolarization leads to the spontaneous firing of action potentials (1).

This change increases muscle contractions, which are similar to muscular cramping (1).

Muscular Dystrophy

Muscular dystrophy is a genetic disease usually by males that lead to progressive degeneration of skeletal and cardiac muscle fibers. This disease weakens muscles and leads to cardiac or respiratory failure (1).

The disease is by a defect of a protein called costamere. 

Costameres are proteins that function for structural and regulatory design. These proteins link Z disks for myofibrils to the sarcolemma and extracellular matrix. When the proteins are damaged, less force produces and causes muscular dystrophy (1).

Duchenne muscular dystrophy is a sex-linked recessive disorder. A dysfunction causes the disease in a gene on the X chromosome—which codes for the protein dystrophin (1).

Dystrophin is a costamere protein, and males with an abnormal X chromosome will usually obtain the disease. 

The protein links filaments in actin and proteins in the sarcolemma (1).

As a person ages, the condition worsens and weakens the muscles. Most individuals will not live beyond 20. 

Myasthenia gravis

Myasthenia gravis is a neuromuscular disorder caused by fatigue and weakness. ACh receptors cause this disease. When ACh travels to the motor plate, there is decreased availability for receptors. Since fewer receptors, less ACh concentrates in the synapse, causing muscle weakness since there aren’t enough receptors to bind (1).

Drugs also prevent specific proteins from breaking down ACh.  

Acetylcholinesterase is essential for breaking down ACh, so when this enzyme decreases, it allows the ACh to remain there longer and bind to a receptor (1).

Drugs like pyridostigmine, an acetylcholinesterase inhibitor, prolong when acetylcholine is available at the synapse (1).

Glucocorticoid is another way to prevent the immune response and allow more receptors to bind (1).

Thymectomy is removing the thymus, reducing antibodies, and can reverse symptoms for 50% of patients.

Plasmapheresis is another treatment that replaces the fraction of plasma that contains the offending antibodies (1).

Some patients can undergo a combination of these treatments,  significantly reducing the mortality rate for myasthenia gravis (1).

Smooth Muscle

Smooth muscles are smaller than skeletal muscle fibers. 

They have a single nucleus and can divide through the life of an individual (1).

They also have thick myosin-containing filaments and thin actin filaments (1).

Caldesmon is a protein that associates with thin filaments and functions in regulating contraction. Tropomyosin on smooth muscle has a different purpose than skeletal muscle (1).

Dense bodies are thin filaments anchored to the plasma membrane when fiber shortens; thus, the plasma membrane with actin branches out (1).

They are not myofibrils, like in skeletal muscles. Smooth muscle contraction becomes possible through a sliding filament mechanism (1).

Myosin in smooth muscle is about 1/3 of striated muscle. 

Smooth muscle generates force over a broad range of muscle lengths (1).

Cross bridge activation

1. Ca2+ binds to calmodulin, which is a protein in smooth muscle. Smooth muscle does not have troponin, and thus tropomyosin is never held back. When Ca2+ binds to calmodulin, this structure relates to troponin.
2. The Ca2+ calmodulin complex binds to another protein, myosin light-chain kinase, and activates that enzyme.
3. Myosin light-chain kinase uses ATP to phosphorylate myosin light chains in the globular head of myosin.
4. Phosphorylation of myosin drives the cross-bridge from the thick filament backbone and allows it to bind to actin.
5. Cross bridges go through repeated cycles as long as myosin light chains get phosphorated  (1).

Smooth muscle does not bring as much velocity or strength in skeletal muscle but does not fatigue after short periods (1).

For a smooth muscle to relax, myosin must dephosphorylate. Dephosphorylated myosin is unable to bind to actin. The dephosphorylation happens due to the enzyme myosin light-chain phosphatase (1).

When the calcium in the cytosol increases, myosin phosphorylation will increase and produce more tension. Vice versa, if the cytosolic calcium decreases, dephosphorylation will increase. The result is relaxation (1).

Latch state is when the smooth muscle has elevated cytosolic calcium and remains elevated, even though ATP hydrolysis declines. This process allows smooth muscle to maintain tension in a rigor state (1).

An example is the body’s gastrointestinal tract, where sphincter muscles maintain the contraction for a prolonged period (1).

Sources of Cytosolic Ca2+

One source of calcium is the SR, and the other is extracellular Ca2+ entering the cell through plasma membrane Ca2+ channels (1).

There are no T-tubules in the plasma membrane. Calcium is not always necessary for contraction; sometimes, second messengers generate in the cytosol and bind to chemical messengers. This reaction triggers calcium release from other sites in the SR (1).

Extracellular Ca2+ has voltage-sensitive Ca2+ channels in the plasma and activates by chemical messengers (1).

The calcium in the extracellular fluid is 10,000 times greater than in the cytosol. Therefore, the opening of channels will cause depolarization (1).

Active transport of Ca2+ back into the SR allows relaxation. 

The rate of removal is much slower than skeletal muscle, however. 

Tension in smooth muscle is graded, varying in the concentration of calcium. 

Smooth muscle tone is a process of utilizing cross-bridge activity in the absence of external stimuli (1).

Membrane Activation

Smooth muscles regulate by neurotransmitters, hormones, electrical activity, apocrine factors, and stretch of muscles. Smooth muscle can excite or inhibit smooth muscle contraction (1).

Smooth muscle calcium concentration increases or decreases by graded depolarizations in the membrane potential (1).

Spontaneous Electrical Activity

There are smooth muscles that generate action potentials spontaneously (1).

A pacemaker potential allows depolarization, such as in the heart spontaneously. 

Slow waves are periodic fluctuations. 

Pacemaker cells are in the stomach and the central nervous system.

Nerve Ends of Hormones

Smooth muscle does not have motor end plate regions. 

Axons of neurons enter the region of smooth muscle cells and divide into different areas known as varicosities (1).

Varicosities are vesicles filled with neurotransmitters that release when an action potential passes by (1).

These varicosities reach out to many cells and activate by sympathetic or parasympathetic neurons (1).

Smooth muscle increases or decreases by neural activity, which is different from skeletal muscles. 

Epinephrine activates a-adrenergic receptors and produces contractions in some areas and relaxation in other regions like the airways by acting on b2-adrenergic receptors (1).

Local Factors

Paracrine signals, related to acidity, oxygen, and carbon dioxide concentration, alter smooth muscle tension (1).

Nitric oxide (NO) is a paracrine component that produces smooth muscle relaxation (1).

Types of Smooth Muscle

Single Unit Smooth Muscle 

1. Single unit muscles have synchronous, electrical, and mechanical gap junctions.
2. Some are pacemaker cells.
3. Nerves, hormones, and local factors have single-unit smooth muscles.
4. A Contractile occurs by stretching the muscle.
5. A single unit’s smooth muscle is in the uterus, intestinal tract, and muscles  (1).

Multiunit Smooth Muscle

1. No or few gap junctions.
2. Cells respond independently.
3. Contact response of muscle depends on the number of cells that activate.  
4. Action potentials do not occur.
5. Hormones increase or decrease contractile activity.
6. Stretching will not induce contraction.
7. Multiunit neurons are typical in the lungs and arteries and hairs in the skin  (1).

Cardiac Muscle

1. Cardiac muscle is striated. 
2. The cardiac muscle has troponin and tropomyosin. 
3. T-tubule connects to the sarcoplasmic reticulum with the storage of calcium. 
4. Cardiac cells are small and have adjacent cells called intercalated discs. There are also gap junctions that help with the transition of neurotransmission  (1).

Excitation Contraction

Depolarizations allow the influx of calcium through individual voltage-gated calcium channels called L-type Ca2+ channels (1).

This reaction triggers the release of even higher amounts of calcium in the sarcoplasmic reticulum (1).

Ryanodine receptors allow the calcium channels to be open, and the voltage change allows the release from the SR (1).

Cross bridge cycling occurs with force generation, similar to skeletal muscle (1). 

There is heavy use of extracellular calcium in the heart; this process is more critical than skeletal muscle (1).

Contraction ends when calcium is restored and pumped back into the SR (1).

A twitch in cardiac muscle exposes 3% of cross-bridge activity (1).

Hormones and neurotransmitters help modulate calcium even more for contractions, especially when exercising (1).

Cardiac muscle cannot occur under tetanic contractions, and the contractions prolong longer due to the calcium current from L-type channels (1).

That way, it prevents multiple cardiac action potentials during the stimulus of a single twitch. This change allows the heart to regulate in an oscillating pump (1).

 Otherwise, too much blood could pump through the heart, preventing relaxation and adequate time for blood filing. The prolonged time allows the heart to fill with blood and allows a noticeable contraction and ejection (1).

Pacemaker potentials in the heart are what initiates potentials in the cardiac cells through gap junctions. These junctions propagate throughout the entire heart (1).

Control of Body Movement

Descending neuron pathways control neurons in the skeletal system via the motor control hierarchy’s local level (1).

The sensorimotor cortex describes different frontal and parietal lobes that control muscle movement (1).

Proprioception has afferent information about the body’s position and spatial awareness (1).

The system allows the body to make real-time adjustments related to muscle movement, like picking up a heavier than an expected package that requires more muscles to maintain the weight (1).

This system also includes reflex circuits and allows the receiving of ongoing movements (1).

Higher centers involve neurons involved in memory, emotions, motivation, and the sensorimotor cortex (1).

The middle level includes subprograms through descending pathways to the local control level. The structures are the sensorimotor cortex, cerebellum, basal nuclei, and brainstem nuclei (1).

The local level includes muscles that carry out programs and subprograms from the middle control levels. The structures include brainstem or spinal cord interneurons, afferent neurons, and motor neurons  (1).

Voluntary and Involuntary Actions

Voluntary movement is conscious awareness of the body and the attention directed towards a particular action. Involuntary is automatic or unconscious reflexes (1).

Local control systems respond to neurons by allowing sensory receptors in muscles, tendons, joints, and skin to move and take in information by enabling higher hierarchy levels to decode that information (1).

Interneurons are 90% of the spinal cord neurons. They are essential for the motor control hierarchy and integrate information towards the central and peripheral receptors (1).

They enable a movement to be turned on or off under a command (1).

Local Afferent Input

Afferent fibers carry information towards the sensory receptors located in the skeletal muscles, tendons, joints, and skin. These receptors are responsible for monitoring the length, tension, and movement of joints (1).

Length-Monitoring Systems

Stretch receptors have what are called afferent nerve fibers wrapped around muscle fibers. These fibers enclose themselves in a capsule that fills with connective tissue (1).

The muscle spindle is the term for the apparatus that involves muscle fibers in a capsule (1).

Intrafusal fibers are modified muscle fibers within the spindles.

Extrafusal fibers form the bulk of the muscle and generate force and movement. 

Nuclear chain fiber responds to muscle stretch; nuclear bag fibers react to the stretch and speed of muscles. These are muscle-spindle stretch receptors (1).

Muscle spindles are parallel to extrafusal fibers. 

Alpha motor neurons are neurons that activate external fibers for force (1).

Alpha gamma coactivation causes the muscle spindles to maintain as the muscle shortens. The tension on the spindles supports the sensitivity of the stretch (1).

Gamma motor neurons are on the ends of intrafusal fibers and activate by smaller diameter neurons (1).

Gamma motor neurons are on the ends of intrafusal fibers and are activated by smaller diameter neurons (1).

The Stretch Reflex

The stretch reflex is when afferent fibers divide into different paths. One path for neurons is excitatory due to a motor neuron’s direct synapse that stretches (1).

The reflex is essential in maintaining balance and posture. 

One example is the knee-jerk reflex. 

An examiner taps a patellar tendon; this tendon connects extensor muscles in the muscle to the lower leg’s tibia. The tendon is pushed in by tapping; the thigh muscle is activated, and stretch receptors activate the muscles (1).

A burst of action potentials allows afferent nerve fibers from the stretch receptors to create excitatory synapses on the motor neurons to control these muscles (1).

As the motor units are isolated, thigh muscles contract and the leg extends (1).

Monosynaptic reflex is a reflex in which the stretched muscle synapses directly on the motor neurons. The synapse to that muscle occurs without any interneurons activated (1).

While one muscle activates another muscle, there is inhibition of the antagonistic muscle. For example, if your quadriceps extend, the hamstrings will also contract to limit the motion range (1).

This homeostasis is known as receptor innervation. The divergence of neuronal pathways initiates both agonist and antagonistic muscles (1).

Polysynaptic neurons are when interneurons come into play between different afferent neurons (1).

 Synergistic muscles assist the current motion, bringing more muscles to allow more force or extension (1).

Tension Monitoring Systems

Golgi tendon organs are encodings of afferent nerve fibers that wrap around collagen bundles in the tendons near the muscle. When a muscle becomes stretched, the tendon exerts tension, and the tension straightens the collagen bundles distort the receptor endings (1).

When a muscle actively contracts, the Golgi tendon initiates and activated by descending action potentials to the central nervous system (1).

The Golgi tendons are a way to control the movement and contraction of the extrafusal muscle fibers (1).

The Withdrawal Reflex

Painful stimulation of the skin activates flexor muscles and inhibits extensor muscles like a foot stepping on a nail (1).

The foot stepping on the nail will flex, and at the same time, extensor muscles on the ipsilateral leg will extend for balance. This response is known as the withdrawal reflex (1).

Crossed extensor reflex is when the same stimulus causes the opposite reaction on the body’s opposite side (1).

The leg extending for balance activates motor neurons for the extension, and flexor muscle motor neurons repress (1).

The primary motor cortex releases descending pathways from the sensorimotor cortex’s motor control on the frontal lobe’s posterior part (1).

These areas include the supplementary motor cortex on the frontal lobe’s surface, the somatosensory cortex, and the parietal lobe association cortex (1).

The neurons in the motor cortex that control muscle groups are a part of the somatotopic map (1). 

The purpose of movement and coordination is why anyone can build coordination over time with consistency by utilizing these neural networks repetitively (1).

Subcortical and Brainstem Nuclei

Basal nuclei are part of the subcortical nuclei and consist of structures in the central nervous system that link to the motor system’s parallel circuits (1).

The thalamus is an area in which this circuit facilitates movement. This region is critical for paralysis or stroke; brain damage causes disease or promotes hyper-contraction in muscles (1).

Parkinson’s Disease

Parkinson’s disease damages the basal nuclei due to inhibitory circuits that cause reduced movement and bradykinesia or muscular rigidity at rest (1).

Substantia nigra, are areas of neurons with dark pigment cells that generally project to basal nuclei and release dopamine but instead degenerate in Parkinson’s disease (1).

MPTP 1-methyl-4-phenyl-1,2,36-tetrahydropyridine is a chemical that associates with destroying the substantia nigra (1).

Drugs to treat Parkinson’s could include agonists for dopamine receptors, inhibitors of the enzymes that deter dopamine in the synapses, or components of dopamine itself (1).

Levodopa L-dopa enters the bloodstream and converts neurons into dopamine (1).

Another treatment form is deep brain stimulation. This technique uses the basal nuclei’s overactive areas to initiate and impact the motor system (1).

Cerebellum

The cerebellum is located dorsally in the brainstem. The cerebellum is also essential for posture and movement by the brainstem nuclei and thalamus (1).

This region is overall the basis for the sensorimotor cortex and descends to the motor neurons: the cerebellum affects eyes, skin, muscles, joints, tendons (1).

The cerebellum also helps in coordination. 

Cerebellar disease is when a person cannot perform a limb or eye movement smoothly. There is a tremor that increases movement near its final destination. People with cerebellar disease cannot combine movements of several joints into coordinated action (1).

Descending Pathway

Corticospinal pathways are in the cerebral cortex, and brainstem pathways are in the brainstem (1).

These pathways end at alpha and gamma neurons on descending pathways (1).

The descending fibers affect presynaptic synapses in the central nervous system (1).

 The fibers also synapse on interneurons in the ascending pathways (1).

An example of descending inputs is a doctor performing surgery (1).

Descending inputs will occur in afferent pathways and carry proprioceptive inputs that monitor hand and fiber movements while performing intricate surgery (1).

Corticospinal pathway

Cell bodies of the corticospinal pathway start in the sensorimotor cortex and end in the spinal cord. These pathways are called pyramidal systems due to the triangular shape passing along the medulla oblongata’s surface (1).

In this system, the brain’s right half controls skeletal muscle fibers on the body’s left side (1).

There are more convergent neurons in the sensorimotor cortex; thus, more neurons in the motor system activate motor behavior (1).

Corticobulbar pathways control voluntary movement for distal extremities farther away from the head and neck (1).

Brainstem Pathways

There are axons from neurons in the brainstem that descend into the spinal cord and activate more neurons. These are called the extrapyramidal system (1).

Brainstem descending pathways involve coordinating large muscle groups, including proximal portions of the limb, upright posture, locomotion, and head and body (1).

Muscle tone

There is always slight resistance, even when a skeletal muscle is relaxed (1).

This resistance signifies muscle tone. 

Muscle tone is due to the calcium in the cytosol at the low-level activity for cross bridging. When a person becomes more alert, there is more activation of alpha motor neurons, increasing muscle tone (1).

Hypertonia is an abnormally high muscle tone due to joint movement at high speeds (1).

Upper motor neuron disorders are dysfunctional abnormalities of descending pathways and neurons to the motor cortex (1).

Plasticity is a form of hypertonia. 

The muscle will not increase tone until more stretch is applied (1).

Rigidity is a form of hypertonia where increased muscle contraction is continual, and they are resistant to passive stretch (1).

Muscle spasms are brief involuntary contractions. 

Muscle cramps are prolonged involuntary and painful contractions (1).

Hypotonia is low muscle tone, with weakness and absent reflex response (1).

Flaccid relates with soft muscles related to hypotonic muscles (1).

ALS Amyotrophic Lateral sclerosis

ALS is a disease in which alpha motor neurons degenerate due to atrophy or hypotonia.

There is muscle weakness, and it relates to Lou Gehrig’s disease (1).

The disease is more common in men and results from free radicals that increase during oxidative stress. 

Medications can help with respiratory and physical deficiencies (1).

Maintenance of Upright Posture and Balance

Postural reflex helps to maintain balance by applying afferent pathways of the postural reflex (1).

Afferent pathways come from the eyes, vestibular apparatus, and proprioception (1).

 Efferent pathways are alpha motor neurons of skeletal muscles, and the integration centers are the brainstem and spinal cord (1).

These reflexes help to maintain posture and relate to the crossed-extensor reflex (1).

Interestingly enough, when one sense is lost, another sense can increase. Blind people, even though blind, have a good gauge of balance (1).

A process of losing afferent nerve endings can delay pain signals. Losing interneurons nerve signals can cause paralysis (1).

Large fiber neuropathy is the debilitation of afferent proprioceptive inputs. This debilitation can detriment posture and balance (1).

Walking

Walking uses many muscles. Extensor muscles in the legs are activated while the other leg flexes. The leg that is extending will have contralateral extensions that inhibit flexion. Vice versa, the leg that is flexing will have contralateral flexors that inhibit extension (1).

Network neurons are spontaneous pacemaker properties initiating rhythm (1).

The network produces rhythmic movement of limbs without command inputs from descending pathways or sensory feedback (1).

Walking includes very little brain activity due to the spinal cord’s reflex, generating its circuit system (1).

Afferent inputs and local spinal cord neural networks contact primarily through locomotion (1).

Fine-tuning and neuronal activation occur in the cerebral cortex, cerebellum, brainstem, and spinal cord during locomotion. This tuning includes proprioceptive use to modulate walking forms, such as balance and coordination (1).

There will also be middle and higher-level support for posture that can override commands like running faster, jumping over a puddle, or balancing while walking and running over uneven steps (1).

When there is damage to the sensorimotor cortex, this will disturb the gait and disrupts locomotor control (1).

Overall, the muscular system is terrific in itself. It allows us to move confidently by utilizing our mind and body using a vast and diverse array of neural circuitry (1).

Sources

Hill, Richard W., et al. Animal Physiology. Oxford University Press, 2018.

Vander, Arthur J., et al. Vander’s Human Physiology: The Mechanisms of Body Function. McGraw-Hill Education, 2019.