SKELETAL MUSCLE POWERPOINT
Introduction to muscle types:
Focus on skeletal muscle for now, although smooth muscle will be covered later in the chapter.
Cardiac muscle will be discussed later when covering the cardiovascular system.
All three muscle types (skeletal, smooth, and cardiac) are unique and have specific roles.
Skeletal Muscle:
Skeletal muscle fibers (cells) are used for moving bones via levers and are attached to bones through tendons (dense, regular connective tissue).
Skeletal muscle is voluntary, meaning you have conscious control over it. It is innervated by somatic motor neurons to facilitate movement.
Smooth Muscle:
Involuntary, you do not control its movements.
Found in visceral organs (e.g., digestive tract, urinary system, reproductive system) and vasculature (e.g., arteries, veins).
Smooth muscle does not have a striated (striped) appearance because the arrangement of actin and myosin is less organized.
Cells are fusiform (long and tapered).
Smooth muscle contractions are driven by different innervation mechanisms compared to skeletal muscle.
Cardiac Muscle:
Found only in the heart.
Shares striated appearance with skeletal muscle, but it is involuntary.
Cardiac muscle fibers may have 1 to 3 nuclei and are typically shorter, branched.
They are rich in glycogen to provide energy for prolonged activity.
The activity of cardiac muscle can be influenced by the sympathetic and parasympathetic nervous systems, regulating heart rate and contraction strength.
Cardiac muscle cells have automaticity, meaning they can initiate their own contractions.
Skeletal Muscle Fiber Characteristics:
Skeletal muscle fibers are long (average of 3 cm in length, can be up to 30 cm) and can have a diameter of 100 to 500 micrometers.
Multinucleated, as they result from the fusion of multiple myoblasts.
Striated appearance due to the arrangement of actin and myosin contractile proteins.
Cellular Organization in Skeletal Muscle:
Muscle fibers (cells) are surrounded by a plasma membrane called the sarcolemma.
Satellite cells, which are stem cells, are located between the sarcolemma and the endomysium (connective tissue wrapping around individual muscle fibers).
When muscles are damaged or during growth, satellite cells differentiate into myoblasts, which then fuse to form new muscle fibers or repair existing fibers.
Muscle Group Structure:
Skeletal muscle fibers are grouped into fascicles, which are surrounded by a layer of connective tissue called perimysium.
The entire muscle is surrounded by a connective tissue layer called the epimysium, which also merges with the tendon that connects muscle to bone.
Tendons are made of type I collagen fibers and anchor the muscle to the bone, forming a continuum of connective tissue (from the muscle fibers through connective tissues to the bone).
Dystrophin and Muscle Contraction:
The dystrophin protein links contractile proteins inside the muscle cell to the plasma membrane (sarcolemma).
This linkage allows the contraction force generated within the muscle fiber to be transmitted through the connective tissues (endomysium, perimysium, epimysium) to the tendon and bone.
Muscle Fiber Components:
Sarcoplasm is the cytoplasm of the muscle fiber.
Myofibrils are bundles of long protein filaments (actin and myosin) that fill the muscle fiber. These filaments are responsible for muscle contraction.
Myofilaments are the individual molecules within the myofibrils that interact during contraction.
Glycogen is stored within muscle fibers as an energy source.
Myoglobin binds oxygen and provides it for cellular respiration in the muscle fibers (similar to how hemoglobin works in red blood cells).
Mitochondria in Skeletal Muscle:
Mitochondria are abundant in skeletal muscle fibers because they generate ATP, which is required for muscle contraction.
Mitochondria play a critical role in aerobic respiration, converting glucose into ATP through glycolysis, pyruvate dehydrogenase, and the electron transport chain.
Molecular Level of Muscle Contraction:
Skeletal muscle contraction involves the cross-bridge mechanism between actin and myosin.
The force generated by contraction within the muscle cell must be transmitted to extracellular components, such as connective tissues (endomysium, perimysium, epimysium), to result in movement.
Growth and Repair of Skeletal Muscle:
Satellite cells can proliferate and differentiate into myoblasts during muscle growth or repair.
In adults, satellite cells primarily contribute to muscle repair and regeneration by fusing with existing muscle fibers to aid in their growth and recovery.
Presence of Myoglobin in Skeletal Muscle
Myoglobin is a pigment located deep within the skeletal muscle.
Skeletal muscle fibers are packed with myofibrils and have limited cytosolic fluid, relying on diffusion to deliver oxygen to the mitochondria.
Myoglobin binds oxygen, acting as a local oxygen reserve inside the muscle fibers.
Its function is to supply oxygen to the mitochondria within skeletal muscle fibers, which is crucial for energy production.
Sarcoplasmic Reticulum (SR)
The SR is a smooth, web-like structure that surrounds myofibrils within skeletal muscle fibers.
The SR is equivalent to smooth endoplasmic reticulum (ER) in other cells.
Functions of SR:
Sequesters calcium ions, which are essential for muscle contraction.
The SR is involved in cholesterol and phospholipid biosynthesis.
Terminal Cisterns
Terminal cisterns are enlarged sections of the sarcoplasmic reticulum (SR).
These dilated sacs are on either side of the transverse tubules (T-tubules).
The SR forms these terminal cisterns to store calcium, crucial for muscle contraction.
Transverse Tubules (T-Tubules)
T-tubules are openings in the plasma membrane (sarcolemma) of skeletal muscle fibers.
They are described as "manholes" that go through the plasma membrane, extending into the muscle fiber.
T-tubules increase the surface area of the muscle fiber.
T-tubules allow action potentials to travel deep into the muscle fiber, reaching all parts of the fiber.
Action Potential and Muscle Contraction
Action potentials travel along the sarcolemma (plasma membrane) and down T-tubules.
As action potentials travel, they stimulate terminal cisterns in the SR, causing calcium channels to open.
Calcium floods the interior of the muscle fiber, which triggers muscle contraction.
The interaction of myofilaments in the muscle fiber leads to contraction when calcium is present.
Calcium Regulation in Muscle Contraction
Increased calcium concentration inside the muscle fiber results in contraction.
After contraction, calcium is pumped back into the SR (resequestered) by calcium ATPase pumps for relaxation.
The cycling of calcium release and resequestration regulates muscle contraction and relaxation.
Triad Structure
The triad consists of a T-tubule and the terminal cisterns on either side of it within the muscle fiber.
This structure is crucial for muscle contraction, as it ensures calcium is released rapidly when needed.
Calcium Storage in the Sarcoplasmic Reticulum
Calcium in the SR is bound to a protein called calquestrin to prevent precipitation due to high concentrations.
This binding ensures calcium remains in solution within the SR and can be released when necessary.
Muscle Repair: Myoblasts and Satellite Cells
Satellite cells are muscle stem cells that differentiate into myoblasts for muscle repair.
Myoblasts are the precursor cells that form new muscle tissue.
Differentiation of satellite cells can be identified by specific protein markers such as MyoD.
Trauma and Muscle Damage
In severe muscle damage (e.g., trauma), satellite cells differentiate to repair the muscle.
If there is significant muscle damage, muscle tissue may become necrotic (dead tissue) and may need to be removed.
Compartment Syndrome
Caused by excessive inflammation and bleeding within the muscle group, which is trapped by the connective tissue sheath.
The buildup of pressure in the confined space compresses blood vessels and nerves, impairing muscle function.
Compartment syndrome requires a fasciotomy, where the fascia (connective tissue layer) is cut open to relieve pressure and restore blood flow and nerve function.
Skeletal Muscle Regeneration After Injury:
After a surgery or muscle injury, satellite cells are often thought to repair muscle, but regeneration is limited.
Example: Alex Smith's leg injury – infection led to removal of skeletal muscle, and the muscle does not fully regenerate.
Textbooks often oversimplify the regenerative abilities of skeletal muscle, suggesting extensive regeneration, but it is actually quite limited.
Hypertrophy of Skeletal Muscle:
Hypertrophy (muscle growth) typically occurs by increasing the size of existing muscle fibers rather than generating new fibers.
This growth is achieved by biosynthesizing more contractile proteins, not by generating new fibers.
Myofilaments:
Myofilaments are proteins that make up the muscle fibers.
Thick Filaments: Comprised of myosin, which is a motor protein, capable of hydrolyzing ATP (ATPase activity).
Thin Filaments: Comprised of actin.
Myosin Structure:
Myosin is composed of two heavy chains and four light chains.
The heavy chains form the tail, and the globular head groups have binding sites for actin and ATP.
Myosin’s ATPase activity helps break down ATP into ADP and inorganic phosphate.
The neck region (or linker) plays a role in smooth muscle contraction.
Filamentous Actin (F-Actin):
Actin is a contractile protein that exists as G-actin (globular actin) when monomeric.
G-actin polymerizes to form filamentous actin (F-actin).
F-actin is often described as a "string of pearls" and is twisted into a filament structure.
Regulatory Proteins in Muscle Contraction:
Tropomyosin: A long, hot-dog-shaped molecule that extends over 7 G-actin monomers. It covers the binding sites on actin, preventing myosin from binding to actin.
Troponin: A complex of three subunits (Troponin C, Troponin I, and Troponin T):
Troponin C binds calcium, which triggers muscle contraction.
Troponin I is the inhibitory subunit, preventing tropomyosin from moving until calcium binds to Troponin C.
Troponin T binds to tropomyosin, anchoring the complex.
Muscle Contraction Mechanism:
Calcium release from the sarcoplasmic reticulum binds to Troponin C, causing a conformational change.
This change moves tropomyosin off the actin binding sites, allowing myosin head groups to bind to actin and form cross-bridge attachments.
The myosin head then hydrolyzes ATP, moving actin filaments toward the center of the sarcomere, leading to muscle contraction.
Sarcomere and Muscle Contraction:
Sarcomere: The functional unit of muscle contraction, defined from Z disc to Z disc.
During contraction, the Z discs move closer together, but the thick and thin filaments themselves do not shorten.
Muscle contraction occurs as myosin heads pull actin filaments toward the M line of the sarcomere, increasing the overlap between actin and myosin.
Titan Protein:
Titan is the largest protein in the human body and runs through the center of the thick filament.
It is a stringy, coiled protein that connects to the Z disc and the M line, securing and positioning thick filaments during contraction.
Z Disc and M Line:
The Z disc and M line are protein complexes that help organize and position thick and thin filaments within the sarcomere.
During contraction, the Z discs move closer, allowing more overlap between actin and myosin, but the filaments themselves do not shorten.
Introduction and Terms:
Myofilaments are bundles of protein chords making up the Myofibrils in skeletal muscle fibers.
Myofilaments can be broken down into their molecular components.
The sliding filament theory explains the contractile mechanisms during muscle contraction.
Regulatory proteins Tropomyosin and Troponin are associated with thin filaments.
Myofilament Structure:
Myofilaments are anchored to Z discs (Z lines), which define the borders of a sarcomere.
Titan (the largest protein in the human body) runs through the core of the filaments and is anchored in the M line, a protein complex that acts as a scaffolding for thick filaments.
Z discs are essential in defining the borders of the sarcomere, the functional unit of contractility in skeletal muscle.
During muscle contraction, the Z discs move closer to one another.
Z Discs and Complex Protein Structure:
The Z discs are composed of hundreds or thousands of proteins, making them one of the most complex multi-protein scaffolding units in the body.
Costamere is a protein complex that connects contractile proteins within the sarcoplasm to the transmembrane protein complexes.
Dystrophin is part of the costamere, linking intracellular proteins to the cell membrane and extracellular matrix.
Dystrophin and Function:
Dystrophin links the contractile proteins to the sarcolemma and the connective tissues surrounding the muscle fiber (endomycium, perimysium, epimysium, tendon, and bone).
Without this linkage, muscle contraction would not result in movement of bones or body parts, as the force would not be transmitted outside the muscle cell.
Muscular Dystrophy:
Mutations in dystrophin cause muscular dystrophy, particularly Duchenne's muscular dystrophy, which is the most common form.
Duchenne's involves the deletion of multiple exons in the dystrophin gene.
Duchenne's muscular dystrophy leads to loss of force transmission from actin filaments to the plasma membrane, causing muscle breakdown.
The disease primarily affects males due to its X-linked inheritance pattern, and symptoms often include profound weakness starting in the hips and thighs.
By age 12, boys with Duchenne's are typically wheelchair-bound due to weakness in the lower body muscles.
Some affected individuals may require ventilation due to respiratory muscle weakness.
Muscle tissue may appear enlarged due to replacement by adipose tissue, but it is not functional.
There is no cure for muscular dystrophy, though treatments exist to manage symptoms.
Sarcomere and Banding Patterns:
The sarcomere is the functional unit of skeletal muscle and extends from one Z disc to another.
A bands (dark bands) represent the entire length of thick myosin filaments, while I bands (light bands) represent areas where only thin actin filaments are present.
The alternating pattern of A bands and I bands gives skeletal muscle its striated appearance.
The A band encompasses thick myosin filaments, and the I band contains thin actin filaments.
Sarcomeres shorten during muscle contraction as the Z discs move closer together, but the length of the A bands and I bands does not change.
Sliding Filament Theory:
In muscle contraction, the actin (thin) filaments slide over the myosin (thick) filaments, causing them to overlap more without changing their length.
This overlap is the primary mechanism of muscle shortening, not the shortening of the individual filaments.
The globular heads of myosin attach to actin and perform a power stroke, moving the thin filaments closer to the M line.
Sarcomere Structure and the M Line:
M line: A protein complex in the center of the sarcomere, serving as a scaffolding structure for thick filaments.
H band: The lighter region in the middle of the A band, containing only thick filaments.
The Z disc bisects the I band, and the M line bisects the H band.
Titan proteins run through the center of the thick myosin filaments, helping anchor them to the M line.
Overview of Skeletal Muscle Organization:
Muscle group: The organ composed of skeletal muscle tissue, which attaches to bone via tendon.
Fascicles: Bundles of muscle fibers, each covered by the perimysium.
Skeletal muscle fiber: A muscle cell covered by the endomysium.
Myofibrils: Protein cords within the muscle fiber, made up of thick (myosin) and thin (actin) filaments.
The sarcomere is the basic unit of muscle contraction, made up of myofilaments (myosin and actin) organized within the myofibrils.
The hexameric arrangement of thin actin filaments surrounds the thick myosin filaments.
Transverse Cuts of Myofibrils:
A transverse cut through a Z disc shows thin actin filaments and Titan proteins.
A transverse cut through the I band shows the arrangement of thin filaments and Titan.
A transverse cut through the M line and H zone shows only thick myosin filaments, with Titan running through their center.
Contraction and Sliding Filament Mechanism:
During muscle contraction, the thin actin filaments are pulled closer to the M line, creating more overlap with the thick myosin filaments.
The thick myosin filaments remain stationary, and the thin actin filaments move toward the center of the sarcomere, causing the Z discs to move closer together.
This results in the sarcomere shortening and muscle contraction, but the length of the individual filaments remains the same.
Overview of skeletal muscle fibers:
Discusses the structure of a single skeletal muscle fiber (cell).
Protein cords within the muscle fiber.
Transverse Tubules (T-tubules):
The plasma membrane invaginates to form the transverse tubules.
Transverse tubules allow the action potential to propagate across the skeletal muscle fiber.
T-tubules connect the outside of the cell to its interior.
Sarcoplasmic Reticulum (SR):
The SR has swollen areas called terminal cisterns on either side of the transverse tubules.
The structure formed by the transverse tubules and the terminal cisterns is known as a triad.
The SR stores calcium ions, which are essential for muscle contraction.
Connections between T-tubules and Sarcoplasmic Reticulum:
The transverse tubules are functionally connected to the sarcoplasmic reticulum.
Importance of these connections in action potential transmission.
Role of Somatic Motor Neurons:
Action potentials are triggered in the sarcolemma (muscle plasma membrane) by somatic motor neurons.
Action potentials spread across the surface of the skeletal muscle fiber.
Bidirectional Action Potentials:
Action potentials propagate in all directions across the sarcolemma when triggered by somatic motor neurons.
These action potentials travel down the transverse tubules.
Voltage Sensors and Receptors:
Dihydropyridine (DHP) receptors are voltage sensors that detect the action potential.
DHP receptors are transmembrane proteins that pick up voltage changes during the action potential.
DHP receptors are connected to ryanodine receptors, which are calcium channels on the sarcoplasmic reticulum.
The interaction between DHP receptors and ryanodine receptors is crucial for calcium release.
Calcium Release Mechanism:
The ryanodine receptor releases calcium from the SR into the sarcoplasm when triggered.
The release of calcium from the SR leads to muscle contraction.
Troponin and Calcium Interaction:
Calcium binds to troponin C, which is a subunit of the troponin complex.
When calcium binds to troponin C, it causes a conformational change that moves the inhibitory subunits away.
This allows tropomyosin to move, exposing binding sites on actin for cross-bridge formation.
Cross-Bridge Formation:
The globular heads of myosin bind to exposed sites on F-actin (filamentous actin).
This forms a cross-bridge, essential for the sliding filament mechanism.
The sliding filament theory explains how the Z-discs move closer together, causing muscle contraction.
Summary of Calcium's Role:
The release of calcium from the SR initiates contraction by binding to troponin C and allowing cross-bridge formation.
Neuromuscular Junction:
The neuromuscular junction is where the somatic motor neuron meets the skeletal muscle fiber.
The somatic motor neuron releases acetylcholine (ACh) to stimulate the muscle fiber.
ACh binds to receptors on the muscle's sarcolemma, initiating action potentials.
Structure of the Neuromuscular Junction:
The axon terminal of the motor neuron branches and has terminal boutons.
One motor neuron can branch and innervate multiple skeletal muscle fibers, forming a motor unit.
In large muscles (like the quadriceps), one motor neuron can innervate thousands of muscle fibers.
Motor Unit and Contraction:
The motor unit refers to the single motor neuron and the muscle fibers it innervates.
All the fibers in a motor unit contract simultaneously when the motor neuron is stimulated.
Motor End Plate and Junctional Folds:
The motor end plate is the region of the sarcolemma directly below the motor neuron's axon terminal.
The motor end plate has junctional folds that increase surface area for acetylcholine receptors.
The folds enhance the efficiency of acetylcholine binding and the subsequent initiation of action potentials.
Importance of Junctional Folds:
The junctional folds help accommodate more acetylcholine receptors, ensuring effective stimulation of the muscle fiber.
Motor End Plate and Junctional Folds
The motor end plate has junctional folds to increase surface area.
This increase in surface area allows for 50 million acetylcholine receptors to be present.
Synaptic Vesicles and Acetylcholine Release
Synaptic vesicles contain acetylcholine.
Action potential travels down the motor neuron to the terminal bouton.
Calcium influx triggers the fusion of neurotransmitter vesicles with the presynaptic membrane.
Approximately 60 vesicles fuse per action potential.
Each vesicle contains 10,000 molecules of acetylcholine.
Excitation Mechanism
The action potential in the somatic motor neuron causes acetylcholine release at the neuromuscular junction.
Excitation involves the transmission of the action potential from the motor neuron to the sarcolemma of the skeletal muscle fiber.
Excitation-contraction coupling includes the release of acetylcholine, leading to an influx of calcium.
Acetylcholine Receptors and Local Potentials
Acetylcholine receptors on the motor end plate are ligand-gated ion channels.
These receptors are permeable to sodium and potassium.
The net effect of acetylcholine binding to the receptors is depolarization due to sodium influx, generating a local potential (called end plate potentials).
End plate potentials are graded potentials, not action potentials.
End plate potentials generate EPSPs (excitatory postsynaptic potentials), causing small depolarizations.
Resting Membrane Potential and Graded Potentials
The resting membrane potential of a skeletal muscle fiber is about -90 mV (more negative than neurons).
The end plate potential (EPSP) shifts the resting membrane potential towards -85 mV or slightly less (slight depolarization).
These EPSPs are graded potentials that sum up across the motor end plate to reach threshold and generate an action potential.
Threshold and Action Potentials
If enough EPSPs accumulate at the motor end plate, they will spread to the adjacent regions of the sarcolemma, reaching voltage-gated sodium channels and voltage-gated potassium channels.
This results in the generation of an action potential across the sarcolemma.
The action potential travels down the sarcolemma and along the transverse tubules.
DHP and Ryanodine Receptors
DHP (Dihydropyridine) receptors on the transverse tubules sense membrane voltage changes (action potential).
Ryanodine receptors are linked to DHP receptors and are responsible for the release of calcium from the sarcoplasmic reticulum into the sarcoplasm.
Calcium Release and Muscle Contraction
The released calcium binds to troponin C on the actin filaments.
This causes a conformational change, moving tropomyosin and exposing the binding sites on actin.
The myosin globular head groups bind to the exposed sites, forming cross-bridges and initiating contraction.
Excitation and Contraction Coupling
Excitation is the process where an action potential in a somatic motor neuron leads to an action potential in the muscle fiber.
Excitation-contraction coupling involves the sequence of events that release calcium, allowing contraction mechanisms to take place.
Voltage-Gated Channels and Action Potential Propagation
Voltage-gated sodium channels open when threshold is reached, leading to depolarization.
Voltage-gated potassium channels open to repolarize the membrane.
These channels contribute to the propagation of the action potential along the sarcolemma.
Motor Unit and Muscle Fiber Innervation
A single somatic motor neuron can branch and innervate multiple skeletal muscle fibers.
A motor unit consists of one motor neuron and all the muscle fibers it innervates.
In large muscles (e.g., quadriceps), a single motor unit can innervate 1000 or more muscle fibers.
Acetylcholine Receptors and Graded Potentials
Nicotinic acetylcholine receptors are always excitatory.
End plate potentials (EPPs) are local potentials generated by acetylcholine binding to its receptors.
These EPPs contribute to generating an action potential when enough depolarization occurs.
Excitation-Contraction Mechanism Summary
Excitation: The action potential travels along the motor neuron, leading to the release of acetylcholine at the neuromuscular junction, which causes depolarization on the muscle's motor end plate.
Contraction: Calcium is released, binds to troponin C, and initiates the sliding filament mechanism.
Excitation-Contraction Coupling: The link between the action potential and the resulting contraction, culminating in muscle shortening.
Lecture Continuation
The next lecture will focus on the sliding filament theory (mechanism of contraction) and relaxation (the turning off of contraction mechanisms).
Power Stroke and ATP Utilization:
Approximately 5 power strokes occur per second.
The stoichiometry of a power stroke is 1:1 with ATP usage (1 ATP per power stroke).
ATP hydrolysis is used to extend the myosin head to the high-energy conformation.
ATP is used during:
Power stroke (myosin pulls actin filament).
Detachment of myosin from actin.
ATP hydrolysis for next cycle.
Electrical Signal and Muscle Contraction:
Electrical signal must occur first before muscle tension can develop.
Action Potential Initiation:
Action potential starts in the somatic motor neuron (neuron that stimulates muscle).
The signal travels across the sarcolemma (muscle cell membrane) and into the transverse tubules (T-tubules).
There is a latent period between the electrical signal and muscle tension.
The latent period is the time between the electrical signal and actual muscle contraction.
Muscle tension can only be generated after the latent period.
Electrical signal occurs first, then muscle contraction begins.
Relaxation Phase:
Cessation of Action Potentials:
Action potentials stop arriving at the somatic motor neuron’s axon terminal.
No more acetylcholine (ACh) is released.
No more electrical signals are sent to the muscle.
Acetylcholine Breakdown:
Without the electrical signal, acetylcholine is not released.
Acetylcholine remaining in the synaptic cleft is broken down by acetylcholinesterase.
Choline is reuptaken and used again.
End Plate Potential:
Without acetylcholine, there is no stimulation of acetylcholine receptors on the motor end plate.
Acetylcholine binds and dissociates continually during each action potential, enabling muscle contraction.
Once action potentials stop, no more acetylcholine is released, and the end plate potential is no longer generated.
No action potentials mean no more calcium release.
Calcium and Muscle Relaxation:
Without continuous action potentials, calcium is no longer released into the sarcoplasm (muscle cell cytoplasm).
Calcium Re-sequestration:
Calcium is pumped back into the sarcoplasmic reticulum by calcium ATPase pumps.
Calcium binds to calquestrin in the sarcoplasmic reticulum.
Decreased calcium levels in the sarcoplasm cause calcium to dissociate from troponin.
When calcium dissociates, the inhibitory subunit of troponin moves back into place.
Tropomyosin covers active sites on actin, preventing myosin from binding.
Myosin heads can no longer interact with actin, leading to muscle relaxation.
Return to Resting Position:
After a muscle contracts, it doesn’t return to its resting length by itself.
Muscles must be brought back to their resting length:
Antagonistic muscle groups (e.g., triceps) contract to extend the muscle.
Gravity also aids in returning the muscle to its resting position.
ATP and Muscle Contraction:
ATP Functions:
Sodium-Potassium ATPase:
Required to maintain ion gradients for action potentials (restoring sodium and potassium gradients).
Calcium ATPase (in the sarcoplasmic reticulum):
Needed for the active transport of calcium back into the sarcoplasmic reticulum after release during muscle contraction.
Cross-Bridge Cycling:
ATP binds to the myosin head, allowing it to detach from actin after a power stroke.
ATP is hydrolyzed to move the myosin head into a high-energy state for the next cycle.
The new ATP allows myosin to detach from actin after the power stroke.
Contraction Does Not Always Mean Shortening:
Contraction refers to the generation of tension, not necessarily shortening.
Tension is generated by the formation of cross bridges.
Example: Holding a dumbbell at a constant position requires muscle contraction to maintain tension, but the muscle doesn't shorten. This is called an isometric contraction (same length).
Types of Contractions:
Isometric Contraction: Muscle generates tension to oppose a load but doesn’t shorten.
Muscle fiber generates tension to overcome the load, which then moves the object.
Muscle Twitch:
The concept of a muscle twitch is introduced.
A myogram is used to illustrate muscle tension over time.
Excitation occurs at the beginning of the twitch when a somatic motor neuron stimulates an action potential in skeletal muscle.
Latent Period:
The latent period is the time between stimulation and muscle contraction.
It involves the steps of excitation (action potential from motor neuron), excitation-contraction coupling (action potentials lead to calcium release and active sites being revealed on actin filaments), and initial tension in contractile proteins (but no outward movement yet).
Excitation-Contraction Coupling:
Excitation leads to an action potential on the sarcolemma (muscle cell membrane).
Excitation-contraction coupling involves the action potential triggering calcium release and revealing active sites on actin for cross-bridge formation.
The muscle contraction starts when calcium binds to troponin C, allowing cross-bridge formation.
Contraction Phase:
Contraction starts when cross-bridge formation occurs, but internal tension develops before physical movement happens.
External tension (movement) occurs after internal tension has been generated.
A myogram illustrates a single muscle fiber twitch, showing contraction and relaxation.
Phases of a Single Muscle Twitch:
Latent Period: Initial delay, includes excitation-contraction coupling and the start of internal tension development.
Contraction Phase: Outward tension generated, resulting in physical movement (cross-bridge cycling).
Relaxation Phase: Calcium is pumped back into the sarcoplasmic reticulum, causing the muscle to relax.
Myogram Insights:
The latent period (time for molecular events to occur) is shown as a delay before the tension builds.
Contraction phase is very fast compared to the relaxation phase, which takes longer due to calcium being pumped back into the sarcoplasmic reticulum.
A muscle twitch duration can range from 7 to 100 ms, influenced by muscle fiber types.
Skeletal Muscle Fiber Types:
Fast Twitch (Glycolytic) Fibers:
Use a fast form of myosin ATPase, enabling quick ATP hydrolysis and short twitch durations.
Slow Twitch (Oxidative) Fibers:
Use a slower form of myosin ATPase, resulting in slower ATP hydrolysis and longer twitch durations.
Intermediate Fibers: A mix of characteristics from both types.
Contraction Strength Factors:
Muscle Starting Length: The initial length of the muscle influences the amount of tension that can be generated (Length-Tension Relationship).
Muscle Fatigue: Repeated use leads to reduced tension generation.
Warm Muscles: Enzymes work more efficiently, improving myosin ATPase activity and overall contraction.
Hydration Level: Dehydration negatively affects cross-bridge formation because thick and thin filaments don't align as well.
Frequency of Stimulation: The rate of stimulation can impact the total tension generated (this will be discussed further).
Motor Unit:
A motor unit consists of one somatic motor neuron and all the muscle fibers it innervates.
When an action potential is fired, all the fibers in the motor unit contract simultaneously as a unit.
In large muscle groups (e.g., quadriceps), many motor units exist. Each motor unit can innervate hundreds to thousands of muscle fibers.
Large motor units (e.g., quadriceps) are used for powerful actions like running and jumping, while smaller motor units are used for more refined movements.
Motor Units and Skeletal Muscle
Multiple motor units contribute to a skeletal muscle group.
Different somatic motor neurons stimulate their respective skeletal muscle fibers.
For powerful actions, more motor units are recruited.
Fine movements (e.g., fingertip movements, facial muscle movements) use motor units with fewer skeletal muscle fibers.
Smaller motor units are recruited for delicate, precise movements.
Muscle Twitch and Strength
Muscle contractions vary in strength depending on the task.
Lifting a light object (e.g., a marker) recruits fewer and smaller motor units.
Lifting heavier objects (e.g., a chair) recruits more motor units with larger fibers.
Muscle contraction strength depends on the number of motor units recruited.
Stimulus and Motor Unit Recruitment
Threshold: Minimum stimulus to trigger an action potential.
Below threshold (stimulus voltages 1 and 2), no action potentials are generated, and no tension is produced.
Threshold stimulus (voltage 3) causes one motor unit to be recruited and results in a small muscle twitch.
As the stimulus voltage increases (voltage 4, 5, and 6), more motor units are recruited to generate more tension.
Maximum recruitment: At stimulus 7, all motor units are recruited, resulting in maximum tension.
At voltages 8 and 9, there is no increase in contraction because all motor units are already recruited.
Multiple Motor Unit Summation: As stimulus voltage increases, more motor units are recruited, which leads to increased contraction. This process is called recruitment or multiple motor unit summation.
Size Principle of Recruitment
Size principle: Smaller, more sensitive motor units are recruited first, followed by larger, more powerful motor units.
Lower voltages recruit smaller motor units for tasks requiring less force.
Higher voltages recruit larger motor units for tasks requiring more force.
Frequency of Action Potentials
Frequency: The speed at which action potentials are fired affects muscle tension.
Single Twitch: A single stimulation results in a complete round of contraction and relaxation.
Temporal Summation: Higher frequency of action potentials results in twitches that overlap, increasing tension.
Incomplete Tetanus: Muscle tension increases because of overlapping twitches.
Complete (Fused) Tetanus: Very high frequency of stimulation results in fused twitches with no relaxation between them.
Physiological Conditions: Fused tetanus does not occur naturally because it would damage muscles. Instead, temporal summation is what happens in normal physiological conditions.
Length-Tension Relationship
There is an optimum sarcomere length (about 2.0 to 2.25 micrometers) for generating the highest muscle tension.
If the sarcomere is too short, the actin filaments overlap excessively with myosin, preventing further contraction.
If the sarcomere is too stretched, there is not enough overlap between actin and myosin filaments to form cross-bridges, resulting in less force.
Optimum resting length is when sarcomeres are at the 2.0 to 2.25 micrometer length.
Physiological Range for Length-Tension
Normally, skeletal muscles are at their optimum resting length due to anatomical structure (e.g., tendon-bone attachments).
Muscles cannot be excessively contracted or stretched without causing damage.
Overly Contracted: If the sarcomere length is less than 60% of the optimum length, it is overly contracted.
Overly Stretched: If the sarcomere length is more than 175% of the optimum length, it is overly stretched.
These extremes are typically observed in laboratory settings (e.g., isolated frog muscle experiments).
Skeletal Muscle in Normal Conditions
Skeletal muscles usually function within the optimum resting length, where they generate maximum tension.
Physiological conditions ensure that the sarcomere length is maintained within this functional range.
Smooth Muscle (Upcoming Topic)
Smooth muscle will be discussed in the next class after the break.
Review of Previous Concepts
Topics discussed earlier in class:
Motor units
Frequency-tension relationship
Length-tension relationship
Moving on to skeletal muscle energy metabolism.
Will also discuss smooth muscle later.
ATP and Skeletal Muscle Contraction
Skeletal muscles require a lot of ATP for contraction.
3 main ways to form ATP in muscle fibers:
Direct phosphorylation by creatine phosphate (first mechanism).
Glycolysis (second mechanism).
Oxidative phosphorylation (third mechanism).
Direct Phosphorylation (First Mechanism)
Creatine phosphate donates a phosphate group to ADP, forming ATP.
Enzyme involved: Creatine kinase.
Another important enzyme: Adenylate kinase (or myokinase).
Glycolysis (Second Mechanism)
Glycolysis occurs in the cytosol and produces ATP through substrate-level phosphorylation.
ATP is generated by transferring a phosphate group from glycolytic intermediates to ADP.
Oxidative Phosphorylation (Third Mechanism)
Occurs in mitochondria and requires oxygen.
Series of steps in the mitochondria:
Pyruvate dehydrogenase complex in the mitochondrial matrix.
TCA cycle (Krebs cycle).
Electron transport chain on the inner mitochondrial membrane.
ATP synthase.
Oxygen is crucial as it acts as the final electron acceptor.
This pathway produces significantly more ATP than glycolysis (30-32 ATP per glucose molecule).
Comparison of ATP Production
Anaerobic fermentation (without oxygen): Produces 2 ATP per glucose molecule.
Aerobic respiration (with oxygen): Produces 30-32 ATP per glucose molecule.
Lactate and Lactic Acid
Lactate is not a toxic byproduct; it is a metabolic fuel.
Lactate can be oxidized by the liver (converted back into pyruvate and used in the TCA cycle).
Lactic acid is not an accurate term; lactate is the correct form.
Continuous Oxygen Supply for Aerobic Respiration
Aerobic respiration requires a continuous supply of oxygen.
Mitochondria are essential for oxidative phosphorylation.
Not all skeletal muscle fibers use mitochondria and oxygen extensively (different fiber types use different ATP production methods).
Types of Skeletal Muscle Fibers
Fast glycolytic fibers:
Rely less on mitochondria.
White in color.
Use anaerobic metabolism for quick bursts of power.
Hybrid fibers: Combination of different metabolic properties.
ATP Sources During Exercise
Start with aerobic respiration (although briefly, usually after more than 40 seconds of exercise).
Progress to phosphagen system (using enzymes like creatine kinase and myokinase).
Shift to anaerobic fermentation (glycolysis and lactate production).
The transition between systems is not abrupt but gradual, forming a spectrum.
Myoglobin and Oxygen Storage in Muscles
Myoglobin in muscle fibers stores oxygen, similar to hemoglobin in red blood cells.
Myoglobin releases oxygen to the muscle cells.
Myoglobin supports the initial seconds of aerobic respiration before full oxygen delivery from the cardiovascular system.
Creatine and ATP Generation
Creatine is synthesized from arginine and glycine in the kidneys.
It forms guanidinoacetate, which is methylated in the liver to form creatine.
Creatine is then transported to skeletal muscles, where it’s phosphorylated to form creatine phosphate.
Creatine kinase catalyzes the phosphorylation of creatine, which can then donate a phosphate to ADP to form ATP.
Role of Creatine and Myokinase
Both creatine kinase and myokinase are involved in generating ATP quickly during intense exercise.
Myokinase catalyzes the transfer of a phosphate from one ADP to another, forming ATP.
Creatine kinase catalyzes the transfer of a phosphate from ATP to creatine, forming creatine phosphate.
Phosphogen System
The phosphogen system is activated for the first 6 seconds of intense exercise.
Enzymes (creatine kinase, myokinase) help quickly generate ATP for short bursts of energy.
Glycogen and Anaerobic Fermentation
As exercise continues, glucose is used to generate ATP via anaerobic fermentation (glycolysis and lactate production).
Glycogen is a storage form of glucose found in muscles and the liver.
Glycogen breaks down to release glucose into the blood and into muscle cells for glycolysis.
Anaerobic Fermentation and ATP Production
Glycolysis occurs in the cytosol and is anaerobic (does not require oxygen).
Glucose is converted to pyruvate, and pyruvate is reduced to lactate.
This pathway generates 2 ATP per glucose molecule, which is much less efficient than oxidative phosphorylation.
Summary of ATP Pathways
Phosphogen system: Uses creatine phosphate for immediate ATP supply.
Glycolysis and anaerobic fermentation: Breakdown of glucose to lactate, producing 2 ATP.
Aerobic respiration: Complete oxidation of glucose to produce 30-32 ATP, requiring oxygen and mitochondria.
Heart and Respiratory System's Role in Oxygen Delivery
The heart's pump ensures blood is pumped to all distal tissues.
Respiratory rate increases to take in more oxygen and deliver it to tissues.
At 40 seconds into activity, the body is able to utilize oxygen and go beyond that mark.
Oxygen Delivery and Mitochondria
Oxygen delivery to tissues is essential for cellular respiration.
Mitochondria are required for cellular respiration (aerobic respiration).
Aerobic Respiration
Aerobic respiration uses oxygen to generate more ATP.
Instead of producing only 2 ATP per glucose molecule, 30 ATP molecules are produced in aerobic conditions.
Fuel Consumption and Glucose vs Fatty Acids
Early on, energy is primarily derived from glucose, either from glycogen or blood glucose.
Anaerobic fermentation requires glucose.
As oxygen consumption ramps up, fatty acids can also be used in aerobic respiration.
Glycogen and Fatty Acids as Energy Sources
For activities like running or exercise lasting about 30 minutes, energy primarily comes from glucose (glycogen breakdown in muscles and liver).
As exercise progresses, the body shifts to using both glucose and fatty acids as fuel.
Higher levels of glucagon stimulate lipolysis, releasing fatty acids for energy.
Aerobic Metabolic Pathways
Metabolic pathways involved in aerobic respiration:
glucose → pyruvate → acetyl-CoA → citric acid cycle → electron transport chain → ATP production.
Oxygen allows pyruvate to enter the mitochondria and undergo complete oxidation, generating up to 30 ATP (depending on the shuttle used).
Oxidative Phosphorylation and Fuel Sources
Oxidative phosphorylation can occur with glucose, fatty acids, and even amino acids (though amino acids are not the preferred fuel for ATP production).
Using proteins as fuel can damage tissues and is not the optimal source of energy.
Lactate and Muscle Fatigue
Lactate is produced during anaerobic glycolysis but does not accumulate in muscle tissue; it is released into the bloodstream and can be used as fuel.
Muscle fatigue involves different mechanisms depending on the type of exercise:
High-intensity exercise (e.g., powerlifting) leads to fatigue through potassium accumulation in transverse tubules, reducing excitability and muscle force production.
Excess ADP and inorganic phosphate slow cross-bridge movements and can inhibit calcium release from the sarcoplasmic reticulum, further reducing muscle contraction force.
Fatigue in Low-Intensity Exercise
In low-intensity exercises (e.g., marathon running), fatigue results from:
Fuel depletion (glycogen stores decline)
Dehydration
Electrolyte loss
Marathon runners consume glucose and electrolyte drinks to maintain energy and fluid balance.
Central fatigue may occur when ammonia levels rise in the blood, impacting the psychological will to continue exercise.
Skeletal Muscle Fiber Types
Fast Twitch vs Slow Twitch Fibers:
The difference between fast and slow twitch muscle fibers lies in the type of myosin heavy chain isoform expressed.
Type 1 (slow oxidative): Exhibits myosin heavy chain 1, slower ATP hydrolysis, and low ATPase activity.
Type 2 (fast twitch): Exhibits myosin heavy chain 2, faster ATP hydrolysis, and higher ATPase activity.
Type 2a (fast oxidative glycolytic): Intermediate fibers with both oxidative and glycolytic capabilities.
Type 2x (fast glycolytic): Fastest ATP hydrolysis, greatest tension generation, and rapid energy use from glycogen (not dependent on mitochondria).
Myosin Heavy Chain Isoforms and ATPase Activity
The rate of ATP hydrolysis and cross-bridge cycling is dependent on the isoform of myosin heavy chain.
Slow oxidative fibers (Type 1) have low ATPase activity, generate less tension, and fatigue slowly.
Fast oxidative glycolytic fibers (Type 2a) and fast glycolytic fibers (Type 2x) generate higher tension and fatigue faster due to higher ATPase activity.
Hybrid Muscle Fibers
Skeletal muscle fibers can be hybrid, expressing combinations of different fiber types.
This can occur during developmental phases, aging, or due to exercise intensity (which can transition muscle fiber types).
Comparison of Muscle Fiber Types
Slow oxidative fibers:
High in mitochondria and capillaries.
Slow to fatigue.
Primarily use oxidative phosphorylation for ATP production.
Fast oxidative glycolytic fibers:
Intermediate in their capabilities.
Rely on both oxidative phosphorylation and glycolysis for ATP production.
Fast glycolytic fibers:
Large diameter.
Rely on glycolysis.
Have a high glycogen content.
Fatigue quickly.
Differences in mitochondria, capillaries, glycogen content, ATPase activity, and fiber diameter define the characteristics of each fiber type.
Concluding Notes on Fiber Types
Type 1 fibers:
Small in diameter with high mitochondria and capillaries.
Type 2 fibers (glycolytic):
Large in diameter with minimal mitochondria.
Rely on glycolysis and fatigue quickly.
Type 2a and 2x fibers:
Fall in between, with 2x being the fastest at ATP hydrolysis and tension generation.
Smooth Muscle Overview:
Involuntary: Smooth muscle operates without conscious control.
Lacks Striations: It is non-striated and has a smooth appearance.
Shape: Smooth muscle fibers are fusiform (spindle-shaped) and taper at both ends.
No Myofibrils: Unlike skeletal muscle, smooth muscle lacks myofibrils (the protein cords seen in skeletal muscle).
No Z Discs: The structural organization of smooth muscle is different from skeletal muscle, so terms like Z discs are not used.
Function and Location of Smooth Muscle:
Visceral Muscle: It’s often referred to as visceral muscle because it lines the walls of hollow organs such as the:
Stomach
Esophagus
Intestines
Urinary bladder
Not an Organ: Smooth muscle does not make up entire organs, but is part of their walls.
Innervation and Control:
Innervation by Autonomic Nervous System (ANS):
Can be innervated or not innervated at all.
If innervated, it’s by the autonomic nervous system, not somatic motor neurons.
Neurotransmitters Involved:
Sympathetic neurons: Release norepinephrine.
Parasympathetic neurons: Release acetylcholine.
The autonomic nervous system modulates contraction, but does not directly control it.
Varicosities and Neurotransmitter Release:
Varicosities: Neurotransmitters are released from swellings along axons called varicosities (small, swelling-like structures along the axon’s length).
Neurotransmitter Vesicles: These swellings store neurotransmitters and release them over a broader area, affecting smooth muscle cells.
Cell Structure and Regeneration:
Single Nucleus: Smooth muscle cells have one nucleus.
Mitosis and Hyperplasia: Smooth muscle cells can undergo mitosis and hyperplasia (growth through cell division), unlike skeletal muscle cells.
Repair: Smooth muscle is easily reparable after damage, e.g., in the stomach or intestines.
Pregnancy Example: The uterus increases in size during pregnancy due to smooth muscle undergoing mitosis and hypertrophy (increase in cell size).
Contraction Characteristics:
Slow Contraction: Smooth muscle contracts much more slowly than skeletal muscle.
Latent Period: The time before peak tension in smooth muscle can be 100 ms (compared to 2 ms in skeletal muscle).
Peak Tension: It takes at least half a second or longer to achieve peak tension.
Relaxation: It takes 1–2 seconds for smooth muscle to relax.
Tetanus Resistance: Smooth muscle can sustain contractions for longer periods without fatiguing.
Size and Length of Smooth Muscle Cells:
Diameter: Smooth muscle cells are 2–10 micrometers wide.
Length: Smooth muscle cells range from 50 to 400 micrometers in length.
Comparison to Skeletal Muscle: Skeletal muscle fibers are larger (10-100 micrometers wide) and much longer (up to 30 cm).
Mechanism of Contraction:
Sliding Filament Mechanism: Like skeletal muscle, smooth muscle contraction occurs via the sliding filament mechanism, but the details are different.
Myosin Light Chain Kinase (MLCK): Smooth muscle uses MLCK to activate myosin cross-bridge formation.
Calcium Binding: Calcium binds to a protein called calmodulin (not troponin) to trigger contraction.
Tropomyosin: Tropomyosin is present in smooth muscle, but it does not play a role in blocking binding sites like it does in skeletal muscle.
Organization of Smooth Muscle:
Dense Bodies: Thin actin filaments in smooth muscle are anchored to dense bodies, which are protein-rich structures found in the cytoplasm and attached to the plasma membrane.
Intermediate Filaments: These help organize the dense bodies and connect them across the muscle cell.
Sarcoplasmic Reticulum (SR): The SR in smooth muscle is sparse compared to skeletal muscle.
Calcium Storage: Calcium is stored in the SR, but smooth muscle also gets calcium from extracellular fluid.
Calcium Entry: Calcium can enter the cell through voltage-gated calcium channels or mechanoreceptors.
Calcium and Contraction Strength:
Graded Contraction: The strength of smooth muscle contraction depends on how much calcium is available in the cell. More calcium leads to a stronger contraction, and less calcium results in a weaker contraction.
No T-tubules: Unlike skeletal muscle, smooth muscle lacks T-tubules, and its architecture is simpler.
Myosin Filaments in Smooth Muscle:
Myosin ATPase Activity: The myosin ATPase activity in smooth muscle is much slower than in skeletal muscle, making cross-bridge cycling slower.
Prolonged Attachment: Myosin heads stay attached to actin filaments for longer periods, contributing to muscle tone (e.g., in blood vessels and digestive organs).
Contraction Shape:
Contraction Appearance: When smooth muscle contracts, the dense bodies pull together, causing the muscle to “pucker” and twist, unlike skeletal muscle which shortens and thickens evenly.
Muscle Tone:
Constant Tone: In smooth muscle, cross-bridges remain attached longer, maintaining a level of muscle tone without fatigue. This helps maintain muscle tension in structures like blood vessels and the digestive tract.
Comparison to Skeletal Muscle:
No Optimal Length-Tension Relationship: Smooth muscle can generate force at various lengths, unlike skeletal muscle, which has an optimal length for contraction.
Cross-Bridge Formation: The lack of regularity in the arrangement of actin and myosin leads to less specific cross-bridge formation compared to skeletal muscle.
Functional Examples:
Location of Smooth Muscle: Found in various parts of the body:
Muscularis mucosa in the digestive tract (e.g., esophagus) helps form folds.
Smooth muscle layers: Inner circular layer and outer longitudinal layer:
Inner Circular Layer: Constricts and narrows the organ, lengthening it.
Outer Longitudinal Layer: Shortens the organ and increases its diameter (dilates).
Peristalsis and Movements
Movements during peristalsis are being discussed.
Peristalsis is a wave-like motion, but the focus seems to be on understanding it in context.
Smooth Muscle Terminology
Muscle fiber vs muscle cell:
"Muscle fiber" is typically used for skeletal muscle because of the length of the cell (e.g., up to 30 cm).
Cardiomyocytes (heart muscle cells) are not referred to as fibers.
Smooth muscle cells are not called fibers because of their appearance and structure.
Two Basic Categories of Smooth Muscle
Smooth muscle is divided into two categories:
Multi-unit smooth muscle
Single-unit smooth muscle (not discussed here but implied as the other category).
Multi-unit Smooth Muscle
Rarity and Location:
Multi-unit smooth muscle is rare and not typically found in organs like the digestive tract or urinary tract.
Location: Found in specific places like large arteries and large airways.
Innervation:
Each individual smooth muscle cell is innervated by one varicosity (a swelling at the end of a nerve).
Varicosity releases neurotransmitters to stimulate a single muscle cell.
The autonomic nervous system controls this.
Sympathetic nervous system releases norepinephrine.
Parasympathetic nervous system releases acetylcholine.
Where Multi-unit Smooth Muscle Occurs
Found in:
Largest arteries (e.g., pulmonary arteries, aorta).
Largest air passages (e.g., primary, secondary, and tertiary bronchi).
Piloerector muscles (muscles that cause hair to stand up, such as when you're cold or scared).
Piloerector muscles:
Smooth muscle at the base of hair follicles contracts, causing hair to stand on end.
Iris of the Eye
Multi-unit smooth muscle is also found in the iris of the eye.
Includes both pupillary constrictor muscles and pupillary dilator muscles (the muscles that control the size of the pupil).
Summary of Multi-unit Smooth Muscle
It is unique in that each smooth muscle cell is individually controlled by a varicosity.
This contrasts with other types of smooth muscle, which may work together as a unit.
Visceral Organs and Single-unit Smooth Muscle
Most organs in the body, especially visceral organs (like the digestive tract, urinary tract, and reproductive tract), are made up of single-unit smooth muscle.
Single-unit smooth muscle is the most common type of smooth muscle in the body.
Multi-unit Smooth Muscle as an Outlier
Multi-unit smooth muscle is rare and does not represent the typical smooth muscle seen in the body.
Single-unit smooth muscle is more common and should be considered the standard when thinking about smooth muscle.
Action Potentials in Multi-unit Smooth Muscle
No action potentials are generated in multi-unit smooth muscle.
Instead of action potentials, neurotransmitters are released onto the muscle, where they bind to cell surface receptors.
The binding of neurotransmitters triggers the release of calcium from intracellular storage.
This is in contrast to what happens in other muscle types where action potentials travel along the cell membrane.
Single-unit Smooth Muscle Structure and Function
Single-unit smooth muscle cells are connected by gap junctions.
This connectivity allows for the synchronized contraction of the entire muscle tissue (the cells contract as a unit).
Multi-unit smooth muscle cells do not have this type of connection and are stimulated individually by neurotransmitters.
Nerve Fiber and Varicosities
In single-unit smooth muscle, nerve fibers (axons) have varicosities (swellings) along their length, which release neurotransmitters onto smooth muscle cells.
A single autonomic nerve fiber can have 2,000 to 20,000 varicosities along its length.
When an action potential travels down the nerve fiber, neurotransmitters are released over a wide area, stimulating multiple smooth muscle cells.
Coordination and Contraction
Because smooth muscle cells are connected by gap junctions, they can contract in unison once stimulated, even when neurotransmitters are released from multiple varicosities.
Arrangement of Smooth Muscle Layers
Visceral smooth muscle typically has two layers:
An inner circular layer.
An outer longitudinal layer.
Some organs have additional layers, such as the stomach (which has three layers) or the urinary bladder (which has multiple layers).
Nerve Terminals and Varicosities
Nerve fibers can branch, and varicosities are present along the branches of the nerve fiber.
The neurotransmitter release from these varicosities covers a larger area of smooth muscle, facilitating coordinated contraction.
Neurotransmitter Release and Smooth Muscle Response
Neurotransmitters are released from synaptic vesicles within the nerve terminal.
The specific response of smooth muscle to neurotransmitters depends on the receptors present on the smooth muscle cells.
Smooth muscle can either be stimulated or inhibited depending on the type of neurotransmitter and the receptors it binds to.
Types of Neurotransmitters and Receptors
Acetylcholine binds to acetylcholine receptors.
Norepinephrine binds to adrenergic receptors:
Beta-2 adrenergic receptors (e.g., in bronchioles) cause relaxation of smooth muscle.
Alpha-1 adrenergic receptors (e.g., in vasculature) cause vasoconstriction (stimulation).
Influence of Other Factors on Smooth Muscle
Smooth muscle can also be influenced by hormones, carbon dioxide, oxygen levels, pH, and temperature.
These factors can stimulate or inhibit smooth muscle contraction.
Complexity of Smooth Muscle Response
Smooth muscle responses can be complex due to the variety of neurotransmitters, receptors, and external factors that influence them.
This complexity means smooth muscle responses are not always straightforward and can vary depending on the specific context (e.g., neurotransmitter type, receptor subtype).
Coldness and Smooth Muscle Contraction
Coldness serves as a stimulus for the contraction of piloerector muscles in the skin, which causes goosebumps.
Stretching and Smooth Muscle Response
Stretching of organs such as the stomach and urinary bladder triggers a contractile response.
These organs do not become flabby when stretched, which indicates the inherent ability of smooth muscle to contract in response to stretch.
Autorhythmicity in Single-unit Smooth Muscle
Some single-unit smooth muscle cells (such as those in the GI tract) exhibit autorhythmicity.
This autorhythmicity involves pacemaker cells that spontaneously depolarize, initiating peristaltic waves (movement in the GI tract).
These cells fire action potentials without external stimulation.
Multiple Stimuli for Smooth Muscle Contraction
Single-unit smooth muscle can be stimulated by various factors:
Hormones
Stretch
Chemicals
Spontaneous electrical activity
Multi-unit smooth muscle does not rely on action potentials for contraction (unlike single-unit muscle).
Calcium’s Role in Smooth Muscle Contraction
The mechanism of contraction and relaxation in smooth muscle primarily involves calcium.
Calcium plays a key role in contraction because smooth muscle has limited sarcoplasmic reticulum (compared to skeletal and cardiac muscle).
There is 10,000 times more calcium in the extracellular fluid than inside the smooth muscle cell.
Calcium is the primary factor involved in smooth muscle contraction, not sodium or potassium ions.
Calcium Channels and Sequestration
Calveoli (small pockets in the plasma membrane) harbor calcium channels to allow calcium entry into the cell.
These areas help sequester calcium for effective use during muscle contraction.
Smooth Muscle Contraction Mechanism
The increase in intracellular calcium is the critical factor for contraction.
Unlike skeletal muscle, smooth muscle does not use troponin. Instead, calcium binds to calmodulin.
Calmodulin has two binding sites for calcium ions, and when calcium binds to it, it undergoes a conformational change.
Calcium-Calmodulin Complex
The calcium-calmodulin complex activates calmodulin kinase (CaM kinase), which then phosphorylates the regulatory light chains of myosin.
This phosphorylation is critical for initiating smooth muscle contraction.
Structure of Myosin in Smooth Muscle
Myosin in smooth muscle consists of two heavy chains and two light chains.
The light chains are of two types: essential light chains and regulatory light chains.
In smooth muscle, regulatory light chains are phosphorylated by calmodulin kinase, leading to the activation of the myosin head, allowing contraction.
Myosin in Smooth Muscle
Myosin in smooth muscle has slow ATPase activity compared to skeletal muscle myosin, which affects the rate of ATP hydrolysis.
The slow ATPase activity of myosin in smooth muscle contributes to its slow contraction cycle.
Contraction Mechanism in Smooth Muscle
After phosphorylation, myosin light chains are activated, allowing the myosin head to move towards thin filaments and bind to them.
This process is similar to the cross-bridge cycling seen in skeletal muscle, involving ATP hydrolysis, power strokes, and contraction.
Myosin Light Chain Phosphatase
Myosin light chain phosphatase dephosphorylates the regulatory light chains, which stops the contraction process.
This enzyme helps turn off smooth muscle contraction by removing the phosphate group from the myosin light chains.
Muscle Tone and Contraction Duration
Smooth muscle can maintain muscle tone, as cross bridges may remain attached even at lower calcium levels, prolonging contraction.
This prolonged attachment can result in continuous muscle tone (e.g., in blood vessels).
Regulation of Contraction and Relaxation
The activity of myosin light chain phosphatase is constitutively active (always present and functional), and its activity can be increased or decreased, but it is often overshadowed by increased calcium levels.
When calcium levels increase, the calcium-calmodulin complex activates myosin light chain kinase, leading to contraction.
If calcium levels drop or are sequestered, the phosphatase can dephosphorylate the regulatory light chains, turning off the contraction.
Sources of Calcium for Smooth Muscle
Calcium for smooth muscle contraction comes from:
Extracellular fluid (calcium entering through calcium channels).
Intracellular stores (calcium released from the sarcoplasmic reticulum).
Summary of Contraction Mechanism
In smooth muscle, the key steps for contraction include:
Calcium binds to calmodulin.
The calcium-calmodulin complex activates myosin light chain kinase.
This kinase phosphorylates the regulatory light chains of myosin.
Phosphorylation of the light chains leads to cross-bridge cycling and muscle contraction.
Relaxation occurs when calcium levels decrease, allowing myosin light chain phosphatase to dephosphorylate the light chains, turning off contraction.