Guyton Module 7

• Around 40% of the body is skeletal muscle, with an additional 10% being smooth and cardiac muscle

Skeletal Muscle Fibers

• Skeletal muscles have numerous fibers, each comprised of smaller subunits
• Each fiber receives innervation from a single nerve ending

Sarcolemma

• The sarcolemma is the membrane that surrounds a skeletal muscle fiber

Myofibrils

• Myofibrils contain actin and myosin filaments
• These filaments are essential for muscle contraction, and they are maintained in arrangement by titin molecules

Filament Types

• Myosin filaments are thick
• Actin filaments are thin

Sarcoplasm

• The intracellular fluid located between myofibrils is the sarcoplasm
• Contains potassium, magnesium, phosphate, protein enzymes, and mitochondria

Sarcoplasmic Reticulum

• The sarcoplasmic reticulum regulates calcium storage, release, and reuptake, controlling muscle contraction

Muscle Bands

• Skeletal and cardiac muscles appear striated due to light and dark bands

I bands

• Light bands contain only actin filaments
• They are called I bands

A bands

• Dark bands contain myosin and overlapping actin filaments
• These are referred to as A bands

Sarcomere

• The sarcomere is the portion of the myofibril located between two successive Z disks

Muscle Contraction

• Muscle contraction happens via a sliding filament mechanism

Key Steps in Muscle Contraction

• An action potential moves along a motor nerve, reaching its endings on muscle fibers
• The nerve then secretes acetylcholine
• Acetylcholine causes cation channels to open, allowing sodium ions to diffuse and leading to depolarization
• The action potential moves along the muscle fiber membrane
• The sarcoplasmic reticulum releases calcium ions
• Calcium ions start forces between actin and myosin filaments and cause them to slide
• Calcium ions are then pumped back into the sarcoplasmic reticulum, stopping contraction

Myosin Molecules

• Have two heavy chains and four light chains
• The heavy chains form a double helix tail, and each chain has a myosin head
• The heads include hinged arms that allow them to extend outward

Actin Filaments

• Actin filaments consist of two helical strands of F-actin molecules
• Tropomyosin molecules wrap around the F-actin helix
• Troponin complexes attach to the tropomyosin

ATP

• ATP is the energy source for contraction
• ATP binds to the myosin head and is cleaved into ADP and phosphate
• The energy released is used for the power stroke

Walk-Along Theory

• Cross-bridges attach to actin filaments, tilt to drag the actin filament, detach, and then reattach to a new active site causing the filaments to slide

Muscle Tension

• The amount of actin and myosin filament overlap determines the tension developed by the contracting muscle

Muscle Work

• Work output during muscle contraction is defined as W = L × D
• W = work output
• L = the load
• D = the distance of movement against the load

Energy Sources

• The three sources of energy for muscle contraction are phosphocreatine, glycolysis, and oxidative metabolism

Contraction Types

• Muscle contraction is isometric when the muscle does not shorten
• It is isotonic when it shortens at a constant tension

Muscle Fibers

• Fast fibers are large, possess an extensive sarcoplasmic reticulum, and rely on glycolytic enzymes
• Slow fibers are smaller, have numerous blood vessels and mitochondria, and contain myoglobin

Motor Unit

• A motor unit consists of a motor neuron and the muscle fibers it innervates

Summation

• Summation raises muscle contraction intensity by increasing the number of motor units contracting (multiple fiber summation) or increasing the frequency of contraction (frequency summation), leading to tetanization

Muscle Fatigue

• Muscle fatigue results from the inability to maintain the required work output, often because of glycogen depletion

Agonist and Antagonist Muscles

• Agonist and antagonist muscles on opposite sides of a joint coordinate body movements

Adaptations

• Muscles adapt through remodeling, including hypertrophy (increase in muscle mass) and atrophy (decrease in muscle mass)

Denervation

• Muscle denervation leads to rapid atrophy

Muscular Dystrophies

• Muscular dystrophies, such as Duchenne muscular dystrophy (DMD), are inherited disorders causing muscle weakness and degeneration

Muscle Fiber Composition

• Each muscle fiber contains hundreds to thousands of myofibrils
• They are composed of actin and myosin

Myosin

• Myosin filaments are thick and dark, comprising the A bands

Actin

• Actin filaments are thin and light, comprising the I bands

Sarcomere Structure

• The sarcomere is the fundamental unit of muscle contraction located between two Z discs

Titin

• Titin connects the Z disc to the myosin at the M line and is springy

Sarcoplasm

• Sarcoplasm is the fluid between the myofibrils
• Contains potassium, magnesium, and phosphate

Sarcoplasmic Reticulum

• The sarcoplasmic reticulum regulates calcium storage, release, and uptake

Myosin Filament Structure

• Myosin filaments consist of a tail, a hinge, and a head
• Myosin molecule tails bundle together to form the body of the myosin
• The arm and head combination is called the cross bridge
• Two hinges exist: one to create the arm and another to attach the head
• Cross bridges extend in all directions around the body

Actin Filament and Contraction Regulation

• Actin is strongly attached to the Z disc
• Tropomyosin wraps around actin, covering active sites until contraction is needed
• Troponin, attached to tropomyosin, has a strong affinity for calcium, initiating contraction
• When the muscle is relaxed, a golf club shaped myosin head is bound by ATP and detached from the thin filament along the actin fiber
• A complex made of tropomyosin, as well as troponin C, component I and troponin T, is in a down position blocking myosin from binding to the active site

Walk Along Theory

• An action potential releases calcium from the sarcoplasmic reticulum
• Calcium causes the myosin heads to attach to active sites on the actin filament
• The cross bridge head tilts, dragging the actin filament along with it
• The head detaches, returns to the extended direction, and attaches to another active site for a new power stroke
• Once the neuromuscular junction has transmitted a signal, calcium concentration in the muscle cell jumps sharply
• The troponin complex has four calcium binding sites, two of which are low affinity sites
• Once these two are filled, the complex undergoes a conformational change which moves it up and away
• This movement allows tropomyosin to relocate, clearing the way for myosin to bind
• Even with the binding site clear, however, myosin will stay in its detached position if it is still bound by ATP, as the ATP has hydrolyzed ATP and inorganic phosphate
• The myosin head rotates back to its cocked position before jumping to an active binding site, forming a cross bridge
• The actual contraction begins when phosphate dissociates from myosin, triggering the power stroke
• The myosin head rotates 45 degrees, pulling the actin along with it
• Once the power stroke is finished, ADP leaves and the cross branch is stuck in the attached and contracted state
• If ADP again binds to the myosin head, then the cycle will start over at the relaxed stage

Energy for Contraction

• Large amounts of ATP are cleaved to form ADP during contraction
• ATP is used to extend the head, and energy is stored for the power stroke
• ATP is needed for the walk along mechanism, pumping calcium into the sarcoplasmic reticulum, and pumping sodium and potassium ions

ATP Formation

• Phosphocreatine: Provides energy for 5-8 seconds
• Glycolysis: Breakdown of glycogen to pyruvic and lactic acid, maintaining contraction for about a minute
• Oxidative Metabolism: Combines oxygen and glycolysis products, providing over 95% of energy used by muscles

Contractions

• Isometric: Same length, muscle does not shorten
• Isotonic: Muscle shortens, tension remains constant

Muscle Fibers

• Muscles contain a mixture of fast and slow fibers

Slow Fibers

• More myoglobin (reddish)
• Higher capillaries
• More mitochondria
• Smaller
• Less strength
• Longer contraction periods

Fast Fibers

• Larger
• Greater strength
• Extensive sarcoplasmic reticulum
• Large amounts of glycolytic enzymes
• Less blood supply
• Fewer mitochondria

Motor Units and Summation

• Each motor neuron innervates multiple muscle fibers, forming a motor unit
• Fine motor control requires more nerve fibers
• Summation is the adding together of individual contractions

Summation

• Increasing the number of motor units contracting simultaneously
• Increasing the frequency of contraction

Size Principle

• Smaller units contract first, then larger units as signal strength increases

Tokenization

• Contractions fuse together at a critical level in appearing smooth and continuous

Muscle Strength and Fatigue

• Maximum strength of contraction is between 3 to 4 kg/cm²
• Staircase effect: Muscle strength increases rapidly after a long rest period
• Muscle tone: Low rate of nerve impulses causing tightness
• Muscle fatigue: Occurs in direct proportion to the depletion of glycogen

Muscle Remodeling

• Hypertrophy results from increased numbers of actin and myosin filaments
• Only a few strong contractions a day are needed for hypertrophy within 6-10 weeks
• New sarcomeres are added when muscles are stretched
• Sarcomeres are removed if a muscle remains shortened for an extended period
• Denervation causes atrophy in just two months
• Renovation can cause return of function, but typically with less capability

Main Themes

• Physiological Anatomy of Skeletal Muscle: Focuses on the structural components of skeletal muscle, from the gross anatomy down to the molecular level
• Mechanism of Muscle Contraction: Describes a step-by-step process of how a muscle fiber contracts, starting with nerve stimulation and ending with the sliding of actin and myosin filaments
• Molecular Basis of Contraction: Explains the roles of key proteins like actin, myosin, troponin, and tropomyosin in the contraction process, including their interactions and energy requirements
• Energetics of Muscle Contraction: Discusses the sources of energy (ATP, phosphocreatine, glycolysis, and oxidative metabolism) that power muscle contraction and the efficiency of this process
• Characteristics of Whole Muscle Contraction: Explores different types of contractions (isometric, isotonic), twitch responses, summation, tetanization, and the factors affecting muscle strength and fatigue
• Remodeling of Muscle: Details how muscles adapt to changing demands through hypertrophy, atrophy, fiber type changes, and adjustments in length
• Muscle Disorders: Touches on conditions like muscular dystrophy, denervation atrophy, and rigor mortis, and the underlying mechanisms

Structure of Skeletal Muscle

• Skeletal muscle comprises approximately 40% of body mass
• Muscles consist of fibers (10-80 micrometers in diameter) made up of myofibrils
• Myofibrils contain interdigitating myosin (thick) and actin (thin) filaments, creating light (I) and dark (A) bands
• Sarcomere: The segment between two Z disks, representing the functional unit of muscle contraction
• Titin molecules maintain the alignment of actin and myosin filaments

Molecular Components and Their Roles

• Myosin: Thick filaments with cross-bridges that interact with actin
• Myosin heads have ATPase activity, which is crucial for energy release during contraction
• Actin: Thin filaments containing active sites for myosin binding
• Tropomyosin: Blocks the active sites on actin in the resting state
• Troponin: Binds calcium ions, triggering a conformational change that moves tropomyosin and exposes the active sites on actin

Sliding Filament Mechanism

• Muscle contraction occurs as actin filaments slide past myosin filaments, shortening the sarcomere
• Cross-bridges on myosin bind to actin, pull the actin filaments, detach, and repeat the cycle ("walk-along" theory)

Excitation-Contraction Coupling

• Action potential travels along the muscle fiber membrane (sarcolemma)
• Depolarization causes the sarcoplasmic reticulum to release calcium ions
• Calcium ions bind to troponin, initiating the contraction process
• Calcium is pumped back into the sarcoplasmic reticulum to allow muscle relaxation

Energy Sources

• ATP provides the immediate energy for muscle contraction
• Phosphocreatine replenishes ATP quickly but is limited
• Glycolysis (anaerobic breakdown of glycogen) provides energy for short-term, intense activity
• Oxidative metabolism (using oxygen to break down carbohydrates, fats, and proteins) provides energy for sustained, long-term activity

Contraction Types

• Isometric: Muscle contracts without shortening (e.g., pushing against an immovable object)
• Isotonic: Muscle shortens while maintaining constant tension (e.g., lifting a weight)

Motor Units

• A motor unit consists of a motor neuron and all the muscle fibers it innervates
• Smaller motor units are recruited first for fine motor control; larger motor units are recruited for more forceful contractions ("size principle")

Summation and Tetanization

• Summation: Increased force of contraction due to multiple stimuli
• Tetanization: Sustained, maximal contraction due to high-frequency stimulation

Muscle Fatigue

• Caused by depletion of glycogen stores and the inability of contractile and metabolic processes to keep up with energy demands

Muscle Remodeling

• Hypertrophy: Increase in muscle mass due to increased size of muscle fibers (increased actin and myosin filaments)
• Atrophy: Decrease in muscle mass due to decreased protein synthesis or increased protein degradation
• Muscle length can be adjusted by adding or removing sarcomeres

Muscle Disorders

• Muscular Dystrophy (e.g., Duchenne): Genetic disorder causing progressive muscle weakness and degeneration due to defects in proteins like dystrophin
• Denervation Atrophy: Muscle atrophy due to loss of nerve supply
• Rigor Mortis: Muscle rigidity after death due to ATP depletion

Neuromuscular Junction

• Large myelinated nerve fibers from the spinal cord's anterior horns stimulate skeletal muscle fibers
• Action potentials travel along these fibers in both directions
• The motor endplate is insulated by Schwann cells
• The space between the nerve terminal and muscle fiber membrane is the synaptic space or cleft
• This area has folds to increase the surface area for synaptic activity

Acetylcholine Synthesis and Release

• ATP is used in the axon terminal to synthesize acetylcholine, which is then stored in synaptic vesicles
• There are roughly 300,000 vesicles in a nerve terminal of a skeletal muscle fiber
• Each vesicle contains about 10,000 acetylcholine molecules
• An action potential typically ruptures about 125 vesicles, releasing over 1.2 million acetylcholine molecules

Acetylcholine Release Mechanism

• When an action potential arrives at the nerve terminal, voltage-gated calcium channels open
• Calcium ions diffuse into the nerve terminal
• Calcium facilitates the binding of acetylcholine vesicles to the neural membrane
• Results in the release of acetylcholine into the synaptic space via exocytosis

Acetylcholine and Ion Channels

• Released acetylcholine stimulates ion channels on the post-synaptic muscle fiber
• Two acetylcholine molecules bind to alpha subunit proteins on the acetylcholine-gated sodium ion channel
• This enables 15,000 to 30,000 sodium ions to pass through in one millisecond The muscle membrane's negative potential (-80 to -90 millivolts) pulls positively charged sodium ions into the muscle fiber

Action Potential and Muscle Contraction

• The influx of sodium ions creates a local positive charge
• Opens neighboring voltage-gated sodium channels and allowing more sodium to flow inward
• Positive charge spreads along the muscle membrane, leading to muscle contraction
• Acetylcholine is rapidly broken down by acetylcholinesterase in the synaptic space, limiting its presence to a few milliseconds
• Acetylcholine binds to connective tissue within the synaptic cleft

Action Effects

• The rapid diffusion of sodium ions causes a change in charge from -80 or -90 millivolts to a positive 50 to 75 millivolts, is called the endplate potential
• An action potential must reach a threshold to cause further action potentials
• Curare poisoning and botulism toxin can weaken the potential which prevents it from reaching the threshold

Drugs and Diseases

• Drugs that mimic acetylcholine can cause localized depolarization and muscle spasms
• Drugs inhibiting acetylcholinesterase lead to acetylcholine accumulation in the neuromuscular junction
• Diseases like Myasthenia Gravis reduce signaling from the nerve fiber or diminish receptors at the post-synaptic junction, impairing ability to initiate a strong action potential
• These conditions can be treated with acetylcholinesterase inhibitors

T Tubules

• Skeletal muscle fibers utilize T tubules to transmit action potentials into the muscle fiber's interior
• These tubules are extensions of the cell membrane and communicate with the exterior of the muscle fiber

Calcium Release and Sarcoplasmic Reticulum

• T tubules are closely associated with the sarcoplasmic reticulum which stores large amounts of calcium ions
• When an action potential occurs in the T tubule calcium ions are released from the sarcoplasmic reticulum
• A voltage change in the T tubule is detected by ryanodine receptor channels in the sarcoplasmic reticulum, opening calcium release channels
• Muscle contraction continues as long as calcium ion concentration remains high

Calcium Pump and Relaxation

• A calcium pump in the sarcoplasmic reticulum walls pumps calcium back into the tubules
• Each action potential stimulation increases calcium concentration significantly, which is then reduced by the calcium pump
• This process, known as the calcium pulse, lasts about 1/20 of a second

Excitation-Contraction Summary

• Action potential travels down the T tubule and stimulates the ryanodine receptor channel, releasing calcium ions from the sarcoplasmic reticulum, leading to muscle contraction
• The calcium pump restores calcium to the sarcoplasmic reticulum

Malignant Hyperthermia

• Mutations in the ryanodine receptor channel can cause malignant hyperthermia, a hypermetabolic crisis triggered by certain anesthetics
• The anesthetics cause unregulated calcium release from the sarcoplasmic reticulum, leading to excessive muscle fiber contraction, heat production, cellular acidosis, energy depletion, and rhabdomyolysis

Neuromuscular Junction

• Skeletal muscle fibers are innervated by myelinated nerve fibers from motoneurons, near the muscle fiber's midpoint
• The nerve fiber branches into terminals that invaginate into the muscle fiber surface, forming the motor end plate
• The invaginated membrane is the synaptic gutter or trough, with a synaptic space (cleft) of 20 to 30 nanometers
• Subneural clefts on the gutter's bottom increase the surface area for synaptic transmitter action

Acetylcholine Release

• When a nerve impulse reaches the neuromuscular junction, about 125 vesicles of acetylcholine are released into the synaptic space
• Calcium ions entering the nerve terminal activate Ca2+-calmodulin–dependent protein kinase, which phosphorylates synapsin proteins
• This frees acetylcholine vesicles to move to the presynaptic neural membrane's active zone
• The vesicles dock, fuse with the neural membrane, and release acetylcholine via exocytosis

Acetylcholine-Gated Channels

• Acetylcholine receptors are located near the mouths of subneural clefts
• Each receptor has two alpha subunit proteins to which acetylcholine molecules attach, causing a conformational change that opens the channel
• These channels positive ions like sodium, potassium, and calcium to move through, repelling negative ions like chloride

End Plate Potential

• The influx of sodium ions through acetylcholine-gated channels creates a local positive potential called the end plate potential
• If potential is strong enough, it opens voltage-gated sodium channels, initiating an action potential
• Acetylcholinesterase in the synaptic space destroys acetylcholine just milliseconds after its release

Safety Factor and Fatigue

• Each nerve impulse causes three times as much end plate potential as stimulus providing a high safety factor
• However, excessive stimulation can deplete acetylcholine vesicles, causing fatigue of the neuromuscular junction

T Tubule System

• Action potentials spread along the muscle fiber membrane and into the T tubules
• T tubules are extensions of the cell membrane that penetrate the muscle fiber and transmit the action potential deep into the muscle fiber to stimulate the sarcoplasmic reticulum

Calcium Release

• The sarcoplasmic reticulum stores calcium ions
• When an action potential reaches the T tubule, it is sensed by dihydropyridine receptors, which trigger the opening of calcium release channels (ryanodine receptor channels) in the sarcoplasmic reticulum
• Calcium ions are released into the sarcoplasm, initiating muscle contraction

Calcium Removal

• A calcium pump (SERCA) in the sarcoplasmic reticulum walls pumps calcium ions back into the tubules
• Calsequestrin, a calcium-binding protein inside the reticulum, can bind up to 40 calcium ions per molecule

Neuromuscular Junction & Transmission

• Anatomy: The neuromuscular junction (NMJ) is where a motor nerve fiber connects with a skeletal muscle fiber
• The nerve fiber branches into terminals that invaginate into the muscle fiber surface, forming the motor end plate
• The invaginated membrane is the synaptic gutter or trough
• The space between the nerve terminal and muscle fiber membrane is the synaptic space (cleft)
• Subneural clefts on the muscle membrane increase surface area

Acetylcholine (ACh) Synthesis and Release

• ACh is synthesized in the nerve terminal cytoplasm, then transported into synaptic vesicles (approx. 300,000 per terminal)
• When a nerve impulse arrives, voltage-gated calcium channels open, causing an influx of Ca2+ ions
• This triggers the fusion of about 125 ACh vesicles with the presynaptic membrane and the release of ACh into the synaptic cleft via exocytosis

ACh Receptors and End Plate Potential

• ACh diffuses across the synaptic cleft and binds to ACh receptors (ligand-gated ion channels) on the muscle fiber membrane, concentrated at the mouths of subneural clefts
• These receptors, composed of five subunit proteins, open a channel allowing Na+, K+, and Ca2+ to pass
• The influx of Na+ causes a localized depolarization called the end plate potential (EPP)

Action Potential Initiation

• If the EPP reaches threshold opens voltage-gated sodium channels initiating an action potential that propagates along the muscle fiber

ACh Degradation

• Acetylcholinesterase (AChE) rapidly hydrolyzes ACh in the synaptic cleft into acetate and choline, terminating the signal
• Choline is reabsorbed into the nerve terminal for ACh resynthesis

Safety Factor and Fatigue

• The NMJ has a high safety factor, meaning the EPP is normally significantly larger than needed to trigger an action potential
• However, sustained high-frequency stimulation can deplete ACh vesicles, leading to neuromuscular junction fatigue

T-Tubules

• Action potentials propagate along the muscle fiber surface and travel into the fiber via transverse tubules (T-tubules), ensuring uniform excitation of the myofibrils

Sarcoplasmic Reticulum (SR)

• The SR is an intracellular network that stores calcium ions
• It consists of terminal cisternae (large chambers abutting the T-tubules) and longitudinal tubules surrounding the myofibrils

Calcium Release

• When an action potential reaches the T-tubules, voltage-sensitive dihydropyridine receptors (DHPRs) on the T-tubule membrane sense the voltage change
• They are mechanically linked to ryanodine receptor channels (calcium release channels) on the SR membrane
• DHPR activation triggers the opening of ryanodine receptors, releasing Ca2+ from the SR into the sarcoplasm (the cytoplasm of muscle cells muscles)

Muscle Contraction

• The increase in sarcoplasmic Ca2+ concentration allows Ca2+ to bind to troponin initiating the cross-bridge cycle and muscle contraction

Calcium Removal

• To terminate contraction, a Ca2+ pump actively transports Ca2+ back into the SR, reducing the sarcoplasmic Ca2+ concentration and allowing the muscle to relax
• Calsequestrin, a calcium-binding protein within the SR, helps store the high concentration of Ca2+ inside the reticulum

Muscle Action Potential

• Resting membrane potential is about -80 to -90 millivolts
• The duration of action potential is 1 to 5 milliseconds in skeletal muscle
• The velocity of conduction is 3 to 5 m/sec

Drugs Affecting Neuromuscular Transmission

• ACh-like drugs: Stimulate muscle fibers by depolarizing the motor end plate
• Anticholinesterase drugs: Inhibit AChE, prolonging ACh action and causing muscle spasm
• Curariform drugs: Block ACh receptors, preventing muscle fiber depolarization and causing paralysis

Myasthenia Gravis

• An autoimmune disease where antibodies attack ACh receptors at the NMJ, leading to muscle weakness
• Anticholinesterase drugs can temporarily improve muscle function

Multi-Unit Smooth Muscle

• Composed of discrete, independent fibers, often innervated by single nerve endings and insulated by a basement membrane
• These fibers are controlled by nerve signals
• Examples include the ciliary muscles of the eye and the piloerector muscles

Unitary Smooth Muscle

• Unitary smooth muscle consists of hundreds to thousands of fibers
• arranged in sheets or bundles
• Connected by gap junctions which allow action potentials to travel from one fiber to the next
• Unitary smooth muscle is found in the walls of most viscera, including the GI tract, bile duct, uterus, and many blood vessels

Smooth Muscle Contraction

• Contains actin and myosin
• Physical organization differs from that of skeletal muscle
• Actin filaments are attached to dense bodies, some of which are attached to the cell membrane and others dispersed inside the cell
• These dense bodies can be bonded to adjacent cells by intracellular protein bridges, which transmit the force of contraction from one cell to the next
• Myosin filaments are interspersed among the actin filaments and have a diameter 5 to 10 times that of actin
• The contractile unit is similar to skeletal muscle but lacks the regularity of skeletal muscle structure Prolonged tonic contraction: Most smooth muscle contraction is prolonged, and lasts hours or even days
• The cycling of myosin cross-bridges is much slower, but the fraction of time the cross-bridges remain attached increases, to a stronger contraction

Low Energy

• Smooth muscle has low energy requirements because of the slow cycling of cross-bridges
• Only one molecule of ATP is required for each cycle, regardless of its duration

Time

• Smooth muscle contraction begins 50 to 100 milliseconds after excitement, reaches full contraction in 0.5 seconds, and then declines in force for 1 to 2 seconds
• Total contraction time = 1 to 3 seconds, which is about 30 times longer than a single skeletal muscle contraction

Force

• Despite having fewer myosin filaments and a slow cycling time, the maximum force of contraction of smooth muscle is often greater than that of skeletal muscle because of the prolonged attachment of myosin cross-bridges

Latch

• Latch Mechanism: Prolonged attachment of myosin to actin filaments, requiring less energy and maintained for extended periods with little excitatory signal

Stress

• Stress Relaxation: Visceral unitary smooth muscle can return to its original force of contraction during elongation or shortening
• When pressure increases, the muscle relaxes to maintain the same pressure, and vice versa (reverse stress relaxation)
• Smooth muscle in the bladder wall relaxes to maintain pressure despite an increase in urinary volume

Stimuli

• The stimulus for smooth muscle contraction is an increase in calcium ion concentration
• which can be caused by nerve stimulation, hormonal stimulation, stretch of the fiber, or changes in the chemical environment
• Smooth muscle doesn’t contain troponin
• Calcium combines with calmodulin to initiate contraction

Intracellulars

• Increased calcium concentration in the cytosol leads to calcium binding to calmodulin
• Calcium binds to calmodulin which activates myosin light chain kinase
• That kinase causes the attachment of the myosin head to the actin filament to causes contraction

Calcium

• Sarcoplasmic Reticulum: Less developed in smooth muscle compared to skeletal muscle
• Dependent: Most calcium ions that cause contraction come from the extracellular fluid
• This causes a delay of 2 to 300 milliseconds

Relaxation

• Smooth muscle contraction is dependent on extracellular calcium ion concentrations
• Relaxation happens when calcium is removed from intracellular fluids by calcium pumps that move calcium ions back into the extracellular fluid or sarcoplasmic reticulum
• The calcium pump is slower than in skeletal muscle, prolonging the contraction duration

Myosin

• Myosin phosphatase causes the myosin head to stop cycling and ceases contraction
• Without myosin phosphatase, contraction would not stop

Nerve Fibers

• Autonomic nerve fibers innervate smooth muscle
• Branch diffusely on top of a sheet of muscle
• Nerve fibers innervate only the outer layer, with excitation traveling to the inner layer via action potential conduction or diffusion of the transmitter

Innervation

• Differs from the motor endplate on skeletal muscle fibers, featuring varicosities in the nerve with interruptions in the Schwann cells
• Nerve vessels contain acetylcholine, norepinephrine, or other substances
• Acetylcholine and norepinephrine are important neurotransmitters
• The effect of these neurotransmitters depends on the receptor, and the effects can vary in different organs Acetylcholine and norepinephrine typically oppose each other and are not released by the same nerve fiber

Local Tissue Factors

• Local factors such as increased hydrogen ion concentration, lack of oxygen, or adenosine can cause contraction and dilation of pre-capillary sphincters, changing blood flow
• Various circulating hormones, including norepinephrine, epinephrine, angiotensin II, endothelin, thromboxane, oxytocin, serotonin, and histamine, affect smooth muscle contraction
• The receptors for these hormones are second messengers, meaning their effects depend on the secondary action of the receptor and can vary in different tissues

Smooth Muscle

• Consists of small fibers from 1 to 5 micrometers in diameter and 20 to