Muscular System: Histology and Physiology (Lesson 9) — Comprehensive Notes

Types of Muscle Tissue and Primary Functions

• Skeletal muscle

  • Responsible for locomotion, facial expressions, posture, respiratory movements, and other body movements

  • Voluntary and controlled by the nervous system

• Smooth muscle

  • Located in walls of hollow organs, blood vessels, eye, glands, skin

  • Functions include: propel urine, mix food in digestive tract, dilating/constricting pupils, regulating blood flow

  • In some locations, autorhythmic

  • Controlled involuntarily by endocrine and autonomic nervous systems

• Cardiac muscle

  • Intact in the heart; major source of movement of blood

  • Autorhythmic

  • Controlled involuntarily by endocrine and autonomic nervous systems

Functions of the Muscular System

1) Movement of the body
2) Maintenance of posture
3) Respiration
4) Production of body heat
5) Communication
6) Constriction of organs and vessels
7) Contraction of the heart

General Properties of Muscle Tissue

• Contractility: ability of a muscle to shorten with force

• Excitability (irritability): capacity to respond to a stimulus (usually from nerves)

• Extensibility: can be stretched beyond resting length and still contract

• Elasticity: ability to recoil to original resting length after stretching

Skeletal Muscle Anatomy and Organization

• Whole skeletal muscle anatomy is organized with connective tissue coverings:

  • Epimysium: dense CT surrounding the whole muscle; merges with fascia between muscles and skin

  • Perimysium: loose CT surrounding a group of muscle fibers called a fascicle; houses blood vessels and nerves

  • Endomysium: loose CT separating individual muscle fibers within each fascicle

  • Collagen from these CT layers merge to form tendons or aponeuroses that attach muscle to bone

• Nerves and blood vessels

  • A motor neuron innervates muscle fibers; one motor neuron can control several fibers

  • An artery and 1–2 veins accompany a nerve through the CT layers

  • Extensive capillary beds surround muscle fibers

Skeletal Muscle Fiber Structure: Key Components

• Skeletal muscle fibers develop from fusion of myoblasts; they are large, multinucleated cells

  • Avg length: $1 ext{–} 4 ext{ mm}$; can reach up to $1 ext{ ft}$ in length

  • Avg diameter: $10 ext{–} 100 \, ext{µm}$

  • Striated appearance

  • Postnatally, the number of fibers is relatively constant; muscles grow via hypertrophy of existing fibers

• Electrical components that respond to and transmit electrical signals:

  • Sarcolemma: the plasma membrane that surrounds sarcoplasm

  • Transverse tubules (T-tubules): inward folds of the sarcolemma that project into the interior of muscle cells

  • Sarcoplasmic reticulum (SR): specialized smooth ER that stores Ca²⁺; enlarged portions are terminal cisternae that lie adjacent to T-tubules; two terminal cisternae plus a T-tubule form a triad

• Mechanical components that enable contraction:

  • Myofibrils: bundles of protein filaments containing the contractile proteins (myofilaments)

  • Myofilaments: actin (thin) and myosin (thick)

  • Myofilaments are arranged into sarcomeres, the basic functional units of muscle fibers and the smallest units that can contract

  • Z-disk: anchor for actin filaments; marks the boundary of a sarcomere

  • Regions of the sarcomere: I band, A band, H zone, M line

  • Titin: elastic filament that contributes to muscle extensibility and elastic recoil

Sarcomere Structure and Filaments

• Actin filaments (thin)

  • Composed of actin monomers (G actin) with active sites that bind to myosin

  • Two strands form a double helix (F actin) with a groove where tropomyosin runs

• Myosin filaments (thick)

  • Golf-club–shaped molecules with a rod portion and two heads

  • Myosin heads bind to actin active sites to form cross-bridges; heads are connected to the rod by a hinge that bends during contraction

  • Myosin heads are ATPases: hydrolyze ATP to provide energy for contraction

• Tropomyosin and Troponin

  • Tropomyosin winds along the groove of the F actin double helix

  • Troponin consists of three subunits: one binds actin, one binds tropomyosin, and one binds calcium (Ca²⁺)

  • Troponin–tropomyosin complex regulates the interaction between actin active sites and myosin heads

• Interaction and cross-bridge cycling

  • Myosin heads bind exposed actin sites to form cross-bridges, then pivot to pull actin filaments toward the center of the sarcomere (power stroke)

  • ATP binds to myosin head; this causes detachment from actin

  • ATP hydrolysis re-cocks the myosin head for another cycle

  • Cross-bridges form, move, detach, and return repeatedly during contraction

• Organization of sarcomeres

  • I band: lighter region containing Z disks and extending to ends of actin

  • A band: central darker region where actin and myosin overlap (except center)

  • H zone: region of the A band where actin and myosin do not overlap

  • M line: middle of the H zone; holds myosin in place

• Cross-bridge cycling energy source

  • ATP hydrolysis provides the energy for the hinge movement of the myosin head

Neuromuscular Junction (NMJ)

• Structure: synapse between a motor neuron and a muscle fiber

  • Presynaptic terminal: axon terminal with synaptic vesicles containing acetylcholine (ACh)

  • Synaptic cleft: the gap between neuron and muscle

  • Postsynaptic membrane (motor end-plate): contains ligand-gated Na⁺ channels

• Transmission sequence (NMJ)

  • Action potentials reach presynaptic terminal and open voltage-gated Ca²⁺ channels

  • Ca²⁺ influx causes vesicles to fuse and release ACh into the synaptic cleft

  • ACh binds to ligand-gated Na⁺ channels on the motor end-plate, opening them and allowing Na⁺ to enter the muscle fiber, depolarizing the postsynaptic membrane

  • If depolarization reaches threshold, an action potential is generated along the sarcolemma

  • ACh is broken down by acetylcholinesterase; choline is reabsorbed and reused to synthesize more ACh

  • The presence of acetate (acetyl groups) relates to glucose metabolism in surrounding cells

• Excitation-contraction coupling follows NMJ activation: electrical signal at the sarcolemma propagates into T-tubules, triggering Ca²⁺ release from SR and initiating contraction

Excitation-Contraction Coupling and the Sliding Filament Mechanism

• Key sequence:
  1) Excitation: action potential generated at NMJ and propagated along sarcolemma and into T-tubules
  2) Calcium release: voltage-sensitive Ca²⁺ channels in the SR terminal cisternae open; Ca²⁺ diffuses into the sarcoplasm
  3) Calcium binding: Ca²⁺ binds to troponin on actin; troponin–troponin–tropomyosin complex shifts to expose actin active sites
  4) Cross-bridge formation: myosin heads bind exposed actin sites to form cross-bridges; power stroke pulls actin toward the center of the sarcomere
  5) Continue cycling: energized myosin heads repeatedly interact with actin as long as Ca²⁺ and ATP are present

• Cross-bridge cycle details

  • Myosin head stores energy from the previous ATP hydrolysis cycle; remains in a high-energy position until stimulated

  • When Ca²⁺ binds and active sites are exposed, the myosin heads bind to actin and perform the power stroke, sliding actin relative to myosin toward the H zone

  • ATP binds to myosin head to detach from actin; ATP is hydrolyzed to ADP and Pi, which re-cocks the head for another cycle

  • In a single contraction, the cross-bridge cycle repeats many times, producing substantial shortening of the sarcomere

• Summary points

  • The interaction and movement of actin and myosin filaments underlie muscle contraction

  • The sarcomere length shortens during contraction as actin filaments slide past myosin; the lengths of thick filaments do not change

  • Calcium handling and energy supply (ATP) are essential for contraction and relaxation

Phases of a Muscle Contraction and Membrane Potentials

• Resting membrane potential and ion channels

  • Inside of the cell is more negative than the outside due to negative proteins and uneven distribution of ions

  • K⁺ leaks out through leak channels, Na⁺ is more concentrated outside; Na⁺/K⁺-ATPase maintains resting potential by moving Na⁺ out and K⁺ in

  • The phospholipid bilayer is hydrophobic and restricts ion movement; transport proteins regulate permeability

• Ligand-gated vs. voltage-gated channels

  • Ligand-gated channels open in response to neurotransmitter binding (e.g., ACh at the NMJ)

  • Voltage-gated channels open/close in response to changes in membrane potential

• Phases of an action potential in muscle fibers

  • Depolarization: Na⁺ channels open; inside becomes positive

  • Repolarization: Na⁺ channels close; K⁺ channels open; inside becomes negative again

  • Hyperpolarization: membrane potential becomes more negative than resting potential due to delayed closing of K⁺ channels

  • The Na⁺/K⁺-ATPase pump returns the membrane to resting potential

• Propagation and all-or-none principle

  • Once threshold is reached, the action potential is propagated across the membrane

  • Action potentials propagate along the membrane and cause adaptation of neighboring regions to trigger new action potentials (not a moving single potential, but successive activations)

• Neuromuscular transmission and subsequent events

  • Action potential at the presynaptic terminal triggers Ca²⁺ influx and ACh release

  • ACh binds to postsynaptic receptors, depolarizing the motor end-plate and triggering an action potential in the muscle fiber

  • ACh is degraded by acetylcholinesterase; choline is reabsorbed for synthesis of new ACh

Action Potential Propagation and Excitation-Contraction Coupling (EC Coupling)

• EC coupling links the action potential to muscle contraction

  • Action potential travels along sarcolemma and into T-tubules

  • Voltage-gated Ca²⁺ channels in terminal cisternae open; Ca²⁺ enters sarcoplasm

  • Ca²⁺ binds troponin; tropomyosin shifts to expose actin sites

  • Cross-bridges form and cycling begins, producing contraction

• Cross-bridge cycling (power stroke and relaxation)

  • Myosin head hydrolyzes ATP (to ADP + Pᵢ) to assume high-energy state

  • When exposed sites are available, myosin binds actin and executes the power stroke

  • ATP binds to myosin to detach from actin; hydrolysis readies head for another cycle

  • Repetition of cycles shortens the sarcomere until Ca²⁺ is removed and relaxation occurs

• Three major ATP-dependent events essential for relaxation
  1) Na⁺/K⁺-ATPase pumps Na⁺ out and K⁺ in to restore resting potential
  2) ATP is required to detach myosin heads from actin (recovery stroke)
  3) Ca²⁺ reuptake into the SR by Ca²⁺-ATPase pumps

Energetics and Heat Production in Skeletal Muscle

• ATP-dependent enzymes critical for contraction

  • Myosin head (ATPase activity)

  • Na⁺/K⁺ pump (to maintain resting membrane potential)

  • Ca²⁺ reuptake pump in the sarcoplasmic reticulum

• ATP production pathways (four processes)

  • Adenylate kinase reaction: $2\,ADP \rightleftharpoons ATP + AMP$

  • Creatine kinase reaction: transfer of phosphate from phosphocreatine to ADP to form ATP

  • Anaerobic respiration: glucose breakdown to yield ATP and lactate in the absence of oxygen

  • Aerobic respiration: requires oxygen; glucose oxidation to ATP, CO₂, and H₂O (more efficient than anaerobic)

• Footnotes on energy use

  • Muscles store limited ATP for about 5$-$6 seconds of contraction; additional ATP must be produced rapidly to sustain activity

Muscle Contraction: Twitch, Tension, and Recruitment

• Muscle Twitch: response of a muscle fiber to a single action potential

  • Phases: Latent (lag) phase, Contraction, Relaxation

• Isometric vs Isotonic contractions

  • Isometric: muscle develops tension without changing length (important for posture)

  • Isotonic: muscle changes length while generating force

• Motor units and recruitment

  • A motor unit is a single motor neuron and all muscle fibers it innervates

  • Large muscles have motor units with many fibers; small muscles have few fibers per unit

  • Strength of contraction is graded by motor unit recruitment and cross-bridge formation

  • Sub-threshold, threshold, submaximal, maximal stimuli regulate recruitment

• Size principle and muscle tone

  • During recruitment, smaller motor units are recruited first, followed by larger ones

  • Muscle tone: constant low-level tension maintained by small periodic contractions across motor units

Isotonic Contractions and Muscle Fiber Types

• Isotonic contraction types

  • Concentric: muscle shortens as it contracts against opposing resistance

  • Eccentric: muscle maintains tension but lengthens as it moves against a greater opposing resistance

• Muscle fiber types

  • Slow-twitch (Type I): slower contraction, smaller diameter, rich in blood supply, more mitochondria, high myoglobin content (dark meat)

  • Fast-twitch (Type II): rapid contraction, higher ATPase activity, less blood supply, fewer and smaller mitochondria, glycolytic capacity (white meat)

  • Subtypes: oxidative vs glycolytic (anaerobic) forms; most muscles have both types in varying proportions; conversion between types is limited

• Exercise effects on muscles

  • Hypertrophy: increase in muscle size due to more myofibrils; increased nuclei from satellite cell fusion; improved strength via better coordination, enzyme production, and circulation; not common to increase fiber number

  • Atrophy: decrease in muscle size; usually reversible except in severe cases where cells die

Training-Related Phenomena: Treppe, Summation, and Tetany

• Treppe (staircase effect): warmer muscles show increased efficiency due to higher enzyme activity and better circulation

• Wave summation: muscle tension increases with higher stimulation frequency

• Incomplete tetanus: partial relaxation between stimuli

• Complete tetanus: no relaxation between stimuli; sustained contraction

• Determinants of force generation: larger diameter fibers tend to generate more force due to more myofibrils and cross-bridges

Force, Tension, and Recruitment Dynamics

• Active tension: force produced during an active contraction; varies with sarcomere length (peak at optimal overlap)

• Passive tension: tension present when a muscle is stretched but not stimulated

• Total tension: sum of active and passive tensions

• Strength of contraction is graded by stimulus strength and motor-unit recruitment

• Size principle applies to recruitment: small motor units activated first, then larger ones as demand increases

• Muscle length at time of contraction influences force generation: over-stretch reduces cross-bridge formation; extreme shortening also limits contraction

Muscle Length-Tension Relationship and Recruitment (Revisited)

• Active tension changes with sarcomere length; optimal overlap yields maximum cross-bridge formation

• Passive tension increases with stretch; total tension depends on both active and passive components

• Recruitment increases force by engaging more motor units; supramaximal stimuli do not further increase force beyond maximal recruitment

Effects of Exercise on Muscle Fiber Size and Metabolism

• Exercise increases metabolic rate and heat production; heat loss via vasodilation and sweating

• Post-exercise oxygen consumption (EPOC): oxygen debt; metabolic processes restore homeostasis after exercise

• Shivering as a mechanism for additional heat production when cold

• Caps and mitochondria adaptations: hypertrophy and enhanced metabolic enzyme production improve endurance and performance

Smooth Muscle: Histology, Physiology, and Regulation

• Location and organization

  • Visceral smooth muscle: cells in sheets forming functional units; many gap junctions; waves of contraction; autorhythmic in some tissues; synapses arranged along branching axons

  • Multiunit smooth muscle: discrete cells or small groups acting as independent units; found in vessels, arrector pili, iris; fewer gap junctions; synapses resemble those in skeletal muscle

• Structural features

  • Not striated; spindle-shaped cells with a single central nucleus

  • Fewer sarcomeres; dense bodies and actin attachments

  • Caveolae in the sarcolemma may act like T-tubules

  • Thick and thin filaments present but not in organized sarcomeres

• Contraction mechanism

  • Ca²⁺ regulation via calmodulin rather than troponin

  • Ca²⁺ binds calmodulin; activates myosin light-chain kinase (MLCK) which phosphorylates myosin heads to initiate contraction

  • Cross-bridge cycling occurs with attached myosin heads; relaxation occurs when myosin phosphatase removes phosphate from myosin

  • Latch state: smooth muscle can sustain tension with low energy expenditure

• Regulation and coordination

  • Regulation by autonomic nervous system and hormones; receptors on smooth muscle can open Na⁺ or Ca²⁺ channels to depolarize or close them to hyperpolarize

  • Visceral smooth muscle contracts as a unit via gap junctions; multiunit smooth muscle contracts as independent units

• Functional properties and responses

  • Slow waves of depolarization/repolarization can propagate through tissue

  • Autonomic innervation modulates contraction; some tissues exhibit autorhythmic activity

  • Receptors respond to various neurotransmitters and hormones (e.g., ACh, norepinephrine, epinephrine, oxytocin, histamine, prostaglandins)

Cardiac Muscle: Structure and Properties

• Found only in the heart; striated and branched fibers

• Each cell typically has one nucleus

• Intercalated disks and gap junctions connect cells, enabling synchronized contraction

• Autorhythmic cells contribute to intrinsic heart rhythm

• Cardiac muscle shares some control with autonomic nervous system but can sustain contraction with high efficiency and automaticity

Aging, Disease, and Special Topics

• Aging effects on skeletal muscle

  • Changes may include reduced muscle mass, altered contractility, and decreased endurance

• Duchenne muscular dystrophy

  • Noted as a muscular disease discussed in relation to skeletal muscle physiology

• Cardiac muscle aging and its implications (brief reference in context)

Key Equations and Concepts (LaTeX)

• Adenylate kinase reaction relevant to ATP production: 2\,ADP \rightleftharpoons ATP + AMP$</p></li><li><p>ATP hydrolysis in the cross-bridge cycle:$ATP \rightarrow ADP + P_i$$

• Cross-bridge cycling and energy considerations rely on ATPase activity of myosin heads

• Na⁺/K⁺-ATPase maintains resting membrane potential; key for action potential generation and propagation

• Calcium handling: Ca²⁺ release from SR, Ca²⁺ binding to troponin, exposure of actin active sites, and subsequent cross-bridge cycling

Quick Reference: Major Concepts to Remember

• Three key ATP-dependent enzymes in skeletal muscle function

  • Myosin head ATPase

  • Na⁺/K⁺-ATPase pump

  • Ca²⁺-ATPase pump in the SR

• Major sarcomere structures (I band, A band, Z disk, M line, H zone) and filament types (actin, myosin)

• Mechanism of excitation-contraction coupling from NMJ to contraction

• Distinctions among muscle types (skeletal, smooth, cardiac) and their regulatory mechanisms

• Phases of muscle contraction, including twitch phases and recruitment dynamics

• Effects of exercise on muscle: hypertrophy, fatigue mechanisms, oxygen debt, and heat production

• Distinctions between visceral vs multiunit smooth muscle and their regulatory patterns

• Aging and disease notes relevant to muscle function (e.g., Duchenne muscular dystrophy)

Glossary of Top Terms

• Epimysium, Perimysium, Endomysium

• Sarcolemma, T-tubules, Sarcoplasmic Reticulum, Terminal Cisternae, Triad

• Myofibril, Myofilaments (Actin, Myosin), Sarcomere, Z disk, I band, A band, H zone, M line

• Titin, Tropomyosin, Troponin

• Neuromuscular Junction (presynaptic terminal, synaptic cleft, postsynaptic membrane)

• Action Potential, Resting Membrane Potential, Na⁺/K⁺-ATPase

• Ligand-gated vs Voltage-gated ion channels

• Cross-bridge, Power stroke, Recovery stroke

• Treppe, Wave summation, Tetany, Isotonic vs Isometric contractions

• Type I (Slow-twitch) and Type II (Fast-twitch) fibers

• Hypertrophy, Atrophy, Oxygen debt (EPOC)

• Smooth muscle (Visceral vs Multiunit), Calmodulin, MLCK, Myosin phosphatase

• Cardiac muscle, Intercalated disks, Autorhythmicity