Chapter 10 Muscle Tissue Anatomy & Physiology

Chapter 10: Muscle Tissue Anatomy & Physiology: An Integrative Approach

10.1 Skeletal Muscle: Functions and Characteristics

Functions of Skeletal Muscle

Skeletal muscle is a specialized tissue that performs five major functions vital for homeostasis and daily activity:

Body Movement: Muscles move bones to allow for locomotion, facial expressions, speech, breathing, and swallowing.
Maintenance of Posture: Skeletal muscles stabilize joints and help maintain body positions against gravity.
Protection and Support: Muscle packages internal organs and holds them in place to prevent injury or displacement.
Regulation of Material Elimination: Circular sphincters control the passage of material at various body orifices.
Heat Production: Muscle activity helps maintain body temperature by releasing energy as heat during contraction.

Characteristics of Skeletal Muscle Tissue

Muscle tissue possesses five fundamental characteristics that enable its function:

Excitability: The ability of muscle cells to respond to a stimulus (usually local neurotransmitter release) by changing their electrical membrane potential.
Conductivity: Involves sending an electrical change (an action potential) down the length of the cell membrane.
Contractility: Exhibited when protein filaments slide past each other, enabling the muscle to shorten and cause movement.
Extensibility: The ability of the muscle to be stretched.
Elasticity: The ability of the muscle to return to its original length following a lengthening or shortening event.

10.2 Anatomy of Skeletal Muscle

Gross Anatomy: Connective Tissue Components

A skeletal muscle is considered an organ because it consists of multiple tissue types, including skeletal muscle fibers, connective tissue, blood vessels, and nerves. The organization follows a hierarchical structure wrapped in three concentric layers of connective tissue:

Epimysium: A layer of dense irregular connective tissue that wraps the entire whole muscle.
Perimysium: A layer of dense irregular connective tissue that wraps a fascicle (a bundle of muscle fibers). It houses primary blood vessels and nerves.
Endomysium: A delicate layer of areolar connective tissue that wraps an individual muscle fiber. It provides electrical insulation, capillary support, and binds neighboring cells.

Attachments and Fascia

Muscles attach to bone, skin, or other muscles via specialized structures:

Tendon: A cordlike structure composed of dense regular connective tissue.
Aponeurosis: A thin, flattened sheet of dense irregular tissue.
Deep Fascia: Dense irregular connective tissue located superficial to the epimysium. It separates individual muscles and binds together those with similar functions.
Superficial Fascia: Composed of areolar and adipose connective tissue superficial to the deep fascia. It separates muscles from the skin.

Blood Vessels and Nerves

Vascularization: Skeletal muscle is highly vascularized to deliver oxygen and nutrients and remove metabolic waste products.
Innervation: Muscle is innervated by somatic motor neurons. The axons of these neurons branch and terminate at neuromuscular junctions. Contraction is consciously controlled, making it a voluntary muscle.

Microscopic Anatomy of a Muscle Fiber

Skeletal muscle fibers have several unique specializations:

Multinucleated Development: Individual cells are formed in the embryo when multiple myoblasts fuse. Some myoblasts remain as undifferentiated satellite cells for support and repair.
Sarcolemma and T-tubules: The sarcolemma (plasma membrane) contains voltage-gated ion channels. It has transverse tubules (T-tubules) that extend deep into the cell, containing voltage-sensitive calcium channels.
Sarcoplasm: The cytoplasm contains typical organelles plus contractile proteins and other specializations.
Sarcoplasmic Reticulum (SR): An internal membrane complex similar to smooth ER. It includes terminal cisternae (blind sacs) that serve as calcium reservoirs.
- Triad: A combination of two terminal cisternae with a T-tubule in between.
- Calcium Management: The SR contains calcium pumps that import $Ca^{2+}$ into the SR, where it binds to proteins like calmodulin and calsequestrin. The SR also contains calcium release channels triggered by electrical signals.

Myofilaments and the Sarcomere

Myofibrils are bundles of myofilaments. There are two primary types:

Thick Filaments: Bundles of $200\text{--}500$ myosin protein molecules. Myosin heads (which contain myosin ATPase) point toward the ends of the filament.
Thin Filaments: Composed of twisted strands of actin. Each F-actin strand is made of G-actin monomers, which have myosin binding sites. Regulatory proteins include tropomyosin and troponin.

Sarcomere Organization

Sarcomeres are repeating functional units delineated by Z discs:

Z discs: Specialized proteins perpendicular to myofilaments that anchor thin filaments.
I bands: Light regions containing only thin filaments; they bisect the Z discs and narrow during contraction.
A band: Dark central region containing thick filaments and overlapping thin filaments.
H zone: Central portion of the A band containing only thick filaments; it disappears with maximal contraction.
M line: The middle of the H zone; a protein meshwork that anchors thick filaments.

Structural and Functional Proteins

Connectin: Extends from Z disc to M line, stabilizing thick filaments and providing passive tension (springlike properties).
Dystrophin: Anchors myofibrils to sarcolemma proteins.
Nebulin: Functions in sarcomere assembly and cross-bridge cycling; anchored to the Z disc.

Energy and Storage Components

Muscle fibers require significant energy for contraction:

Mitochondria: Abundant for aerobic $ATP$ production.
Myoglobin: A molecule within the cell that stores oxygen for aerobic metabolism.
Glycogen: Stored for quick fuel access.
Creatine Phosphate: Provides a quick phosphate source to replenish $ATP$ .

10.3 Physiology of Muscle Contraction

The Motor Unit

A motor unit consists of a single motor neuron and all the muscle fibers it controls. The size of the unit varies:

Small Motor Units: Less than five muscle fibers (for precise control).
Large Motor Units: Thousands of muscle fibers (for large force production).
Distribution: Fibers of a unit are dispersed throughout the muscle rather than clustered.

The Neuromuscular Junction (NMJ)

The NMJ is the site where the motor neuron innervates the muscle fiber. Key components include:

Synaptic Knob: The expanded tip of the axon housing synaptic vesicles filled with acetylcholine ( $ACh$ ). It features voltage-gated $Ca^{2+}$ channels and calcium pumps.
Motor End Plate: A folded region of the sarcolemma with many $ACh$ receptors (chemically gated ion channels).
Synaptic Cleft: The fluid-filled space between the knob and the end plate. It contains acetylcholinesterase, which breaks down $ACh$ .

Resting Membrane Potential (RMP)

At rest, a muscle fiber exhibits an RMP of approximately $-90\,mV$ . This is established by leak channels and $Na^+/K^+$ pumps, with voltage-gated channels closed.

Events of Muscle Contraction

Muscle contraction involves a series of sequential events:

1. Excitation at the NMJ

A nerve signal opens voltage-gated $Ca^{2+}$ channels in the synaptic knob.
$Ca^{2+}$ enters the knob and triggers the exocytosis of $ACh$ (about $300$ vesicles).
$ACh$ diffuses across the cleft and binds to receptors on the motor end plate.

2. Excitation-Contraction Coupling

End-Plate Potential (EPP): Bound $ACh$ causes receptors to open; $Na^+$ diffuses in rapidly while $K^+$ diffuses out slowly. The RMP changes from $-90\,mV$ to $-65\,mV$ (threshold).
Action Potential (AP): Opening of adjacent voltage-gated $Na^+$ channels causes depolarization (to $+30\,mV$ ). Opening of voltage-gated $K^+$ channels causes repolarization ( $K^+$ moves out) to return to $-90\,mV$ .
Propagation: The AP travels down the sarcolemma into T-tubules, reaching the triad.
Calcium Release: The electrical signal triggers voltage-sensitive calcium channels in the T-tubule to stimulate $Ca^{2+}$ release channels in the SR. $Ca^{2+}$ enters the sarcoplasm.

3. Crossbridge Cycling

Once $Ca^{2+}$ is released, four steps repeat to shorten the sarcomere:

Crossbridge Formation: $Ca^{2+}$ binds to troponin, moving the troponin-tropomyosin complex and exposing actin binding sites. The myosin head attaches to actin.
Power Stroke: The myosin head swivels toward the center of the sarcomere, pulling the thin filament. $ADP$ and $P_i$ are released.
Release of Myosin Head: A new $ATP$ molecule binds to the myosin head, causing it to detach from actin.
Reset Myosin Head: Myosin ATPase splits $ATP$ into $ADP$ and $P_i$ , providing energy to "cock" the head into its ready position.

Sliding Filament Theory: Thick and thin filaments slide past each other without changing length, resulting in a narrowed H zone and I band and shortened sarcomere.

Muscle Relaxation

Relaxation requires the reversal of contraction steps:

Termination of nerve signals and hydrolysis of $ACh$ by acetylcholinesterase.
Closure of $ACh$ receptors and cessation of the action potential.
$Ca^{2+}$ is pumped back into the SR terminal cisternae.
Troponin returns to its original shape, and tropomyosin moves to re-block actin binding sites.
Elasticity helps return the muscle to its original position.

10.4 Muscle Metabolism and Energy Supply

Sources of ATP

Muscle cells store only enough $ATP$ for approximately $5$ seconds of intense exertion. Additional energy is generated via:

Phosphate Transfer System:
- Myokinase: Transfers phosphate from one $ADP$ to another to make $ATP$ .
- Creatine Phosphate: Catalyzed by creatine kinase; provides an additional $10\text{--}15$ seconds of energy.
Glycolysis: Anaerobic process in the cytosol. Converts glucose (from glycogen or blood) into two pyruvate, releasing $2\,ATP$ per glucose.
Aerobic Cellular Respiration: Occurs in mitochondria. Oxidizes pyruvate, fatty acids, and amino acids. Produces much larger amounts of $ATP$ but at a slower rate.

Lactate and Exercise Intensity

Lactate Formation: Occurs when oxygen is low; pyruvate is converted to lactate by lactate dehydrogenase.
Lactic Acid Cycle: Lactate travels to the liver, is converted to glucose, and returns to the muscle.
Exercise Duration:
- Sprints ( $<10$ seconds): Phosphate transfer system.
- $400\text{-meter}$ sprint: Glycolysis.
- $1600\text{-meter}$ run: Aerobic cellular respiration.

Oxygen Debt

Oxygen debt is the extra oxygen required after exercise to:

Replace oxygen on hemoglobin and myoglobin.
Replenish glycogen, $ATP$ , and creatine phosphate.
Convert lactic acid back into glucose.

10.5 Skeletal Muscle Fiber Types

Fibers are classified based on contraction speed/power and their means of supplying $ATP$ :

Slow Oxidative (SO) (Type I): Slower, less powerful, but high endurance. Red in color (high myoglobin) and half the diameter of others.
Fast Oxidative (FO) (Type IIa): Fast, powerful, primarily aerobic. Intermediate size and light red color.
Fast Glycolytic (FG) (Type IIx): Fast, powerful, brief contractions. Anaerobic, largest size, and white in color (lack of myoglobin).

Distribution: Most muscles contain a mixture. Hand muscles have high FG fibers; back muscles have high SO fibers for posture. Distribution is primarily genetic but influenced by training.

10.6 Muscle Tension and Stimulation

The Muscle Twitch

A twitch is a single response to a single stimulus at threshold voltage:

Latent Period: Time before contraction; no tension change.
Contraction Period: Tension increases as power strokes occur.
Relaxation Period: Tension decreases as crossbridges release.

Stimulation Dynamics

Recruitment (Multiple Motor Unit Summation): Increasing stimulus intensity recruits more motor units (small units first). Above peak voltage, maximum contraction occurs.
Wave Summation (Temporal Summation): Increasing stimulus frequency ( $20\text{--}50$ per second). Relaxation is incomplete, and forces add up.
Incomplete Tetany: Twitches partially fuse.
Tetany: Smooth line of tension without relaxation (at frequencies like $40\text{--}50$ per second). Prolonged tetany leads to fatigue.

10.7 Contraction Types and Properties

Muscle Tone

Involuntary nervous stimulation creates resting tension (muscle tone). Motor units are stimulated randomly to avoid fatigue without causing movement. Tone decreases during deep sleep.

Isometric vs. Isotonic Contraction

Isometric Contraction: Tension is generated, but resistance is not overcome; muscle length remains constant.
Isotonic Contraction: Resistance is overcome; length changes while tone stays constant.
- Concentric: Muscle shortens.
- Eccentric: Muscle lengthens.

Length-Tension Relationship

The force of contraction depends on fiber length at the time of stimulation:

Resting Length: Maximum force (optimal filament overlap).
Shortened/Extended Length: Weaker force due to limited movement or minimal overlap.

Muscle Fatigue

Primarily caused by decreased glycogen stores. Other causes include:

Insufficient $Ca^{2+}$ in synaptic knob.
Altered ion concentrations affecting the Action Potential.
Excessive $P_i$ slowing $Ca^{2+}$ release or crossbridge cycling.

10.8 Exercise, Aging, and Health

Effects of Exercise and Aging

Hypertrophy: Increase in muscle size due to synthesis of contractile proteins, mitochondria, and glycogen stores. Results from resistance training.
Hyperplasia: Limited increase in the number of muscle fibers.
Atrophy: Decrease in size due to lack of use; reversible initially but can become permanent.
Aging: Slow loss of mass begins in mid- $30s$ . Includes decreased fiber size/number, loss of myofibrils, reduced oxygen storage, and fibrosis (replacement with dense regular connective tissue).

10.9 Cardiac and Smooth Muscle Tissue

Cardiac Muscle

Short, branching fibers with one or two nuclei and striations.
Intercalated Discs: Contain desmosomes and gap junctions to join fibers.
Control: Started by autorhythmic pacemaker cells; influenced by the autonomic nervous system ( $ANS$ ).

Smooth Muscle

Location: Found in blood vessels, bronchioles, intestines, ureters, and the uterus.
Structure: Fusiform shape (no striations/Z discs). Sarcolemma has caveolae (invaginations). Cytoskeleton includes intermediate filaments, dense bodies, and dense plaques.
Mechanism of Contraction:
- $Ca^{2+}$ enters from interstitial fluid and binds to calmodulin.
- The complex activates myosin light-chain kinase (MLCK).
- MLCK phosphorylates the myosin head to trigger crossbridge cycling.
- Myosin light-chain phosphatase is required for relaxation.
Latchbridge Mechanism: Myosin attaches to actin for extended periods without extra $ATP$ .
Functional Categories:
- Multiunit: Stimulated individually (e.g., iris, arrector pili).
- Single-unit: Stimulated in unison via gap junctions (most common in hollow organs).

Clinical Views

Muscular Dystrophy: Degenerative diseases; Duchenne muscular dystrophy (DMD) involves defective dystrophin, leading to sarcolemma damage and muscle atrophy by age $30$ .
Myasthenia Gravis: Autoimmune disease where antibodies block $ACh$ receptors, causing weakness and fatigue.
Tetanus: Spastic paralysis caused by Clostridium tetani toxin; blocks inhibitory neurotransmitters.
Botulism: Paralysis caused by Clostridium botulinum toxin; prevents $ACh$ release.
Anabolic Steroids: Synthetic testosterone mimics; stimulate protein synthesis but carry risks like heart disease, liver damage, and reproductive issues.

Review and Discussion

What are the five functions of muscle? Movement, posture, protection, regulation, heat.
Compare contractility, extensibility, and elasticity? Contractility is shortening; extensibility is stretching; elasticity is returning to length.
What are the structures from largest to smallest? Whole muscle, fascicle, muscle fiber, myofibril, myofilament, sarcomere.
Why do motor units vary? Smaller units allow for precision; larger units allow for force.
What triggers exocytosis of $ACh$ ? Calcium entry into the synaptic knob.
What causes myosin head release? $ATP$ binding.
What is oxygen debt? The extra oxygen needed post-exercise to restore homeostatic levels of nutrients and gases.