MUSCULAR SYSTEM

1. Overview of Muscle Tissue

1.1 Types of Muscle Tissue

1.2 Functions of Skeletal Muscle

1. Movement — locomotion, manipulation, expression

2. Posture and stability — continuous low-level contractions maintain position

3. Joint stabilisation — dynamic support across joints

4. Heat production — ~85% of body heat from muscle metabolism; shivering thermogenesis

5. Protection — abdominal muscles protect viscera

6. Storage — amino acid reservoir; glycogen storage

7. Metabolic regulation — glucose uptake; insulin sensitivity

2. Skeletal Muscle Structure (Macro to Micro)

2.1 Organisational Hierarchy

MUSCLE (whole organ)
    ↓
FASCICLE (bundle of fibres)
    ↓
MUSCLE FIBRE (single cell)
    ↓
MYOFIBRIL (contractile strand)
    ↓
SARCOMERE (functional unit)
    ↓
MYOFILAMENTS (actin & myosin)

2.2 Connective Tissue Layers

All three layers converge at the ends of the muscle to form tendons (cord-like) or aponeuroses (sheet-like), which attach muscle to bone via Sharpey's fibres.

2.3 Muscle Fibre (Cell) Structure

Sarcolemma

• Plasma membrane of muscle fibre

• Contains ion channels (Na⁺, K⁺, Ca²⁺) for action potentials

• Invaginates to form T-tubules

T-Tubules (Transverse Tubules)

• Deep invaginations of sarcolemma

• Conduct action potentials into fibre interior

• Ensure simultaneous activation of all myofibrils

• Located at A-I band junction in skeletal muscle

Sarcoplasm

• Cytoplasm of muscle fibre

• Contains glycogen granules, myoglobin, mitochondria

• High concentration of enzymes for ATP production

Sarcoplasmic Reticulum (SR)

• Specialised smooth ER

• Network surrounds each myofibril

• Primary function: Ca²⁺ storage and release

• Terminal cisternae — enlarged ends adjacent to T-tubules

• Triad: 2 terminal cisternae + 1 T-tubule

Myofibrils

• Cylindrical organelles running length of fibre

• Composed of sarcomeres in series

• Occupy ~80% of fibre volume

• Responsible for striated appearance

Mitochondria

• Located between myofibrils and beneath sarcolemma

• Abundant in oxidative fibres

• Produce ATP via aerobic metabolism

Myoglobin

• Oxygen-binding protein (similar to haemoglobin)

• Stores oxygen within muscle

• Higher concentration in slow-twitch fibres → red colour

• Facilitates oxygen diffusion to mitochondria

Satellite Cells

• Located between sarcolemma and basal lamina

• Quiescent stem cells

• Activated by muscle damage or exercise

• Proliferate and fuse with existing fibres → hypertrophy

• Donate nuclei to support increased protein synthesis

• Crucial for muscle repair and adaptation

2.4 The Sarcomere

Definition: The functional (contractile) unit of muscle, spanning from one Z-line to the next.

Components and Bands

Mnemonic: "Hides In contraction" — H-zone and I-band shorten; A-band stays constant.

2.5 Myofilaments

Thick Filaments (Myosin)

Structure

• ~300 myosin molecules per thick filament

• Each myosin molecule has:

  • Tail: two intertwined heavy chains (α-helix)

  • Heads (cross-bridges): two globular heads per molecule

• Heads project at regular intervals (every 14.3 nm, 60° apart)

• Bare zone at centre (M-line region) — no heads

Myosin Head Properties

• Actin-binding site: attaches to thin filament

• ATPase site: hydrolyses ATP → provides energy for power stroke

• Flexible hinge regions: allow head movement

Myosin Isoforms

• Myosin Heavy Chain (MHC) determines contractile properties

• MHC I (slow), MHC IIa (fast oxidative), MHC IIx (fast glycolytic)

• Different ATPase activity → different contraction speeds

Thin Filaments (Actin + Regulatory Proteins)

Actin

• G-actin (globular) monomers polymerise into F-actin (filamentous)

• Two F-actin strands twisted into helix

• Each G-actin has myosin-binding site

• ~360 actin monomers per thin filament

Tropomyosin

• Long, rod-shaped protein

• Lies in groove between F-actin strands

• Each molecule spans ~7 actin monomers

• Function: Blocks myosin-binding sites at rest

Troponin Complex

• Globular protein attached to tropomyosin (every 7 actins)

• Three subunits:

  • TnC (Troponin C): Binds Ca²⁺ (trigger for contraction)

  • TnI (Troponin I): Inhibits actin-myosin interaction

  • TnT (Troponin T): Binds troponin complex to tropomyosin

2.6 Structural Proteins

Clinical Note: Dystrophin mutations cause Duchenne/Becker muscular dystrophy — progressive muscle weakness due to membrane instability.

3. Muscle Fibre Types

3.1 Classification Systems

Historical Names:

• Red vs White (based on colour)

• Slow-twitch vs Fast-twitch (based on contraction speed)

• Oxidative vs Glycolytic (based on metabolism)

Modern Classification (based on Myosin Heavy Chain isoform):

• Type I (MHC I)

• Type IIa (MHC IIa)

• Type IIx (MHC IIx) — previously called Type IIb in humans

3.2 Detailed Fibre Type Comparison

3.3 Metabolic Characteristics

Type I Fibres — Oxidative Metabolism

• High mitochondrial volume (up to 10% of fibre volume)

• Extensive capillary network (~5-6 capillaries per fibre)

• Rely on fatty acid oxidation + glucose oxidation

• Efficient ATP production (36-38 ATP per glucose)

• Sustained activity possible for hours

Type IIa Fibres — Mixed Metabolism

• Good mitochondrial density

• Adequate capillary supply

• Can use both aerobic and anaerobic pathways

• Versatile — adapt to training stimulus

• Sustained for moderate durations

Type IIx Fibres — Glycolytic Metabolism

• Few mitochondria

• Limited capillary supply

• Rely on phosphocreatine and anaerobic glycolysis

• Rapid ATP production but limited capacity

• Fatigue quickly (lactate accumulation, PCr depletion)

3.4 Fibre Type Distribution

Genetic Determination

• Fibre type proportions largely inherited (~45-50% heritability)

• Distribution established early in development

• Average person: ~50% Type I, ~35% Type IIa, ~15% Type IIx

• Wide individual variation (25-75% Type I)

Muscle-Specific Distribution

Elite Athlete Distribution

3.5 Fibre Type Plasticity

What CAN Change

• Type IIx ↔ Type IIa conversion readily occurs

• Endurance training: IIx → IIa (increased oxidative capacity)

• Detraining/immobilisation: IIa → IIx

• Metabolic enzyme concentrations highly adaptable

• Mitochondrial density can increase 40-100%

• Capillary density increases with endurance training

What is DIFFICULT to Change

• Type I ↔ Type II conversion very limited

• Requires extreme stimulus (chronic low-frequency stimulation, spinal cord injury)

• Some evidence of I → IIa with explosive training, but controversial

• Myosin heavy chain isoform expression resistant to change

Hybrid Fibres

• Fibres expressing multiple MHC isoforms (e.g., I/IIa, IIa/IIx)

• More common than "pure" fibre types

• Proportion changes with training

• May represent transitional states

3.6 Fibre Types and Sport Performance

Endurance Sports (Favour Type I)

• Marathon, triathlon, distance cycling, cross-country skiing

• High VO₂max correlation with Type I %

• Training enhances oxidative capacity of all fibres

Power/Sprint Sports (Favour Type II)

• Sprinting, jumping, throwing, weightlifting

• Peak power output correlates with Type II %

• Neural factors and IIa percentage trainable

Mixed Sports

• Team sports, middle-distance, combat sports

• Benefit from both fibre types

• Periodised training addresses multiple qualities

4. Muscle Actions: Agonist, Antagonist, Synergist, Fixator

4.1 Definitions and Roles

Agonist (Prime Mover)

• Muscle primarily responsible for producing a movement

• Contracts concentrically to create joint motion

• Example: Biceps brachii during elbow flexion

Antagonist

• Muscle that opposes the agonist's action

• Located on opposite side of joint

• Functions:

  • Relaxes to allow movement (reciprocal inhibition)

  • Eccentrically controls movement speed (braking)

  • Co-contracts with agonist for joint stability

• Example: Triceps brachii during elbow flexion

Synergist

• Muscle that assists the agonist

• May:

  • Add force in same direction

  • Stabilise intermediate joints

  • Neutralise unwanted actions of agonist

• Example: Brachialis and brachioradialis assist biceps in elbow flexion

Fixator (Stabiliser)

• Muscle that stabilises the origin of the agonist

• Prevents unwanted movement at proximal joints

• Allows efficient force transfer

• Example: Rotator cuff stabilises shoulder during biceps curl

Neutraliser

• Special type of synergist

• Cancels out unwanted secondary action of agonist

• Example: Pronator teres neutralises supination tendency of biceps

4.2 Muscle Role Reversal

Roles are Context-Dependent

• Same muscle can be agonist, antagonist, synergist, or fixator depending on:

  • Movement being performed

  • Body position

  • External load

  • Movement velocity

Example: Rectus Femoris

4.3 Co-Contraction (Co-Activation)

Definition: Simultaneous activation of agonist and antagonist muscles

Functions

• Increases joint stiffness and stability

• Protects joints during unpredictable movements

• Essential for precision movements

• Higher in novices; decreases with skill acquisition

Examples

• Knee co-contraction during landing (quadriceps + hamstrings)

• Trunk co-contraction during lifting (abs + erectors)

• Wrist co-contraction during striking (flexors + extensors)

Trade-Offs

• Increased stability but decreased movement efficiency

• Higher metabolic cost

• Reduced net joint torque and velocity

4.4 Force Couples

Definition: Two or more muscles acting on different parts of a segment to produce rotation

Examples

Upward Rotation of Scapula

• Upper trapezius (pulls acromion up)

• Lower trapezius (pulls medial spine down)

• Serratus anterior (pulls inferior angle laterally)

• Together: rotate glenoid upward for arm elevation

Posterior Pelvic Tilt

• Rectus abdominis (pulls pubic symphysis up anteriorly)

• Gluteus maximus (pulls posterior pelvis down)

• Together: rotate pelvis posteriorly

Anterior Pelvic Tilt

• Hip flexors (pull pelvis forward/down)

• Erector spinae (pull posterior pelvis up)

• Together: rotate pelvis anteriorly

4.5 Reciprocal Inhibition

Definition: When agonist contracts, antagonist is neurologically inhibited

Mechanism

1. Motor neuron activates agonist

2. Ia afferent from muscle spindle synapses with inhibitory interneuron

3. Interneuron inhibits antagonist motor neuron

4. Antagonist relaxes

Significance

• Allows smooth, efficient movement

• Prevents muscle working against itself

• Can be overridden (co-contraction)

• Used in PNF stretching techniques

4.6 Practical Applications by Joint

Elbow Flexion Example

Knee Extension (Kicking) Example

Hip Extension (Running) Example

5. Sliding Filament Theory of Muscle Contraction

5.1 Historical Development

• 1954: Huxley & Hanson and Huxley & Niedergerke independently proposed

• Observed: sarcomere shortening occurs without filament shortening

• A-band remains constant; I-band and H-zone decrease

• Conclusion: filaments must slide past each other

5.2 The Sliding Filament Mechanism (Overview)

1. Thin filaments slide toward M-line

2. Thick filaments remain stationary

3. Z-lines pulled closer together

4. Sarcomere shortens

5. No change in filament lengths themselves

5.3 Cross-Bridge Cycle (Detailed Steps)

Prerequisites

• ATP present (bound to myosin head)

• Ca²⁺ released from SR

• Troponin-tropomyosin shifted to expose binding sites

Step 1: Cross-Bridge Formation (Attachment)

• Myosin head (energised, cocked position) binds to exposed actin binding site

• Forms actomyosin cross-bridge

• ADP and Pᵢ still bound to myosin

Step 2: Power Stroke

• Pᵢ released from myosin head

• Conformational change in myosin head

• Head pivots ~45° toward M-line

• Thin filament pulled toward centre of sarcomere

• ADP released at end of power stroke

• Force generated: ~2-4 pN per cross-bridge; distance: ~10 nm

Step 3: Cross-Bridge Detachment

• New ATP molecule binds to myosin head

• Causes conformational change that releases myosin from actin

• ATP binding is essential for detachment

• Rigor mortis: no ATP → cross-bridges remain attached → muscle stiffness

Step 4: Myosin Reactivation (Recovery Stroke)

• ATP hydrolysed to ADP + Pᵢ (both remain bound)

• Energy released stored in myosin head

• Head returns to cocked (energised) position

• Ready for next cycle if Ca²⁺ still present and binding sites exposed

Cycle Summary

Attachment → Power Stroke → Detachment → Recovery → Attachment...

Cycle Characteristics

• Each cycle shortens sarcomere ~10 nm (1% of sarcomere length)

• Cycle rate: ~5/sec (slow fibres) to ~50/sec (fast fibres)

• Many cycles needed for significant shortening

• Asynchronous cycling — not all cross-bridges in same phase simultaneously

5.4 Regulation of Contraction: The Role of Calcium

At Rest (Low [Ca²⁺])

• Ca²⁺ sequestered in SR (~10,000× higher than sarcoplasm)

• Sarcoplasmic [Ca²⁺] ≈ 0.1 μM

• Tropomyosin covers actin binding sites

• Troponin I inhibits interaction

• No cross-bridges can form

During Contraction (High [Ca²⁺])

• Ca²⁺ released into sarcoplasm

• Sarcoplasmic [Ca²⁺] rises to ~10 μM

• Ca²⁺ binds to Troponin C (4 Ca²⁺ per troponin)

• Conformational change in troponin complex

• Tropomyosin shifts deeper into actin groove

• Myosin binding sites exposed

• Cross-bridge cycling occurs

Relaxation

• Ca²⁺ actively pumped back into SR by SERCA pumps

• Requires ATP (1 ATP per 2 Ca²⁺)

• [Ca²⁺] drops below threshold

• Ca²⁺ dissociates from TnC

• Tropomyosin returns to blocking position

• Cross-bridges cannot form

• Muscle relaxes

5.5 Excitation-Contraction Coupling

Definition: The sequence of events linking action potential to muscle contraction

Step-by-Step Process

1. Action potential arrives at neuromuscular junction

   • Motor neuron releases acetylcholine (ACh)

2. ACh binds to receptors on motor end plate

   • Nicotinic receptors on sarcolemma

   • Na⁺ influx → end-plate potential

3. Action potential generated on sarcolemma

   • Threshold reached → voltage-gated Na⁺ channels open

   • AP propagates along sarcolemma (~5 m/s)

4. AP travels down T-tubules

   • T-tubules conduct AP deep into fibre

   • Ensures all myofibrils activated simultaneously

5. Voltage-gated Ca²⁺ channels (DHPR) activated

   • Dihydropyridine receptors on T-tubule membrane

   • Detect voltage change

6. SR Ca²⁺ release channels (RyR) open

   • Ryanodine receptors on SR membrane

   • Mechanical coupling (skeletal) or Ca²⁺-induced Ca²⁺ release (cardiac)

   • Ca²⁺ floods into sarcoplasm

7. Ca²⁺ binds to Troponin C

   • Tropomyosin-troponin shift

   • Actin binding sites exposed

8. Cross-bridge cycling occurs

   • Contraction proceeds as long as Ca²⁺ elevated and ATP available

9. Ca²⁺ reuptake by SERCA

   • ATP-dependent Ca²⁺ pumps

   • [Ca²⁺] returns to resting levels

10. Relaxation

    • Troponin-tropomyosin block binding sites

    • Cross-bridges detach

    • Muscle returns to resting length (if no load)

5.6 ATP in Muscle Contraction

ATP is Required For:

1. Cross-bridge detachment

   • ATP binding causes myosin release from actin

   • Without ATP → rigor (permanent attachment)

2. Myosin head energisation

   • ATP hydrolysis cocks the myosin head

   • Stores energy for power stroke

3. Ca²⁺ reuptake

   • SERCA pumps use 1 ATP per 2 Ca²⁺

   • Necessary for relaxation

4. Na⁺/K⁺ pump

   • Restores ion gradients after action potential

   • Maintains excitability

ATP Turnover in Muscle

• Resting muscle: ~1-2 μmol/g/min

• Maximal exercise: ~150-300 μmol/g/min (100-150× increase)

• Muscle ATP stores last only ~2-3 seconds at max intensity

• Continuous regeneration essential (PCr, glycolysis, oxidative)

5.7 Length-Tension Relationship

Principle: Force production depends on sarcomere length (degree of actin-myosin overlap)

Physiological Implications

• Joint angle affects muscle force output

• Muscles have optimal joint angles for force

• Example: Biceps strongest at ~90° elbow flexion

• Pre-stretch (eccentric before concentric) optimises sarcomere length

Active vs Passive Tension

• Active tension: Generated by cross-bridge cycling

• Passive tension: Generated by elastic elements (titin, connective tissue)

• Total tension = Active + Passive

• At very long lengths, passive tension compensates for reduced active tension

5.8 Force-Velocity Relationship

Concentric Contraction (Shortening)

• As velocity increases, force decreases (inverse relationship)

• At maximum velocity (Vmax), force ≈ 0

• At zero velocity (isometric), force is maximal

Eccentric Contraction (Lengthening)

• As velocity increases, force can increase (up to ~1.5-2× isometric max)

• Cross-bridges forcibly detached

• More cross-bridges attached at any instant

Isometric Contraction

• No change in muscle length

• Velocity = 0

• Maximum isometric force (P₀)

Hill's Equation (P + a)(V + b) = (P₀ + a)b

Where P = force, V = velocity, P₀ = maximum isometric force, a and b are constants

Power Output

• Power = Force × Velocity

• Maximum power at ~30% Vmax and ~30% P₀

• Important for explosive movements (jumping, sprinting)

Fibre Type Differences

• Type II fibres: Higher Vmax, higher power output

• Type I fibres: Lower Vmax, but more fatigue-resistant

6. Types of Muscle Contraction

6.1 Classification by Length Change

6.2 Concentric Contraction

Mechanics

• Muscle force > external resistance

• Cross-bridges perform work

• Sarcomeres shorten

• Z-lines move closer

Characteristics

• Force decreases as velocity increases

• ATP used for power strokes

• Primary mode for generating movement

• Examples: lifting, pushing, throwing

6.3 Eccentric Contraction

Mechanics

• External force > muscle force

• Muscle lengthens despite activation

• Cross-bridges forcibly broken

• "Braking" action

Characteristics

• Can produce 1.5-2× more force than concentric

• Lower metabolic cost per unit force

• Greater mechanical efficiency

• Higher risk of muscle damage (DOMS)

• Fewer motor units needed for same force

Examples

• Lowering weight (biceps during curl descent)

• Landing from jump (quadriceps absorbing impact)

• Downhill running (quadriceps controlling descent)

• Decelerating a limb

Importance in Sport

• Essential for deceleration

• Injury prevention (controlled landing)

• Stretch-shortening cycle enhancement

• Training eccentric strength reduces injury risk

6.4 Isometric Contraction

Mechanics

• Muscle force = external resistance

• Cross-bridges cycle but net length unchanged

• Internal movement may occur (tendon stretch)

Types

• Yielding isometric: Holding against gravity/external force

• Overcoming isometric: Pushing against immovable object

Applications

• Postural muscles (constant low-level contraction)

• Rehabilitation (early phase when movement painful)

• Specific angle strength training

• Core stabilisation

Limitations

• Strength gains specific to joint angle trained (±15°)

• Blood flow restricted during contraction

• Blood pressure rises (Valsalva effect)

6.5 Isokinetic Contraction

Definition: Contraction at constant angular velocity throughout range of motion

Requirements

• Special equipment that adjusts resistance

• Accommodating resistance matches force output at every angle

Advantages

• Maximum loading throughout ROM

• Safe — machine controls velocity

• Allows testing and comparison

Applications

• Rehabilitation assessment

• Research (standardised testing)

• Strength profiling (peak torque, angle of peak torque)

7. Motor Unit Physiology

7.1 Motor Unit Definition and Components

Motor Unit: A single motor neuron and all the muscle fibres it innervates

Components

• Motor neuron cell body (in spinal cord anterior horn)

• Axon (travels in peripheral nerve)

• Axon terminals (neuromuscular junctions)

• Muscle fibres (variable number)

Innervation Ratio: Number of muscle fibres per motor neuron

• Fine control muscles: Low ratio (e.g., eye muscles ~5:1)

• Gross movement muscles: High ratio (e.g., gastrocnemius ~2000:1)

7.2 Motor Unit Types

Size Principle

• Motor units recruited in order of size (S → FR → FF)

• Smaller motor neurons have lower activation threshold

• Provides smooth force gradation

• Orderly recruitment ensures efficiency

7.3 Motor Unit Recruitment

Recruitment: Activation of additional motor units to increase force

Process

• Low force: Only S motor units active

• Moderate force: S + FR motor units

• High force: S + FR + FF motor units

Factors Affecting Recruitment

• Force requirements

• Movement velocity

• Fatigue state

• Training status

Recruitment in Different Activities

7.4 Rate Coding

Definition: Modulation of motor unit firing frequency to vary force

Mechanism

• Higher firing rate → greater force per motor unit

• Increased Ca²⁺ release → more cross-bridges

• Summation of twitches → higher tension

Firing Rates

• Minimum: ~5-8 Hz

• Maximum: ~25-50 Hz (varies by fibre type)

• Type I: lower maximum rate

• Type II: higher maximum rate

Tetanus

• Low frequency: individual twitches visible (unfused tetanus)

• High frequency: smooth, sustained contraction (fused tetanus)

• Fusion frequency: rate needed for fused tetanus (~30-50 Hz)

7.5 All-or-Nothing Principle

Principle: When a motor neuron fires, ALL fibres in that motor unit contract maximally (for that stimulus)

Implications

• Individual fibre either contracts fully or not at all

• Force variation achieved by:

  • Recruiting more motor units (spatial summation)

  • Increasing firing rate (temporal summation)

• Not by grading individual fibre contraction

Caveats

• "Maximal" depends on conditions (fatigue, length, velocity)

• Whole muscle force is graded through recruitment and rate coding

7.6 Training Adaptations in Motor Units

Neural Adaptations (Early Strength Gains)

• Increased motor unit recruitment

• Improved rate coding (higher firing frequencies)

• Better synchronisation

• Reduced co-contraction (antagonist inhibition)

• Improved intermuscular coordination

Timeline

• Neural adaptations dominate first 4-8 weeks

• Hypertrophy becomes dominant after 8-12 weeks

• Explains rapid early strength gains without size increase

8. Neuromuscular Junction

8.1 Structure

Presynaptic (Motor Neuron) Side

• Axon terminal (synaptic bouton)

• Synaptic vesicles containing acetylcholine (~10,000/terminal)

• Mitochondria (ATP for vesicle recycling)

• Voltage-gated Ca²⁺ channels

• Active zones (release sites)

Synaptic Cleft

• ~50 nm gap

• Basal lamina containing acetylcholinesterase (AChE)

• AChE rapidly breaks down ACh

Postsynaptic (Muscle) Side

• Motor end plate (specialised sarcolemma)

• Junctional folds (increase surface area)

• Nicotinic ACh receptors (ligand-gated Na⁺/K⁺ channels)

• High receptor density (~10,000/μm²)

8.2 Neuromuscular Transmission

Step-by-Step Process

1. Action potential arrives at axon terminal

   • Depolarisation of terminal membrane

2. Voltage-gated Ca²⁺ channels open

   • Ca²⁺ influx into terminal

3. Ca²⁺ triggers vesicle fusion

   • SNARE proteins mediate fusion

   • Vesicles fuse with presynaptic membrane

4. ACh released (exocytosis)

   • ~200-300 vesicles per AP

   • ~10,000 ACh molecules per vesicle

   • Quantal release

5. ACh crosses synaptic cleft

   • Diffusion (~0.5 ms)

6. ACh binds to nicotinic receptors

   • 2 ACh molecules per receptor

   • Receptor channel opens

7. End-plate potential (EPP) generated

   • Na⁺ in, K⁺ out (net depolarisation)

   • EPP is always suprathreshold (safety factor)

8. Action potential initiated on sarcolemma

   • Voltage-gated Na⁺ channels activated

   • AP propagates along muscle fibre

9. ACh degraded by AChE

   • Hydrolysed to acetate + choline

   • Choline recycled into terminal

10. Vesicles recycled

    • Endocytosis

    • Refilled with ACh

8.3 Characteristics

Safety Factor

• EPP is 3-4× larger than needed to reach threshold

• Ensures reliable transmission

• Fatigue-resistant at low frequencies

One-to-One Relationship

• Every motor neuron AP → muscle fibre AP

• No temporal or spatial summation needed

• Different from CNS synapses

Speed

• Transmission delay ~0.5-1 ms

• Rapid enough for fine motor control

8.4 Clinical Relevance

Myasthenia Gravis

• Autoimmune attack on ACh receptors

• Fewer functional receptors → EPP below threshold

• Muscle weakness and fatigue

• Treatment: AChE inhibitors, immunosuppression

Botulinum Toxin (Botox)

• Blocks vesicle fusion (cleaves SNARE proteins)

• Prevents ACh release

• Causes paralysis

• Therapeutic uses: spasticity, dystonia, cosmetic

Organophosphate Poisoning

• Inhibits AChE

• ACh accumulates

• Continuous stimulation → paralysis

• Cholinergic crisis (nerve agents, pesticides)

9. Muscle Architecture and Force Production

9.1 Architectural Parameters

Fibre Length

• Longer fibres = greater shortening distance = greater velocity

• Number of sarcomeres in series

Physiological Cross-Sectional Area (PCSA)

• Sum of cross-sectional area of all fibres

• PCSA = (Muscle mass × cos θ) / (Fibre length × Muscle density)

• Primary determinant of maximum force

Pennation Angle

• Angle of fibres relative to line of pull

• 0° = parallel (fusiform) muscle

• Higher angle = more fibres pack in, but less force transmitted along tendon

9.2 Muscle Architecture Types

9.3 Force Transmission

Direct Pathway

• Cross-bridge force → myofilaments → Z-line → adjacent sarcomeres → myotendinous junction → tendon → bone

Lateral Force Transmission

• Force transmitted through costameres (attachments to sarcolemma)

• Via endomysium, perimysium, epimysium

• May account for >50% of force transmission

• Important for force distribution and injury prevention

9.4 Tendon Properties

Structure

• Dense regular connective tissue

• Type I collagen fibres (86% of dry mass)

• Hierarchical: collagen molecules → fibrils → fibres → fascicles → tendon

• Tenocytes maintain matrix

Mechanical Properties

• Viscoelastic (time-dependent behaviour)

• High tensile strength (~100 MPa)

• Stiffness increases with loading rate

• Slight elongation stores elastic energy

Stress-Strain Curve

1. Toe region (0-2% strain) — crimped fibres straighten

2. Linear region (2-4%) — fibres stretch; elastic

3. Yield point (~4%) — microdamage begins

4. Failure (8-10%) — complete rupture

Training Adaptations

• Increased stiffness

• Increased cross-sectional area

• Enhanced force transmission

• Takes longer to adapt than muscle (slower turnover)

10. Muscle Adaptations to Training

10.1 Neural Adaptations

Time Course: Dominant in first 4-8 weeks

Adaptations

• Increased motor unit recruitment

• Higher maximal firing rates

• Improved motor unit synchronisation

• Reduced antagonist co-activation

• Enhanced agonist-antagonist coordination

• Improved intermuscular coordination

• Cortical and spinal adaptations

Evidence

• Strength increases without hypertrophy

• Cross-education effect (untrained limb gains strength)

• Rapid initial strength gains

10.2 Muscular Adaptations

Hypertrophy (Increase in Muscle Size)

Myofibrillar Hypertrophy

• Increase in contractile proteins (actin, myosin)

• Addition of sarcomeres in parallel

• Increases force production capacity

• Primary adaptation to resistance training

Sarcoplasmic Hypertrophy

• Increase in sarcoplasm volume

• More glycogen, water, metabolic enzymes

• May contribute to size without proportional strength gain

• More associated with higher-rep, metabolic-stress training

Hyperplasia (Increase in Fibre Number)

• Controversial in humans

• Evidence in animals with extreme overload

• If occurs, likely minor contribution (<5%)

• Satellite cell involvement

Satellite Cell Activation

• Damage or mechanical stress activates satellite cells

• Proliferate and fuse with existing fibres

• Donate nuclei → increased protein synthesis capacity

• Essential for significant hypertrophy

10.3 Resistance Training Adaptations

10.4 Endurance Training Adaptations

Mitochondrial Biogenesis

• Increased mitochondrial volume (up to 100%)

• More oxidative enzymes (citrate synthase, SDH)

• Enhanced fat oxidation capacity

• PGC-1α as master regulator

Capillary Density

• Increased capillaries per fibre

• Improved O₂ and nutrient delivery

• Enhanced metabolite removal

Myoglobin Content

• Increased O₂ storage and diffusion

Fibre Type Transition

• Type IIx → Type IIa (more oxidative)

• Increased Type IIa oxidative capacity

• Minimal Type II → Type I conversion

Substrate Storage

• Increased intramuscular triglycerides

• Increased glycogen storage capacity

11. Factors Affecting Muscle Performance

11.1 Internal Factors

Muscle Size

• Larger PCSA = greater force capacity

• Direct relationship (force ∝ PCSA)

Fibre Type

• More Type II = greater power, velocity

• More Type I = greater endurance

Muscle Length

• Optimal length-tension relationship

• Joint angle affects output

Contraction Velocity

• Force-velocity relationship

• Power optimised at intermediate velocities

Fatigue State

• Metabolic and neural factors

• Reduced force and velocity

Temperature

• Warm muscles contract faster

• Warm-up importance

11.2 External Factors

Load

• Determines contraction type and velocity

• Force adapts to meet resistance (up to maximum)

Joint Angle

• Affects moment arm of muscle

• Affects muscle length

Leverage

• Mechanical advantage of lever system

• Most joints sacrifice force for speed (3rd class levers)

11.3 Training Status

Training Adaptations

• Increased strength, power, endurance

• Improved efficiency

• Enhanced motor control

Detraining

• Neural adaptations lost in 2-4 weeks

• Muscular adaptations persist longer

• Fibre type reverts (IIa → IIx)

11.4 Age-Related Changes

Sarcopenia (Age-related muscle loss)

• Begins ~30 years; accelerates after 60

• ~1-2% muscle mass lost per year after 50

• Preferential Type II fibre loss

• Motor unit remodelling (denervation-reinnervation)

• Reduced satellite cell activity

• Decreased hormone levels (GH, testosterone, IGF-1)

Mitigation

• Resistance training highly effective at any age

• Adequate protein intake (1.0-1.2 g/kg/day for elderly)

• Physical activity maintenance

11.5 Sex Differences

Absolute Differences

• Males ~30-40% more muscle mass

• Higher testosterone → greater hypertrophy potential

• Larger muscle fibres (both Type I and II)

Relative Differences

• Similar force per unit CSA (~25-30 N/cm²)

• Similar fibre type distribution

• Similar relative training adaptations (% improvement)

Training Considerations

• Females can train similarly to males

• Females have faster recovery between sets (lower absolute loads)

• Menstrual cycle may affect performance (variable)

12. Muscle Disorders and Injuries

12.1 Muscle Strains

Definition: Tearing of muscle fibres or tendon

Grading

Common Sites

• Hamstrings (proximal)

• Quadriceps (rectus femoris)

• Gastrocnemius (medial head)

• Adductors (groin)

• Biceps brachii (long head)

Risk Factors

• Previous injury (strongest predictor)

• Inadequate warm-up

• Muscle fatigue

• Muscle imbalances

• Inflexibility

• Age

12.2 Delayed Onset Muscle Soreness (DOMS)

Characteristics

• Pain and stiffness 24-72 hours post-exercise

• Peaks at 48-72 hours

• Resolves within 5-7 days

Cause

• Eccentric exercise primary trigger

• Microtrauma to muscle fibres (Z-line disruption)

• Inflammatory response

• NOT lactic acid (cleared within hour)

Symptoms

• Tenderness to palpation

• Stiffness

• Reduced ROM

• Temporary strength loss

• Swelling

Management

• Light activity promotes recovery

• Massage may help

• NSAIDs controversial (may impair adaptation)

• Repeated bout effect — adaptation reduces DOMS

12.3 Muscle Cramps

Types

• Exercise-associated muscle cramps (EAMC)

• Nocturnal cramps

• Rest cramps

Proposed Mechanisms

• Altered neuromuscular control (most supported)

• Fatigue-induced disruption of alpha motor neuron firing

• Electrolyte imbalance (traditional theory; less supported)

• Dehydration (limited evidence)

Management

• Stretch affected muscle (reciprocal inhibition)

• Adequate conditioning

• Avoid fatigue

• Adequate nutrition and hydration

12.4 Muscular Dystrophies

Duchenne Muscular Dystrophy (DMD)

• X-linked recessive

• Dystrophin gene mutation

• No functional dystrophin → membrane instability

• Progressive muscle weakness

• Wheelchair by ~12 years

• Death by 20s-30s (respiratory/cardiac failure)

Becker Muscular Dystrophy (BMD)

• Also dystrophin mutation (less severe)

• Some functional dystrophin

• Later onset, slower progression

• Life expectancy near normal

13. Summary Tables

Key Muscle Action Roles

Cross-Bridge Cycle Summary

Fibre Type Quick Reference