Module 4

Skeletal Muscles

Under voluntary control

Structure: Muscle

Entire muscle length
Contain fibres

Structure: Muscle Fibres

Parallel
Surrounded by connective tissue
Multinucleated
Many mitochondria

Structure: Myofibrils

Contractile element
Striated: light and dark bands
Organize cytoskeleton into thick and thin filaments

Myofibril: A Band

Dark bands
Stacked thin and thin filaments in parallel
Entire thick filament

Myofibril: I Band

Light bands
Thin filament not in A band

Myofibril: H Zone

Lighter middle of A band
Proteins hold thick filaments together

Myofibril: M Line

H zone midline
Hold myosin heavy chains together

Myofibril: Z Line

I band midline
Sarcomere ends

Sarcomere

Skeletal muscle functional unit
Muscle growth add to sarcomere ends

Cross-Bridges

Connection between myosin heads and actin molecules
A band: Thick and thin filament overlap
Thin filament binding
Thick filament extension

Thick Filament: Myosin

Motor protein: Use ATP to move along actin
2 subunit dimer: Long shaft and globular head
Dimer tails stack with other myosin
Head contain acting and myosin ATPase binding sites

Thin Filament: Actin

Spherical
2 filaments form double helix

Thin Filament: Tropomyosin

Thin double helix
Around actin helix
Regulatory: Cover active binding sites to prevent actin-myosin interaction

Thin Filament: Troponin

3 polypeptides
Bind tropomyosin, actin, Ca2+
Regulatory

Muscle Contraction

Activate tension-generating sites to shorten muscle

Sliding Filament Mechanism

Thin filaments overlap thick filaments
Bring Z lines closer
Shorten sarcomere

Concentric Contraction

Whole muscle shortens

Power Stroke

Interaction between myosin and actin

Power Stroke 1

Myosin cross-bridge binds actin
6 actin around 1 myosin
Cross-bridges pull actin, hold actin position, prepare for power stroke

Power Stroke 2

Myosin head pulls actin inwards
Closer to myosin centre

Power Stroke 3

Cross-bridge detaches
Return original conformation

Power Stroke 4

Cross-bridge binds distal actin
Repeat cycle

Excitation-Contraction Coupling

Convert electrical signal into contraction

T-Tubules

Transverse tubules
Plasma membrane invagination
Between A and I band junction
Perpendicular to fibres

Sarcoplasmic Reticulum (SR)

Membranous
ER in non-muscle cells
Parallel to fibres
Lateral sacs close to T-tubules at fibre end
Store Ca2+

Membrane Depolarization

Electrical signal transmit from T-tubules to SR

Membrane Depolarization 1

Dihydropyridine receptors on T-tubules sense depolarization wave

Membrane Depolarization 2

Ryanodine receptors on SR
Ca2+ channels
Influence by dihydropyridine receptors change conformation

Membrane Depolarization 3

Activate and open ryanodine receptors
Ca2+ enters cytoplasm from SR
Trigger contraction

Ca2+ in Relaxed Muscle

Tropomyosin and troponin prevent cross-bridge formation
Block myosin binding sites on actin

Ca2+ in Excited Muscle

Ca2+ binds troponin
Conformation change
Tropomyosin moves to expose myosin binding sites on actin

Muscle Relaxation

Decrease neuromuscular junction activity to stop acetylcholine release
Stop action potential generation
Acetylcholinesterase removes acetylcholine

Muscle Relaxation 1

SR stop releasing Ca2+

Muscle Relaxation 2

Ca2+ ATPase pump Ca2+ from cytosol into SR

Muscle Relaxation 3

Troponin and tropomyosin covers actin

Cross-Bridge Cycling 1

Myosin head ATPase site binds ATP
Form ADP and Pi
Stored energy transfer to myosin cross-bridge (Ready to fire)

Cross-Bridge Cycling 2

Ca2+ present
Troponin-tropomyosin complex exposes actin
Cross-bridge binds actin and swings
Power stroke (fire)

Cross-Bridge Cycling 3

Release Pi and ADP to empty ATPase site
Cross-bridge bound to actin

Cross-Bridge Cycling 4

New ATP binding
Cross-bridge detach
Return conformation

Cross-Bridge Cycling 5

Ca2+ absent
No contraction (ready to fire)

Cross-Bridge Cycling 6

Rigor mortis after death
Increase Ca2+
Muscles stay contracted
Cross-bridges attached (Ready to fire)
Protein decay and relaxation after days

Muscle Twitch

Minimal muscle contraction from single action potential
Increase with tension
Temporal relationship

Muscle Twitch: Latent Period

Short action potential from 1 muscle (1-2 msec)
Delay before contraction
Complete previous action potential
Cross-bridge cycling begins

Muscle Twitch: Contraction Time

Actin sliding
Peak tension (40-120 msec)
Vary from muscle type and location

Muscle Twitch: Relaxation Time

Contraction continues until no Ca2+ (20-200 msec from peak)

Motor Unit Recruitment

Motor neuron innervate non-adjacent muscle fibres (Motor unit)
Nerve activation contracts entire motor unit in rotation
Prevent fatigue and increase tension

Optimal Length

Muscle length generating tension for max force

Less Than Optimal

Shortened fibre
Thin filament overlap thick filaments without cross-bridges (thick filaments touch Z lines)
Sarcomeres overlap
Decrease contraction efficiency and tension
70% of optimal

Optimal

Max cross-bridge binding sites available
Thin filaments do not overlap central thick filament region
No cross-bridges
Muscle at rest

Greater Than Optimal

Passive stretch
Less thick and thin filament overlap
Increase Z-line distance
Less tension and no contraction
70% longer than optimal

Joint

Muscles attached to 2 bones
Connective tissue tendon around muscles

Joint: Elbow

Contract biceps to bend
Contract triceps to straighten

Muscle Tension with Load

Muscle contracts and exceeds force opposing movement
Greater force and load = difficult tension and contraction

Myalgia

Muscle soreness
From overexertion and improper rest

Muscle Injury: Contusion

Compressive force

Muscle Injury: Strain

Force from intrinsic tension
Mild: Delayed muscle soreness
Severe: Rupture muscle fibre and connective tissues

Muscle Injury: Laceration

Deep muscle cut

Muscle Injury: In Situ Necrosis

Partial necrotized muscle

Stimulation Frequency

Quick membrane repolarization
Undergo many short action potentials

Restimulation After Complete Relaxation

Second twitch same magnitude as first

Restimulation Before Complete Relaxation

Second twitch added to first
Twitch summation

Fast Stimulation

Twitches overlap
Tetanic contraction

Fast Stimulation: Unfused

No complete relaxation between stimuli

Fast Stimulation: Fused

No relaxation between stimuli
Strongest twitch
Tetanus

Motor Unit: Isotonic Contraction

Constant tension
Change length
Movement with no muscle tension increase

Motor Unit: Isometric Contraction

Increase tension
Constant length
Static contraction
No movement with muscle tension increase

Whole Muscle Contractions

Types of isotonic contractions

Whole Muscle: Concentric Dynamic Contractions

Increase tension
Decrease length
Ex: Lifting with biceps

Whole Muscle: Eccentric Dynamic Contractions

Increase tension
Increase length
Ex: Lowering with biceps

Fatigue

Muscles cannot maintain contraction and tension decreases

Central Fatigue

CNS decrease motor neuron activity
Muscle fibres not fatigued
Boredom, tired, lack motivation

Muscle Fatigue

Muscle cell protection
Reduce activity before ATP runs out

Muscle Fatigue Causes: ADP and Pi Accumulation

From ATP hydrolysis
Interfere with cross-bridge cycling

Muscle Fatigue Causes: Lactic Acid Accumulation

Inhibit glycolysis
Reduce ATP production
Interfere with excitation-contraction coupling

Muscle Fatigue Causes: Extracellular K+ Accumulation

No Na-K pump function
Na+ and K+ gradients not restored
Membrane depolarizes
Less excitable muscle fibres

Muscle Fatigue Causes: Glycogen Depletion

Extreme exercise

Slow Twitch Fibres

Type 1
Slower contraction
A2 motor neurons
Smaller
Lower activation threshold and conduction
Slow ATPase and cross-bridge cycling
Resist fatigue
Lower force production
Slow Oxidative: Aerobic ATP production

Fast Twitch Fibres

Type 2
A1 motor neurons
Larger
Higher activation threshold and conduction
Fast ATPase and cross-bridge cycling
Fatigable
Higher force production
Fast Oxidative Glycolytic: Aerobic and anaerobic ATP production
Fast Glycolytic: Anaerobic ATP production

Muscle Colour

Energy production method

Red Fibres

Slow oxidative and fast oxidative glycolytic
Aerobic metabolism
Many mitochondria
Highly vascularized
Myoglobin support O2 use (red)

White Fibres

Fast glycolytic fibres
Anaerobic metabolism
Few mitochondria
No myoglobin (pale)

Muscle Receptors

Mediate CNS input and proprioception

Muscle Receptors: Muscle Spindles

Monitor muscle length changes and stretch reflex
Transmit to CNS
Sensory afferent fibres in muscle spindle centre

Muscle Spindles: Intrafusal Fibres

Specialized muscle cell collection
Connective tissue in extrafusal fibres
Contractile end
Innervated by gamma motor neurons

Muscle Spindles: Extrafusal Fibres

Muscle fibres
Innervated by alpha motor neurons

Muscle Receptors: Golgi Tendon Organs

Monitor muscle tension changes
In tendon and muscle junctions
Extrafusal fibre contraction activate afferent fibres
Brain reads info subconsciously (length) and consciously (tension)

Afferent Neuron Input

Spinal cord and reflexes
Maintain posture and protective movements

Primary Motor Cortex Input

Descending fibres from pyramidal cells
Terminate on motor neurons in spinal cord

Primary Motor Cortex: Corticospinal Motor System

Fine voluntary movement

Brainstem Input

Regulate posture and large involuntary movement

Brainstem: Multineuronal Motor System

Influenced by cortex, cerebellum, basal nuclei

Brainstem Nuclei Damage

Decrease motor neuron input and muscle excitation
Hinder voluntary movement

Muscle Spindle Damage

Damage peripheral receptor
Affect muscle length detection
Hinder afferent nerve transmission to brainstem and primary cortex
Hinder voluntary movement coordination

Smooth Muscle Structure

Spindle diamond pattern from filaments
1 nucleus
Smaller length and diameter
Muscle sheets
No sarcomeres and T-tubules
Dense bodies on internal plasma membrane anchor intermediate and contractile filaments

Smooth Muscle: Myosin

Thick and long

Smooth Muscle: Actin

Thin
Tropomyosin only

Smooth Muscle: Intermediate Filaments

Direct contraction and cytoskeleton support

Smooth Muscle: Length-Tension

Below optimal tension at rest
Stronger contraction when stretched
Greater stretch and contraction for forceful emptying

Myosin Light Chain

Protein on myosin head
Help cross-bridge formation in smooth muscle