Comprehensive Notes on Muscle Anatomy, Physiology, and Eye Movements

Spatial and Temporal Summation

• Spatial Summation:

  • Process: Light is combined by receptive fields over the stimulus area.
  • Governed by: Ricco’s law of complete spatial summation and Piper’s law of incomplete summation.

• Temporal Summation:

  • Process: Light is combined by receptive fields over the stimulus duration.
  • Governed by: Bloch’s law.

Vision Loss and Receptive Fields

• Vision Loss: Sensitivity/vision loss in glaucoma and age-related macular degeneration are associated with changes in receptive fields within the visual pathway.

• Functional Biomarkers for Glaucoma: Changes in Ricco’s area (spatial summation) and critical duration (temporal summation) serve as primary functional biomarkers.

• Location of Changes: The exact location of these changes within the visual pathway remains a subject of ongoing research.

Visual Pathway and Lesion Localization

• Importance of Visual Pathway Knowledge: Understanding the visual pathway and patterns of visual field defects aids clinicians in tentatively locating lesions.
  • Example: Visual field defect resembling no. 3 might suggest a compressive lesion at the optic chiasm.

Recommended Reading

• Schwartz (1999). Visual Perception. A Clinical Orientation. Chapters 2, 12, 13, 14 & 15.

• Livingstone and Hubel. “Segregation of Form, Color, Movement, and Depth: Anatomy, Physiology, and Perception” (PDF on Blackboard).

• Useful website: http://www.webvision.med.utah.edu/

Muscle Tissue

• Major Cell Types:

  • Skeletal muscle
  • Smooth muscle
  • Cardiac muscle

• Each muscle consists of bundles of muscle cells (myofibres or muscle fibres) embedded in a matrix of connective tissue (fascia).

• Properties of Muscle Tissue:

  • Excitability: Responds to stimuli (from neurons).
  • Contractibility: Able to shorten in length and thicken in diameter.
  • Extensibility: Stretches when pulled beyond normal length.
  • Elasticity: Tends to return to original shape & length after contraction or extension.

Skeletal Muscle

• Comprises approximately 40% of the mass of the average human body.

• Usually contracts voluntarily.

• Can produce short, single contractions (twitch) or long, sustained contractions (tetanus).

• Function: Maintenance of posture, motion, and heat production.

Skeletal Muscle Structure

• Attached to bones via tendons, facilitating skeletal movement.

• Divided into bundles of fibres (fascicles) that run parallel to one another.

• Each fascicle is composed of a bundle of myofibres (=muscle fibres, muscle cells).

• Myofibres appear striated (striped) under electron microscopy.

Skeletal Muscle: Striations in Myofibres and Myofibrils

• Key structural components:
  • Sarcolemma
  • Myofibrils
  • Terminal cisternae
  • Transverse tubule
  • A band
  • Sarcoplasmic reticulum
  • Mitochondria
  • I band
  • Z line
  • Z disc
  • Nucleus

Hierarchical Organization of Skeletal Muscle

• Muscle as an Organ:

  • Each muscle is surrounded by fibrous connective tissue (epimysium).
  • Contains blood vessels and nerves.
  • Composed of several fascicles (bundles).

• Fascicle:

  • Bundle of muscle cells (myofibres).
  • Surrounded by fibrous connective tissues (perimysium).
  • Contains blood vessels and nerve fibres.

• Myofibre (Muscle Cell):

  • Long cylinders (often several cm long, from tendon to tendon; 10 to 100 $μm$ in diameter).
  • Specialized for contraction.
  • Surrounded by fibrous connective tissues (endomysium).
  • Has blood vessels and nerve fibres.
  • Contains a group of myofibrils.

• Myofibril:

  • Organelle (1-2 $μm$ in cross-section).
  • 1000-2000 myofibrils per myofibre.
  • Contains myofilaments arranged in a series of sarcomeres.

Myofibre Details

• Myofibre = Muscle Cell:
  • Contains usual cell organelles.
  • Sarcolemma: Cell membrane of skeletal muscle cell.
    • Extends deep into the cell as transverse tubules, increasing cell membrane surface area and proximity to terminal cisterns of the sarcoplasmic reticulum.
  • Sarcoplasmic reticulum
  • Mitochondria
  • Multiple nuclei
  • Sarcoplasm + Myofibrils
  • Z disc

Motor Units

• Extraocular muscles (eye movement): 10-20 myofibres per motor unit.

• Biceps brachii (arm) or gastrocnemius (calf): 2000-3000 myofibres per motor unit.

Muscle Contraction Process

• Simultaneous contraction of myofibrils leads to myofibre contraction.

• Neural Excitation at Neuromuscular Junctions:

  1. Acetylcholine binds to its receptors, opening them as $Na^+$ channels.
  2. Influx of $Na^+$ leads to local depolarization of the sarcolemma and generation of a muscle action potential.
  3. Depolarization spreads via T tubules.
  4. Opening of voltage-gated $Ca^{2+}$ channels in the sarcoplasmic reticulum (SR).
  5. Massive, rapid movement of $Ca^{2+}$ from SR into the sarcoplasm.

Myofilaments

• Myofibrils contain two types of filaments along their long axis:
  • Thin filament: mainly actin.
  • Thick filament: myosin.
• Each thick filament is surrounded by six thin filaments.

Sarcomere

• A single myofibril is composed of many short structural units, known as sarcomeres, which are arranged end to end.

• The proteins at the junctions between sarcomeres form the Z line (Z disk).

• Represents the minimal contractile unit of a muscle.

Sliding Filament Model

• Muscle contraction is achieved through the sliding filament model.

• Coordinated contraction of millions of sarcomeres within a muscle leads to overall muscle contraction.

Thin and Thick Filaments

• Thin Filament:

  • Composed primarily of actin, along with accessory proteins tropomyosin and troponin.
  • G-actin monomers polymerize into long fibrous arrays (F-actin).
  • Two linear F-actin arrays are helically woven around each other to form the backbone of one complete thin filament.
  • Tropomyosin wraps around the actin filament.
  • Troponin is present at the end of each tropomyosin molecule.

• Thick Filament:

  • Composed of myosin molecules.

Thin Filament Regulation by Calcium

• In the absence of $Ca^{2+}$, tropomyosin blocks cross-bridge binding sites on actin.

• When $Ca^{2+}$ is present:

  • $Ca^{2+}$ binds to troponin.
  • This binding causes the troponin-tropomyosin complex to shift, exposing the cross-bridge binding sites on actin.

Myosin and the Thick Filament

• Myosin possesses binding sites for both ATP and actin.

Cross-Bridge Cycle

1. Resting fiber: cross bridge not attached to actin

2. Cross bridge binds to actin

3. Power stroke causes filaments to slide

4. A new ATP binds to myosin head, allowing it to release from actin

5. ATP is hydrolyzed, causing cross bridge to return to its original orientation

Role of Calcium in Muscle Contraction

• Muscle contraction is regulated by the level of $Ca^{2+}$ in the sarcoplasm.

• In skeletal muscle, calcium ions work at the level of actin (actin-regulated contraction).

• $Ca^{2+}$ moves the troponin-tropomyosin complex off the binding sites, allowing actin and myosin to interact.

Role of ATP in Muscle Contraction

• At the end of the power stroke, the actin-myosin complex remains intact until ATP becomes available.

• Upon ATP binding to myosin, the myosin head is displaced from actin.

  • ATP is required for muscle relaxation.

• ATP hydrolysis is needed for the return of the myosin head to its resting conformational state.

• The final product is also the first reactant – the contractile cycle.

Muscle Contraction Visualized

• Relaxed Muscle: I band visible, sarcomere at resting length.

• Contracting Muscle: Sarcomere shortens, I band shortens, H zone shortens.

• Maximally Contracted Muscle: Sarcomere significantly shortened, I band nearly disappears, H zone disappears, A band remains constant.

Muscle Relaxation

• Electrical quiescence at the myoneural junction.

  • Sarcolemma returns to its resting electrical potential (about -60mV), as does the entire transverse tubule system and the SR membrane.

• Removal of sarcoplasmic $Ca^{2+}$ (ATP-driven $Ca^{2+}$ pumps in sarcoplasmic reticulum and mitochondria).

• Cessation of contractile activity and a state of relaxation.

Tetany/Muscle Cramps

• Hypercontracted muscle following prolonged, repetitive stimulation.

• Caused by depletion of ATP:

  • Raised sarcoplasmic $Ca^{2+}$ because no ATP is available to re-sequester $Ca^{2+}$ into the cisternae of the sarcoplasmic reticulum, so $Ca^{2+}$ remains bound to troponin.
  • Highly contracted muscle because no ATP is available to break actomyosin crossbridges.

Sources of ATP in the Muscle

• Creatine phosphate (enough for up to 15s).

• Anaerobic glycolysis from breakdown of glucose into pyruvic acid; in low O2, pyruvic acid is converted to lactic acid (anaerobic cellular respiration) (enough for up to 30-40s).

• Aerobic cellular respiration based on oxidative phosphorylation in mitochondria where O2, pyruvic acid/fatty acids/amino acids are used as substrates.

Types of Skeletal Myofibres

• Slow Oxidative Fibres (Red):

  • High concentration of myoglobin.
  • Abundant mitochondria.
  • Very resistant to fatigue but not as fast as fast oxidative fibres.

• Fast Oxidative Fibres:

  • Also high concentration of myoglobin and mitochondria.
  • High glycogen stores so can generate ATP by both anaerobic glycolysis and aerobic respiration.

• Fast Glycolytic Fibres (White Fibres):

  • Low concentration of myoglobin and mitochondria.
  • Large amounts of glycogen.
  • Intense movements of short duration.

Rigor Mortis

• The rigid state of muscles that develops shortly after death is due to this highly cross-linked state of thin and thick filaments.

• Loss of energy supplies → ion equilibration → SR and extracellular $Ca^{2+}$ leaking into the sarcoplasm → raise in $Ca^{2+}$ concentrations to high levels → exposure of actin binding sites to myosin → uncontrolled contractile activity hastens the total exhaustion of ATP supplies and ends with all or nearly all myosin molecules in actomyosin crossbridges.

Contraction Models

• Sliding filament model of muscle contraction applicable to smooth, skeletal, cardiac, and other contractile activity, including mechanochemical events such as single-cell locomotion and receptor endocytosis.

Smooth Muscle

• Found in the walls of all the hollow organs of the body (except the heart).

• Contraction reduces the size of these structures.

• The contraction of smooth muscle is usually involuntary (controlled by the autonomic nervous system).

• Examples of its action:

  • Regulates the flow of air through the lungs.
  • Regulates the flow of blood in the arteries.
  • Moves food along through your GI tract.
  • Expels urine from your urinary bladder.
  • Sends babies out into the world from the uterus.
  • Iris sphincter and dilators constrict or dilate the pupil.

Smooth Muscle Structure

• Spindled shape (65-300 $μm$ x 5-10 $μm$).

• Single centrally located nucleus.

• Contractile apparatus (sarcomere-like structure based on actin and myosin).

Smooth Muscle Properties

• Ability to stretch and maintain tension for long periods of time.

• Contracts involuntarily.

• Unique Mechanical Properties:

  • Slow shortening velocity.
  • Slow actomyosin ATPase (i.e., slow crossbridge cycle).
  • High economy of energy utilization during isometric contraction.

Smooth Muscle Comparison

• Comparison of smooth and skeletal muscle contraction:
  • Force: smooth 3x less than skeletal
  • Velocity smooth 100 x less than skeletal
  • Energy Consumption: Smooth 300 x less than skeletal

Cardiac Muscle

• Makes up the wall of the heart.

• Striated.

• Twitch muscle only.

• Involuntarily.

• Contracts ~ 70 times per minute pumping about 5 liters of blood each minute throughout life.

Heart Muscle Properties

• Endurance and consistency: it can stretch in a limited way, like smooth muscle, and contract with the force of a skeletal muscle.

Extraocular Muscles (EOMs)

• Learning outcomes:
  • Describe the origins, insertions and innervation of the EOMs
  • Describe the actions of EOMs in primary and secondary positions
  • Name the different types of ductions, versions and vergences
  • Describe and apply the laws monocular and binocular eye movements
  • Briefly describe the major types of eye movement

WHAT DO YOUR EYE MUSCLES NEED TO BE ABLE TO DO?

• Vergence movements (convergence)
• Version movements (dextroversion)
• Version movements (laevoelevation)
• Version movements (laevocycloversion)

Other Classes of Eye Movements

• Saccades
  • Short, sharp, fast movements
  • Like when you are reading a book
• Smooth pursuit
  • Eye follows a target
  • More accurate at low speeds
• Vestibular- ocular response
  • Compensatory eye movements related to change in head position

Extraocular Muscles

• 6 Extraocular Muscles That Move The Eye
• Plus, the levator palpebrae superioris which elevates the upper eyelid.
  • This will not be considered here

Origin of the EOMs

• Roof of orbit

  • Trochlea
  • Bend of superior oblique by 51°

• Medial surface of the maxilla

  • Inferior oblique

• Apex of Orbit

  • Annulus of Zinn
  • All other EOMs

Insertion of Recti Muscles

• Superior rectus muscle-6.9
• Lateral rectus muscle-
• Inferior oblique muscle-7.7
• Superior oblique tendon
• Medial rectus muscle-6.5
• Inferior rectus muscle-6.5

Insertion of The Oblique Muscles

• Superior oblique
  • Superior lateral surface, posterior to equator
• Inferior oblique
  • Inferior lateral surface, posterior to equator

Position of the Eyeball in the Socket

• Lateral rectus
• Medial rectus
• Superior rectus
• Straight ahead

Monocular Eye Movements

• Centre of rotation

Rotation of the Eyeball

• 3 axes known as Axes of Fick
  • x axis: Vertical rotation (up/down)
  • z axis: Horizontal rotation (left/right)
  • y axis / optical axis: Cyclorotation (twists in/out)
  • Listings plane Equator

Monocular Eye Movements (Ductions)

• Abduction = outwards
• Adduction = inwards Lateral
  • Depression/Deorsumduction = downwards
  • Elevation/Sursumduction = upwards Vertical
• Excycloduction = rotates outwards (from top)
• Incycloduction = rotates inwards (from top) Rotational

Positions of Gaze

• Primary position – eyes straight ahead
• Secondary position – eyes straight up/down/right/left
• Tertiary position – eyes up & right / up & left / down & right / down & left
• In total there are NINE positions of gaze, and we examine them all!
  • RLR LMR
  • RMR LLR
  • RSR LIO
  • RIR LSO
  • RIO LSR
  • RSO LIR

Lateral Rectus

• 6th (abducens) nerve
• Rotates around z (vertical axis)
• In primary position:
  • 1o action: abduction
  • 2o action: none
  • 3o action: none

Medial Rectus

• 3rd (oculomotor) nerve
• Rotates around z (vertical axis)
• In primary position:
  • 1o action: adduction
  • 2o action: none
  • 3o action: none

Superior Rectus

• 3rd (oculomotor) nerve
• Rotates around x-y plane, 67o nasal to y
• In primary position:
  • 1o action: elevation
  • 2o action: incycloduction
  • 3o action: adduction

Inferior Rectus

• 3rd (oculomotor) nerve
• Rotates around x-y plane, 67o nasal to y
• In primary position:
  • 1o action: depression
  • 2o action: excycloduction
  • 3o action: adduction

Superior Oblique

• 4th (trochlear) nerve
• Rotates around x-y plane 39o temporal to y
• In primary position:
  • 1o action: incycloduction
  • 2o action: depression
  • 3o action: abduction

Inferior Oblique

• 3rd (oculomotor) nerve
• Rotates around x-y plane 39o temporal to y
• In primary position:
  • 1o action: excycloduction
  • 2o action: elevation
  • 3o action: abduction

Mnemonic Memory Aids

• “Only inferior muscles sink as low as extorsion”
  • Inferior rectus and inferior oblique extort (excycloduction)
  • Superior rectus and superior oblique intort (incycloduction)
• RADSIN
  • Superior and inferior muscles ONLY!
  • Recti adduct (superior and inferior rectus)
  • Superior intort (superior rectus and superior oblique)

DONNDER’S LAW

• “For a specific oblique (tertiary) position of gaze, there is always a particular amount of torsion present” (Stidwell p136)

• “To each position of the line of sight belongs a definite orientation of the horizontal and vertical retinal meridians relative to the coordinates of space irrespective of the route taken” (Rowe, p 431)

• Doesn’t matter about previous eye position, the ocular orientation required to look at a particular point in space is always the same and independent of previous position

LISTING’S LAW

• “Each movement of the eye from the primary position to any other position involves a rotation around a single axis lying in the equatorial plane called Listing’s plane” (Rowe, p435)

Eye Position and Muscle Actions

• Not all eye muscles are inserted so that they lie along one of the 3 axes of Fick in 1 o position
• In different directions of gaze the actions of the muscles change
• Medial/lateral rectus: small effect
• Superior/inferior muscles: greater effect
  • FOR EXAMPLE: Actions of superior rectus will be different in primary position (blue arrow) to a bduction (green arrow)

Medial and Lateral Recti

• LR and MR muscles align with y axis (of Fick)
  • Not obliquely inserted
  • Hence only lateral movement from primary position
• Even in elevation or depression there is little change in action
  • In elevation, some extra elevation
  • In depression, some extra depression

(R) Superior Rectus – Primary Position

• Muscle inserted at 23o
• Therefore, results in movement across all 3 axes of Fick
• Actions in PRIMARY position
  • Elevation
  • Incycloduction
  • Adduction

Superior Rectus – In Abduction

• Eye rotates outward
• SR aligns with optical (y) axis of the eye – contraction results in elevation
• When the eye is abducted, the SR mainly elevates the eye

(R) Superior Rectus – In Adduction

• Eye rotates inward
• SR nearly perpendicular to optical (y) axis of the eye – contraction results in increased intorsion
• When the eye is adducted, the SR mainly results in incycloduction of the eye. Some elevation.

(L) Inferior Rectus – Primary Position

• Muscle inserted at 23o
• Therefore, results in movement across all 3 axes of Fick
• Actions in PRIMARY position
  • Depression
  • Excycloduction
  • Adduction

(L) Inferior Rectus – In Abduction

• Eye rotates outward
• IR aligns with optical (y) axis of the eye – contraction results in elevation
• When the eye is abducted, the IR mainly depresses the eye

(L) Inferior Rectus – In Adduction

• Eye rotates inward
• IR nearly perpendicular to optical (y) axis of the eye – contraction results in increased intorsion
• When the eye is adducted, the IR mainly results in excycloduction. Some depression.

(R) Superior Oblique – Primary Position

• Muscle inserted at 51o
• Therefore, results in movement across all 3 axes of Fick
• Actions in PRIMARY position
  • Depression
  • Incycloduction
  • Abduction

(R) Superior Oblique – In Abduction

• Eye rotates outward
• SO nearly perpendicular to optical (y) axis of the eye – contraction results in increased intorsion
• When the eye is abducted, the SO mainly results in incycloduction of the eye

(R) Superior Oblique – In Adduction

• Eye rotates inward
• SO nearly aligned with optical (y) axis of the eye – contraction results in increased depression
• When the eye is adducted, the SO mainly depresses the eye

(L) Inferior Oblique – Primary Position

• Muscle inserted at 51o
• Therefore, results in movement across all 3 axes of Fick
• Actions in PRIMARY position
  • Elevation
  • Excycloduction
  • Abduction

(L) Inferior Oblique – In Adduction

• Eye rotates inward
• IO nearly aligned with optical (y) axis of the eye – contraction results in increased elevation
• When the eye is adducted, the IO mainly elevates the eye

(L) Inferior Oblique – In Abduction

• Eye rotates outward
• IO perpendicular to optical (y) axis of the eye – contraction results in increased extorsion
• When the eye is abducted, the IO mainly results in excycloduction of the eye

Binocular Eye Movements

• Vergences (opposite direction, disjunctive) (Convergence):
  • RMR LMR
  • Divergence: RLR LLR
  • Incyclovergence RSO LSO
  • Excyclovergence RIO LIO
  • Right infra(deorsum) vergence RIR
  • Left infra(deorsum) vergence LIR
  • Right supra(sursum) vergence RSR
  • Left supra(sursum) vergence LSR

Versions (same direction, conjugate)

• Dextroversion
• laevoversion : RMR LMR RLR LLR
• Dextrocycloversion RSO LSO
• Laevocycloversion RIO LIO
• Supra(sursum) version RSR LSR
• Infra(deorsum) version LIR RIR

Binocular Interactions

• Looking Right:
  • Right lateral rectus contracts
  • Left medial rectus contracts
  • Right medial rectus relaxes
  • Left lateral rectus relaxes
• Yoke muscles / Synergists / Agonists
• Antagonists
• Ipsilateral = same side e.g. RLR and RMR
• Contralateral = opposite side e.g. RLR and LMR

Sherrington’s Law of Reciprocal Innervation

• Ipsilateral/ direct antagonists
• Pull one eye in opposite directions
• Increased innervation to a muscle is accompanied by a decrease in innervation in the ipsilateral antagonist:
  • RLR contracts, RMR relaxes, etc.

Hering’s Law

• Contralateral agonists / synergists (yoke muscles)
• Move each eye in same direction
• When innervation to a muscle changes, an equal change in innervation occurs in the contralateral synergist:
  • Innervation to right lateral rectus will result in equal innervation to the left medial rectus

Convergence

• Right medial rectus contracts
• Left medial rectus contracts

Positions of Gaze

• Primary position – eyes straight ahead
• Secondary position – eyes straight up/down/right/left
• Tertiary position – eyes up & right / up & left / down & right / down & left
• In total there are NINE positions of gaze, and we examine them all!
  • RLR LMR
  • RMR LLR
  • RSR LIO
  • RIR LSO
  • RIO LSR
  • RSO LIR

Looking Up to the Right

• Left eye adducted.
• Left inferior oblique elevates eye in adduction
• Right eye abducted.
• Right superior rectus elevates the eye in abduction

Looking Down to the Left

• Left eye abducted
• Left inferior rectus depresses eye in abduction
• Right eye Adducted
• Right superior oblique depresses eye in adduction