Neuromuscular Unit

Fast interactions with the environment: objective of neurons.

Large effective unit: response to motor command from our brain → action

Ventral Horn (Anterior Horn/Anterior Horn Cell) of Spinal cord: houses thousand of motor neurons

motor neuron (in ventral horn) → axon → branching → NMJ → Effector Muscle

Q: How many muscle fibers can one neuron command?

Branches in axon terminals:

  • limitation due to electrical properties and arrangement of Na+ → limit branch

  • Reliability on one single neuron is not effective.

  • Small Motor Units:

  • Large Motor Units: up to 1000 fibers

Motor Unit

  • smallest functional unit of neuromuscular unit

  • single motor neuron → projects axon with branches → innervate multiple muscle fibers within the same muscle

  • Each muscle fiber is innervated by a single motor neuron

  • Fine Motor Muscles: smaller motor unit (ex. hand, fewer number of innervated muscle fibers

  • Coarse Motor Muscles: larger motor unit (ex. thigh)

  • Why?: we need many computational units to control fine movement.

Anterior Horn Cells

  • Ventral root merge with dorsal root → Spinal Nerve?

  • One root supply many muscles

  • One muscle supplied by many roots

Peripheral Nerve

  • smallest circle = single neuron

  • Grouped together: Fascicle

  • Large Peripheral nerve: many fascicles

  • Layers:

    • Endoneurium: loose connective tissue that lies between each neuron in the fascicle.

    • Perineurium: dense type of connective tissue that covers each fascicle

    • Epineurium: loose connective tissue that covers the peripheral nerve (outermost)

    • Vasa nervorum

  • Types of Peripheral Nerve: classified by Axon size correlates with function (see slide 10,11)

    • A alpha: large diameter with myelin.

    • A beta: large but secondary to A alpha: sensory axons that receive many sensory stimulus: touch, pressure, vibration, proprioception but not pain prick and temp.

    • C: very small and unmyelinated.

    • Responsible for autonomic neurons

    • Axon that serves pain prick and temperature : C fiber

    • Differe nt types of axons have different velocities: up to 100 m/s (large), small velocity around 3 - 10 m/s.

    • Gamma motor neuron: controls muscle tone Passive resting small contractions within muscles (slight contract)

  •    Alpha vs. Gamma Motor Neuron

    • Alpha

      • Type 1: slow twitch, Type 2: fast twitch

      • Type 2 larger > 1 because requires more force exertion in a single movement

  • How many synapse in a muscle fiber? Only One

Physiology and Electrophysiology of NMJ: see slide 16 → 19 (SOS)

(18.) Quanta = molecules

EPP = End Plate Potential is caused by Acetylcholine bind with receptor → Na+ influx into cell → Grated Potential: depends on amount of Sodium influx through acetykcholine receptors (not all or none like action potential), if a threshold is reached → action potential in muscle membrane is induced.

Why does muscle membrane require action potential? Action potential can send long signals without decrease → send signal deeply into T-tubule in muscular cell: activate fibers → muscle contraction

End plate potential: although reduced, is still higher than the threshold that generates action potential → continuous action potential generation

5 molecules of acetylcholine → produce 1 mV of EPP

15 mV of EPP is the threshold required to → Action Potential

Myasthenia Gravis

Lambert-Eaton Mysathenic Syndrome

  • Acetylcholine in synaptic cleft reduced from 200 to 20 from the very beginning.

T-Tubule:

  • tube invaginate down to sarcoplasmic reticulum: special organelles in muscle that stores Calcium, sarcolemma. → activates Calcium release in Sarcoplasmic reticulum (elaborate more on the process) something about DHPR → Ryanodine Receptor RYR → ???

  • Excitation Contraction Coupling

    • Cross-bridge formation: calcium binds to troponin C → change in troponin-tropomyosin conformation → tropomyosin moves → cleft, leaves binding sites exposed → myosin attaches head to exposed binding site.

    • Sliding FIlament Theory: Myosin head touch with actin → Pi is removed → Pwer stroke: Actin gets pulled towards middle of sarcomere → ADP released → New ATP binds to myosin head → unbinding of myosin and actin → cocking of myosin head → start over

    • Relaxation: reduction of calcium (calcium reflux back into sarcoplasmic reticulum depends on concrentration of Calcium ion) → troponin can not stroke acti anymore even with ATP NOT related to ATP depletion.

    • What happens if ATP is depleted but not Calcium? → Cramping (excessive use of muscle): ATP completely depleted → can NOT unbind myosin head out of actin → contraction.

What defines force of contraction?

  1. Temporal Summation: “Tetany”: every single motor unit can gradually increase the force by itself.

  2. Spatial Summation: “Recruitment”

Neuromuscular Unit Pathology

Differentiate between upper and lower motor neuron lesions:

  • Upper: primary motor cortex: pyramidal

  • Whys does cell body lesion → Atrophy? Muscles require neurotrophic factor produced by cell body from neurons for muscle to survive, Once muscle lacks these factors → slowly die off.

  • Atrophy & Fasciculations can be used to differentiate

Symptoms and Manifestations of NMJ Disorders:

Pre-synaptic disorders:

Lambert-eaton syndrome (LEMS)

• Persistent chronic progressive weakness with significant improvement on brief exercise        

• Affect proximal muscles (esp. lower exrtemities) with early sparing oculo-bulbar muscles    

• Hyporeflexia (improved with exercise), hypotonia

• Autonomic dysfunction as well

Botulism

  • Acute weakness from the intoxication (12-36 hours)

  • Affect all muscles from oculobulbar to respiratory muscles (if severe, leading to death)

  • Autonomic dysfunction

Post-synaptic disorders

Myasthenia Gravis

  • Progressive intermittent weakness with ‘fatigability’/’fluctuated’ pattern (diurnal variation : strong in the morning, weaker in the afternoon)

  • Affect the oculo-bulbar muscles and proximal muscles.

  • Normal reflex

  • Only Weakness

Clinical Correlations: see case discussion