L17 Motor Units + Neuromuscular Transmission Flashcards Preview

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Flashcards in L17 Motor Units + Neuromuscular Transmission Deck (24):

Learning Outcomes (for general perusal)

  1. Describe the synthesis and storage of acetylcholine
  2. Outline the release mechanism of acetylcholine, with particular emphasis on the role of calcium ions in triggering this
  3. Describe the functional properties of the postsynaptic (muscle) receptor and ion channel, and describe how acetylcholine produces a depolarisation in the muscle fibre
  4. Review the features of the neuromuscular junction which facilitate a very rapid transmission process
  5. Describe the termination of the action of acetylcholine through its hydrolysis by choline esterase
  6. Predict how blockade of the acetylcholine receptor, or of the choline esterase, can disrupt neuromuscular transmission
  7. Appreciate that cell-to-cell communication occurs via chemical mediators, and that acetylcholine at the neuromuscular junction is an example of this


Where are nerve impulses converted to mechanical force?

at the neuromuscular junction (NMJ)


  1. What is the basic unit of motor control?
  2. What is it defined as?
  3. Where do small motor units tend to be?
  4. Where are the larger motor units?

  1. The motor unit
  2. the one motor neurone and all of the muscle fibres it innervates.
  3. muscles requiring fine control (extraocular muscles or finger muslces)
  4. postural muscles that need sustained, prolonged contractions


How is the wide range of degree of muscle control achieved?

 by a heirarchy of control systems

These range from the junction between nerve and muscle itself, through the control exerted through individual motor nerves and the reflexes that control muscle length and force, with final precise control being exerted through structures above the level of the medulla. 


Where do anaesthetics and muscle relaxants act upon?



Outline the 3 levels of integration from phylogenetically oldest to the newest

  • Spinal Level - Homeostasis, reflex actions. Simplest. Stereotyped behaviour. Basic locomotory circuits, postural control.
  • Subcortical Level - Primitive actions: securing food and water, reproduction
  • Cortical Level - highest level. Science, philosophy, art


Which of the neural structures was the first to evolve?

The spinal cord


What is the highest level of neural integration?

Cortical Level (cerebral cortex)


Describe the terminal of the motor nerve

loses its myelin sheath and divides into a number of synaptic boutons which terminate in the motor end plate where the muscle membrane is thickened to receive the nerve terminals


1. Describe the motor end plate



2. What type of Ach receptors are these?

  • Invaginates into junctional folds which increase the surface area for NT binding
  • These folds are lined with acetylcholine receptors
  • Can see clear vesicles in the axon terminal containing Ach 




  1. Where is Ach made?
  2. What is it concentrated into?
  3. What is it made from?
  4. What catalyses the reaction?

1. In the cytoplasm of the axon terminal

2. Vesicles (about 10,000 molecules per vesicle)

3. Choline + Acetyl Co-enzyme A

4. Choline Acetyltransferase


Outline the processes within Neuromuscular Transmission

  • Inpulse arriving at the end of the motor neuron opens the calcium channels 
  • Rapid Ca2+ influx into the pre-synaptic terminal causes exocytosis of the clear Ach vesicles and the release of Ach into the synpatic cleft
  • Ach diffuses to the muscle NICOTINIC receptors (about 15-40 million per NMJ) in the junctional folds
  • These receptors, when activated, open non-specific cation channels (K+, Na+, Ca++)
  • Na+ diffusing into the cell sets up the End Plate Potential 


What is the Ach release at rest?


What happens with the arrival of a nerve impulse?

Quantal release of 0.5mV in magnitude - this is called the called the Miniature end plate potential (MEPP)


arrival and concomitant Ca++ influx -  MEPPs become much larger, and with temporal summation become large enough to  depolarise the muscle fibre to +50mV and set up a propogated muscle action potential.




  1. On average, how many vesicles of Ach are released with each nerve impulse?
  2. How long elapsed between the arrival of a nerve signal at the motor end plate and intitiation of a muslce action potential?

1. 60 vesicles of Ach with each vesicle containing 10,000 molecules.

This total (60 x 10000molecules) is about 10 times the number of molecules needed to activate the post synaptic membrane, so a propogated impulse is regularly carried by a single nerve volley arriving at the bouton.  


2. 0.5msec


Excitation - Contraction Coupling

  1. How are Action potentials conducted from the sarcolemma to deep within the muscles?
  2. Explain the process of excitation-contraction coupling
  3. How is the contraction that occurs limited to one single muscle twitch which may be summated?

  1. By T Tubules (studded with voltage-gated Ca2+ channels
  2. The Ca2+ channels on the T tubule are coupled to ryanodine receptors on the sarcoplasmic reticulum which open ryanodine calcium channels on the SR, increasing intracellular Ca++ concentration thus initiating contraction. 

  3. A calcium pump quickly removes the cytoplasmic calcium back into the reticulum


Termination of the Signal

  1. What breaks down Ach (to ensure it only remains in the synapse for a few milliseconds?)
  2. How much Ach is there in an average terminal?

  1. acetylcholinesterase 
  2. Enough for about 3000 discharges so ach is constantly being replenished from recycled choline


What does acetylcholinesterase hydrolyse Acetylcholine into?

Choline and Acetate


Outline the ways in which NMJ action can be pharmacologically modulated?

Give examples

  • Reducing Ach release - Botulinus Toxin which halts vesicle fusion at the PreSM. Causes flaccid paralysis of muscles (useful for wrinkles - botox)
  • Altering Ach receptor binding - Curare, a competitive antagonist of nicotinic Ach recpetors used now as pancuronium, a muscle relaxant for surgery (also used in lethal injection)
  • Change activity of acetylcholinesterase - Increases Ach available at synapse.
    • Good = Acetylcholinesterase inhibitors cause prolonged action of Ach in the synaptic cleft - may be used to treat Myasthenia Gravis 
    • Bad (xs Ach effects) = Vomiting, diarrhoea, bronchoconstriction, bradycardia, spasms followed by paralysis


Explain what happens to the end-plate potential when

  1. Ach release is reduced
  2. Ach R binding is altered
  3. Acetylcholesterase activity is changed

  1. The amount of released Ach is smaller, failure to trigger action potential, end plate potential not positive enough

  2. The amount of released Ach unchanged, failure to trigger action potential, end plate potential not positive enough

  3. The amount of released Ach unchanged,

    life-time off ACh in cleft is prolonged, higher probability of binding to ACh receptor, multiple action potentials first, block later


Myasthenia Gravis

  1. What is it?
  2. Why is it caused?
  3. How is it treated?

  1. autoimmune disease, antibodies to muscle type of nicotinic acetylcholine receptors; muscle weakness and fatigue first affecting extraocular muscles, but eventually all muscles with possibly lethal consequences (respiratory failure). First sign = diplopia – double vision. Issues swallowing – asphyxiation

  2. Too few receptors available for binding unchanged quantities of acetylcholine. 

    End-plate potential too small to elicit

    action potential

  3. using acetylcholinesterase inhibitors


Lambert Eaton Syndrome

  1. What is it?
  2. How can it be alleviated?
  3. What is it associated with?
  4. What else can produce these symptoms?

1. autoimmune disease, antibodies against nerve terminal Ca2+ channel (in presynaptic membrane), poor ACh release

2. by repetitive stimulation of the nerve

3. Several cancers

4. Aminoglycoside antibiotics can also affect Ca++ channels 


The Motor Unit (basic unit of muscle control)

  1. What is it defined as?
  2. Outline Small and Large motor units


  1. one motor neuron and all of the fibres it innervates
  2. All of the fibres in one motor unit are of the same type.  Small motor units with one neuron innervating ~ 10 fibres produce small fine, well graded increments in force produced and are found in muscles where fine control is essential eg extraocular muscles, tongue, finger muscles.  They are also generally composed of fatigue resistant muscle fibre types.  Larger motor units (innervation ratio 1 nerve: 1000-2000 muscle fibres) are ideal for generating large forces for posture or locomotion (eg gastrocnemius or soleus).


  1. How is control of muscle force achievable?
  2. Which are the first fibres to be recruited?
  3. What about when more force is called for?

  1. by altering the number of motor units fired simultaneously
  2. those from the small motor units.  This allows very finely graded control at low forces.  These motor units are populated by fatigue-resistant fibres, which is appropriate since theyre almost always active in maintaining posture
  3. When more force is called for, the larger motor units are then recruited.  These are populated by strong but fatigue prone–fibres, again OK because they’re rarely active -> the SIZE PRINCIPLE


  1. Aside from altering the amount of motor units being fired at the same time, how else can force be modulated?
  2. Why are motor units generally fired asynhronously?
  3. Consider a muscle of 1000 motor units
    1. how can we vary force with recruitment?
    2. how can we vary force with frequency modulation?

  1. altering the frequency of stimulation of the motor units from 1:1000 Hz (temporal summation, frequency modulation, tetany). 
    1. 1Hz= minimal contraction, 1000Hz = maximal contraction
  2. contraction is smooth over the entire muscle and not jerky twitches
  3. 1000 motor units
    1. we can vary force from 1 – 1000 motor units fired
    2. Variation in EACH motor unit from 1-1000 Hz, therefore we can grade muscle force from 1 – (1000 X 1000 =) 1,000,000 times.  This enables the fine control. 

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