THE NMJ

Question 1

define the neuromuscular junction

Answer 1

this is the area where a motor neuron and skeletal muscle come into contact
- it is a chemical synapse

Question 2

what are the 2 types of innervations

Answer 2

1. ocular muscles- these muscles need precise control so 1 motor unit per myofibril
2. lattisimus- these are larger muscles where 1 motor unit can innervate multiple fibrils

Question 3

difference between NMJ and a synapse

Answer 3

-a NMJ is between muscle and motor neuron whereas a synapse is between 2 neurons
-synapses dont always respond to the AP wherease NMJ always responds to the AP in the presynaptic neuron

Question 4

explain what the synaptic cleft is

Answer 4

it is the space between the presynaptic terminal and the motor end plate
-it is filled with ECF

Question 5

what can be found on the motor end plate

Answer 5

1. nicotinic cholinergic ligand gated channels
2. acetylcholinesterase

Question 6

explain the movement of the AP

Answer 6

1. first it moves from from the axon to the terminal bouton
2. once here the depolarization cause calcium channels to open and allow calcium to enter the terminal
3. the calcium binds to synaptic vesicles and; triggering exocytosis of Ach from the vesicles into the synaptic cleft.
   4.ach then binds to the receptors on the motor end plate and this allows sodium to enter the post synaptic membrane and K flows in the other direction
4. this entry of sodium triggers an end plate potential which travels up towards voltage gated sodium channels
5. these open and sodium flows into the motor end plate and triggers an action potential
6. the action potential travels towards the myofibrils T-Tubules and enters
7. entry causes the release of calcium which causes cross bridge binding and finally muscle contraction

Question 7

what does the nicotinic acetylcholine receptor look like

Answer 7

it has 4 subunits: 2 alpha, 1 beta and 1 gamma subunit
-the alpha subunits have the ach receptors

Question 8

what are the post synaptic potentials

Answer 8

-when sodium enters the motor end plate this leads to a depolarisation called an end plate potential
-the 2 types of end plate potentials are EPSPs and IPSPs( excitatory/inhibitory post synaptic potentials)

Question 9

EPSPs

Answer 9

-excitatory post synaptic potentials have no threshold and as more ach binds to the receptors; the bigger the depolarisation ie; EPSP becomes.
-depolarisation occurs because the influx of sodium is greater than the efflux of potassium so muscle becomes more positive
-the EPSP then will trigger opening of the voltage gated channels so an AP can be produced

Question 10

IPSPs

Answer 10

-inhibitory post synaptic potentials occur when neurotransmitters called GABA or glycine are released from the presynaptic terminal instead of ach
-these bind to receptors that when opened; allow CL- to enter the motor end plate and K+ to leave which leads to hyperpolarisation of the motor end plate
- so no AP is produced

Question 11

what does acetylcholinesterase do

Answer 11

-it degrades ONLY free ach in the synaptic cleft so as to recycle choline and acetate
-it will then transport choline back to the terminal of the neuron where it can bind with acetyl coA to make more Ach

Question 12

how to increase the rate

Answer 12

-would need more APs
-so more calcium can be released
-so more acetylcholine is released from vesicles
-so the depolarisation ie; end plate potential is greater

Question 13

explain how exocytosis from the synaptic vesicle occurs

Answer 13

1. so note that many of the synaptic vesicles are already bound to the presynaptic membrane via specialised sites.
2. the docking involves proteins on both membranes that make up the SNARE protein complex
   -on the vesicle there is synaptobrevin-2
   -on the plasma membrane there is syntaxin and SNAP-25
3. so when the calcium enters the terminal it will bind to synaptotagmin receptors on the vesicle
4. this binding causes fusion of the plasma membrane with the vesicle membrane via the SNARE proteins
5. so the ach molecules can be released

Question 14

3 mechanisms by which the synaptic vesicles are recycled

Answer 14

1. kiss and run
2. complete fusion
3. complete fusion with an endosome

Question 15

explain the kiss and run method

Answer 15

here the fusion pore directly closes and reformation of the vesicle occurs

Question 16

explain complete fusion

Answer 16

here the vesicle flattens and then the clathrin mediated endocytosis occurs where the clathrin coat is removed and the vesicle can return to the pool

Question 17

complete fusion + endosome

Answer 17

here the same happens but once endocytosis occurs; the coated vesicle first fuses to an endosome; then through budding of the endosome mature vesicles are produced into the pool

Question 18

what are the 3 chemical agents that affect the NMJ

Answer 18

1.botulinum
2. curare
3.black widow spider venom

Question 19

explain the actions of botulinum

Answer 19

• it is produced by bacteria and can be found in improperly canned foods
  -it is a neurotoxic protein
  -it will block the release of neurotransmitter ach from vesicles by blocking the SNARE complex proteins so exocytosis cannot occur
  -leads to botulism which is characterised by flaccid muscle paralysis where muscles cannot contract; if this occurs in the diaphragm it can be deadly
  -small amounts of botulinum is used in cosmetics like botox to stop the formation of wrinkles or smooth them out.

Question 20

explain the action of curare

Answer 20

it is a plant extract that is used in darts as it causes flaccid paralysis in their victims
-it also is used in anaesthesia as a muscle relaxant
- it basically competes with ach for the receptors and so the end plate potentials are smaller ie; smaller contraction

Question 21

explain how black widow spider venom works

Answer 21

• when infected it causes the hyper release of ach until it runs out; then muscle paralysis occurs

Question 22

which disease affects the NMJ

Answer 22

myasthenia gravis

Question 23

explain how myasthenia gravis works

Answer 23

• this disease is where your antibodies attack and destroy ach receptors on the motor end plate
  -so you see weakness in eyes; face and eyelids