NMJ

Question 1

lower motor neurons innervate skeletal muslces (alpha-motor neurones)

where do you find the cell body of the motor unit of the NMJ? [1]

one alpha motor neuron innervates: [1]

• one muscle fibre
• a number of muscle fibres

Answer 1

where do you find the cell body of the motor unit of the NMJ? [1]
ventral (anterior) horn of the spinal cord

one alpha motor neuron innervates: [1]

• one muscle fibre
• *- a number of muscle fibres:** forms the motor end plate (presynaptic NMJ)

Question 2

label A

Answer 2

Question 3

synaptic terminal (bouton) has how many:

• mitchondria
• synaptic vesicles. what do they contain?

Answer 3

synaptic terminal (bouton) has how many:

• mitchondria: many - v metabolically active
• synaptic vesicles: many what do they contain: Ach

Question 4

what happens after Ach binds to Ach receptor?

Answer 4

• Ach binds to Ach-receptor
• opens Ach-receptor
• allows Na channel to open & Na goes through
• causes depolarisation of muscle membrane
• causes release of Calcium from sarcoplasmic reciticulum
  … other steps…
• muscle contraction

Question 5

NMJ: inside the axon terminal.

• where is Ach made?
• how is it made? [2] (which substrates [2] / enzymes [1] )

Answer 5

• where is Ach made?
• *inside presynaptic terminal**
• how is it made? (which substrates [2] / enzymes [1] )
• *- choline + acetyl coA** via choline acetyltransferase
• after binding to post synaptic receptor, acetylcholinesterase breaks Ach down into choline + acetyl coA
• choline reenters the presynaptic cleft & joins with a new acetyl CoA

Question 6

describe the mechanism of AP causing the release of ACh in presynaptic cleft? [4]

Answer 6

describe the mechanism of AP causing the release of ACh in presynaptic cleft? [4]

• Na+ AP in motor neuron gets to terminal bouton
• voltage gated Ca channel opens and calcium enters.
  i) continues depolarisation
  ii) caues release of synaptic vesicles
• Ca2+ causes docked vesciles to fuse with pre-synaptic membrane
• Ach vesicles release contetns into synaptic cleft, binds to Ach-receptor, Na+ goes in & depolarises
• causes muscle contraction

Question 7

Where do you find:

L type calcium channels [2]

N type calcium channels [1]

Answer 7

L type calcium channels [2]
heart
vascular smooth muscle

N type calcium channels [1]
pre-synaptic terminals - very close to the vesicles

Question 8

explain mechanism of docking at NMJ and release of Ach occurs at presynaptic vesicle

Answer 8

vesicles docks by:

• synaptobrevin interacts with syntaxin and SNAP25: holds the vesicle close to pre-synaptic membrane (but doesnt fuse) = docking.
• Ca2+ binds to synaptotagmin: interacts with SNAP25/ syntaxin complex and tightens interaction between the vesicle and presynaptic membrane complexs & causes it to merge & release of Ach = confirmational change occurs.

Question 9

how much EPSP of mV or more do we need for AP at NMJ? [1]

what is quantal release of Ach? [1]

Answer 9

how much EPSP of mV or more do we need for AP at NMJ? [1]
40mV

what is quantal release of Ach? [1]
every vesicle contains same amount of ACh: same amount of NM is released with each AP. get a 1:1 transmission of nerve & muscle.

Question 10

What are conotoxins? [1]

botulinum toxins

• from which bacteria? [1]
• how many neurotoxins? [1]
• what do each of the following cleave:
  i) BTA-A & E [1] ;
  ii) BTX-B, D & F [1]
  iii) BTX-C [1]

Answer 10

What are conotoxins? [1]
selectively block N-type presynaptic calcium blockers - not v therapeutically used tho !!

botulinum toxins

• from which bacteria: Clostridium botulinum
• how many neurotoxins: 7 neurotoxins
• what do each of the following cleave:
  i) BTA-A & E: cleaves SNAP 25
  ii) BTX-B, D & F: cleaves synaptobrevin
  iii) BTX-C: cleaves syntaxin

Question 11

why does botox only cause permenant change after repeated use? [2]

Answer 11

why does botox only cause permenant change after repeated use? [2]

• *- after 3/4 months after first time use: new NMJ is created
• repeated use: nerve stops putting out NMJs / isnt as big or as extensive**

Question 12

what is nicotinic Ach receptor structure like? [2]

how many Ach have to bind before the Ach-receptor opens? [2]

what is an end plate potential? [1]
at what point does an AP occur in muscle? [1]

Answer 12

what is nicotinic Ach receptor structure like? [2]

- 5 subunits: 2 identical alpha subunits, 1 beta, 1 delta (& 1 gamma or epsilon)

how many Ach have to bind before the Ach-receptor opens? [2]
2

what is an end plate potential? [1]
when Na+ move into the muscle & cause depol

at what point does an AP occur in muscle? [1]
- 40mV

Question 13

explain mechanism of how Ach is neutralised [3]

Answer 13

explain mechanism of how Ach is neutralised [2]

• *- ACh released from ACh-recptor
• Acetylcholinesterase(is embedded in muscle membrane)binds to Ach: breaks it down to choline and acetic acid**
• *- choline is taken back up into axon**

Question 14

why does acetylcholinesterase act very quickly on Ach? [1]

Answer 14

why does acetylcholinesterase act very quickly on Ach? [1]
prevents spontananous or contined activation of Ach-receptors

Question 15

(what is myasthenia gravis? )

(treatment)?

Answer 15

• antibodies attack the Ach-R: end point potential not large enough to trigger a muscle AP
  = weakness & fatigue
• treatment: acetylcholinesterase inhibitor: prevents breakdown of Ach, so hangs around longer and triggers ACh-R and creates AP

Question 16

what are the two types of NMJ blockers [2] explain them

Answer 16

What are the two types of NMJ blockers [2]:

1. D tubocuraine: non-depolarising muscle relaxant
blocks the nicotonic Ach-R & prevents AP occuring

• Acetylcholinesterase inhibitor works as an antidote to it
• *2. depolarisng muscle relaxant**
• stimulate Ach-R like Ach and activate muscle (muscle twitch)
• but **do not detach: no more Ach can bind (paralysis)
• even if membrane is repolarised (from Na channels / NaKATPase), the drug causes it to bedesensitised**
• but breaks down after a while, so not perm. paraylses

Question 17

which of the following is a competitve blocker:

non-depolarsing blocker
depolarising blocker

Answer 17

which of the following is a competitve blocker:

non-depolarsing blocker
depolarising blocker

Question 18

which of the following leads to a transient twitching of muscle:

non-depolarsing blocker
depolarising blocker

Answer 18

which of the following leads to a transient twitching of muscle:

non-depolarsing blocker
depolarising blocker

Question 19

which of the following leads to a Ach channel opening:

non-depolarsing blocker
depolarising blocker

Answer 19

which of the following leads to a Ach channel opening:

non-depolarsing blocker
depolarising blocker - but then continued binding makes imposs to cause impulses

Question 20

How do u monitor status of NMJ blockades?

Answer 20

deliver 4 supramaximal stimuli every 0.5 secs:

in normal person: get same height of activation of muscle contraction - look at ratio of height of First & Fourth muscle contraction. should be 1 in normal cuz same

in phase 1: ToF ratio: constant but diminished

Question 21

how do NMJ stimulants work? [1]

quick or slow reaction? [1]

are they constant or reversible [1]

Answer 21

how do NMJ stimulants work? [1]

• makes NMJ hyperactive: muscle goes into convulsions and then paralysis

quick or slow reaction? [1]
slowly reaction

are they constant or reversible [1]
can be either lol

Question 22

Question 23