NMJ Flashcards
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
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)
label A
synaptic terminal (bouton) has how many:
- mitchondria
- synaptic vesicles. what do they contain?
synaptic terminal (bouton) has how many:
- mitchondria: many - v metabolically active
- synaptic vesicles: many what do they contain: Ach
what happens after Ach binds to Ach receptor?
- 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
NMJ: inside the axon terminal.
- where is Ach made?
- how is it made? [2] (which substrates [2] / enzymes [1] )
- 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
describe the mechanism of AP causing the release of ACh in presynaptic cleft? [4]
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
Where do you find:
L type calcium channels [2]
N type calcium channels [1]
L type calcium channels [2]
heart
vascular smooth muscle
N type calcium channels [1]
pre-synaptic terminals - very close to the vesicles
explain mechanism of docking at NMJ and release of Ach occurs at presynaptic vesicle
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.
how much EPSP of mV or more do we need for AP at NMJ? [1]
what is quantal release of Ach? [1]
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.
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]
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
why does botox only cause permenant change after repeated use? [2]
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**
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]
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
explain mechanism of how Ach is neutralised [3]
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**
why does acetylcholinesterase act very quickly on Ach? [1]
why does acetylcholinesterase act very quickly on Ach? [1]
prevents spontananous or contined activation of Ach-receptors
(what is myasthenia gravis? )
(treatment)?
- 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
what are the two types of NMJ blockers [2] explain them
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
which of the following is a competitve blocker:
non-depolarsing blocker
depolarising blocker
which of the following is a competitve blocker:
non-depolarsing blocker
depolarising blocker
which of the following leads to a transient twitching of muscle:
non-depolarsing blocker
depolarising blocker
which of the following leads to a transient twitching of muscle:
non-depolarsing blocker
depolarising blocker
which of the following leads to a Ach channel opening:
non-depolarsing blocker
depolarising blocker
which of the following leads to a Ach channel opening:
non-depolarsing blocker
depolarising blocker - but then continued binding makes imposs to cause impulses
How do u monitor status of NMJ blockades?
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
how do NMJ stimulants work? [1]
quick or slow reaction? [1]
are they constant or reversible [1]
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
