Neuromuscular Junction Transmission Flashcards
Review: How many muscle fibers can a neuron activate? By how many neurons is one muscle fiber activated?
One motor neuron innervates multiple muscle fibers.
Each fiber is only innervated by one neuron.
What enzyme makes acetylcholine (ACh)? What is ACh made from?
Choline acetyl transferase. ACh is made from Acetyl CoA + choline.
How does ACh get into vesicles?
An ACh/H+ exchanger.
What are the three “stages” of ACh-containing vesicles in the pre-synaptic neuron? About how many of them are there in a resting neuron?
Immediate store (Primary -sitting on membrane, ready to release) - ~1000
Mobilization (can get to membrane in ~1sec) - ~10,000
Reserve - ~100,000
What three molecules mentioned are important for vesicle fusion / ACh release? (specify if on vesicle or cell membrane)
On vesicle: Synaptobrevin
On cell membrane: SNAP-25 and Syntaxin
Review: What ion induces vesicle fusion / ACh release?
Ca++
How many ACh-contaiing vesicles are released in a normal calcium influx?
about 20% of the immediate store -> ~200
What is Lambert-Eaton Myasthenia?
An autoantibody inhibits Ca++ channels in the pre-synaptic motor neuron and causes reduced ACh release.
How does muscle contraction get turned off? (2 ways)
Acetylcholinesterase breaks down ACh.
ACh is moved back into pre-synaptic neuron by Na+/ACh cotransporter.
How many molecules of ACh do you need to activate AChR?
- (but this is probably trivia)
Are there different fetal and adult ACh receptors?
Yes.
What happens if you get autoantibodies against MuSK?
Because MuSK is in a complex with AChR, antibodies against MuSK produce Myasthenia Gravis (which we learned about previously as Abs against AChR).
What enters the muscle cell when AChR ion channels are opened?
Na+
What happens when the threshold voltage is reached in muscle cells?
V-gated Na+ channels open -> AP -> contraction
How is the Safety Factor calculated?
End plate potential - (-50mV) = Safety factor
End plate potential must exceed -50mV in order to cause an AP in the muscle cell.
What is the CMAP?
Compound Muscle Action Potential - the sum of muscle action potentials detected with EMG
If you have impaired NMJ, what does your CMAP look like?
CMAP decreases with time, but levels off at about 1 second, when secondary ACh vesicles are utilized.
Who gets Lambert-Eaton Myasthenic Syndrome?
1/3: People with other autoimmune disease
2/3: People with squamous cell carcinoma
What part of a patient’s history would make you suspect an NMJ disorder?
Fluctuating symptoms: weakness that gets better or worse with use. (yes, many other things would make you suspicious, but go with it…)
Would you suspect and HMJ if a patient reported numbness?
No, because that would suggest that sensory nerves are involved as well.
How do botulinum toxin work?
Proteases that cleave SNAP-25 or Syntaxin on the pre-synaptic membrane -> no ACh release -> flaccid paralysis.
Contrast botulinum toxins with C. tetani toxins.
Tetanus toxin targets synaptobrevin, but acts on inhibitory axons in the spinal cord -> muscle contraction. Tetanus toxin doesn’t act at the NMJ.
How do organophosphorous gases kill you?
Activate V-gated Na+ channels on the muscle -> muscle depolarizes and can’t repolarize to produce APs -> paralysis. Paralysis of the diaphragm prevents breathing -> death.
What do physostigmine, neostigmine, and pyridostigmine do?
The -stigmine drugs (are broken down by acetylcholinesterase to metabolites that) inhibit acetylcholinesterase -> increased ACh in the NMJ. Good for things like myasthenia gravis.
Aside from auto-Abs directly blocking AChR in myasthenia gravis, how else do the Abs cause disease?
Abs -> inflammation -> reduced number of AChR molecules on and damage to the motor end-plate.
How do paralytics such as succinylcholine work?
Bind to AChR and keep in open -> Na+ comes in and depolarizes cell. Cell stays depolarized, no APs -> flaccid paralysis. (note it causes an initial contraction)
What is pancuronium? How does it work?
Paralytic used in surgery. Competitive inhibitor of AChR.
