Acetylcholinesterase questions

[smilealittle]

Say we have an acetylcholinesterase inhibitor at a neuromuscular junction. Since this would cause a buildup of acetylcholine, wouldn't we see an increase in the frequency of action potentials for the postsynaptic cell? Or would we NOT see an increase in frequency due to the fact that the cell is depolarized and can't repolarize to cause another action potential due to so much ACH causing an influx of Na+?

If an inhibitor of acetylcholinesterase is added to a neuromuscular junction, then the postsynaptic membrane will:

A. Be depolarized by action potentials more frequently
B. Be depolarized longer with each action potential.
C. Be resistant to depolarization
D. Spontaneously depolarize.

To me, A, B, & D could be true because a buildup of acetylcholine would cause all of these, including the cell depolarizing spontaneously without any stimulus.

The correct answer is "B", but I'm not completely confident as to why the other answers are wrong.

What exactly does acetylcholinesterase do to the post synaptic cell? Does it increase the frequency of action potentials that cell has? Say we are looking at the sympathetic nervous system. Would acetylcholinesterase at the first synapse (the nicotinic receptor) cause an increase in the release of norepi/epi at the second synapse (to the effector organ)?

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[Arayh]

Acetylcholinesterase normally sits in the synaptic junction and cleaves ACh, hence ending action potentials. Ach-esterase inhibitors such as Edrophonium are used to treat certain diseases such as myasthenia gravis. When you add an inhibitor, the ACh can stay there longer, open more channels and generate a "longer" action potential.

 

[smilealittle]

Acetylcholinesterase normally sits in the synaptic junction and cleaves ACh, hence ending action potentials. Ach-esterase inhibitors such as Edrophonium are used to treat certain diseases such as myasthenia gravis. When you add an inhibitor, the ACh can stay there longer, open more channels and generate a "longer" action potential.

Thanks so much for the answer, that makes sense. I think that is the conclusion I was coming to, but wasn't sure. So it probably wouldn't cause MORE action potentials or a higher FREQUENCY of action potentials because the cell is remaining depolarized, and it needs to repolarize before another action potential can happen, correct?

 

[Arayh]

Yes, the cell can only reach a certain frequency of action potentials, there is still the absolute refractory period that must happen.

 

[smilealittle]

Yes, the cell can only reach a certain frequency of action potentials, there is still the absolute refractory period that must happen.

Thanks so much. Then when you say the open channels (due to excess ACh) create a "longer" action potential, does that mean the absolute refractory period has increased (due to the inability to repolarize)?

 

[Arayh]

The absolute refractory period is a set measurement after the end of the last action potential. The length of it doesn't rise due to ACHesterase inhibitors. The last action potential is longer, the refractory period is just put off until the potential ends.

 

[Volvulus10]

Arayh is correct. A few other things I'd like to include for completion is that 1. edrophonium is not used to treat MG but is used more for the diagnosis (Tensilon test = edrophonium). The drug of choice (at least for the boards) is pyridostigmine, another AChE.

The second point and the point that the MCAT may or may not ask (too far removed for me to know the importance of) is that when a AchE inhibitor is used, the increase in ACh in the synaptic cleft actually leads to a downregulation of Ach receptors. The result is that more and more of the drug is eventually required.

A nice little "experimental" tidbit that the test could ask about is what happens with muscle stimulation in a patient w/ MG vs. someone with Lambert-Eaton myesthenic syndrome? With MG, stimulation leads to fatigue while someone with LES will actually GAIN muscle function.

 

[smilealittle]

Thanks so much for these responses, they helped a lot!