Effect of acerylcholinesterase inhibition

[XOT]

---

Members do not see this ad.

I came across a question from Princeton Review (hyperlearning) that does not make sense to me. I hope someone can clarify...

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

The answer they gave was B) be depolarized longer with each action potential.

For me, I thought the correct answer would be A) be depolarized by action potentials more frequently.

I am making this assumption based on the action potential time-frame. Should the neurotransmitters action on the ion channel have a specific time frame based on the property of the sodium channel? Does anyone know how the increased concentration of ACh will cause an increase in the length of the action potential? Would this not necessarily mean that the ion channel is open longer? But how is it kept open longer?

Also, would answer A not be possible because of the absolute refractory period and its restriction on generating more frequent action potentials?

Thank you to anyone that can help...

 

[monkeyvokes]

I came across a question from Princeton Review (hyperlearning) that does not make sense to me. I hope someone can clarify...

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

The answer they gave was B) be depolarized longer with each action potential.

For me, I thought the correct answer would be A) be depolarized by action potentials more frequently.

I am making this assumption based on the action potential time-frame. Should the neurotransmitters action on the ion channel have a specific time frame based on the property of the sodium channel? Does anyone know how the increased concentration of ACh will cause an increase in the length of the action potential? Would this not necessarily mean that the ion channel is open longer? But how is it kept open longer?

Also, would answer A not be possible because of the absolute refractory period and its restriction on generating more frequent action potentials?

Thank you to anyone that can help...

ACh not being cleared out by acetylcholine esterase would result in a longer depolarization. Keep in mind you've got nicotinic receptors all over the neuromuscular junction, and if ACh is around it will keep binding and letting sodium into the muscle cell.
In order to increase frequency, you'd want something that acts on the alpha motor neuron. Something that results in more frequent exocytosis of acetlycholine (a stronger signal occuring earlier than the chemical signals at the neuromusclar junction). In this scenario, you release a packet of ACh into the NMJ, cause a depolarization, ACh is cleared by ACh esterase, depol subsides, then another packet of ACh is released, etc. All happening over and over quickly.

 

[sps27]

I don't have TPR but if you refer to TBR, page 51 in book 1 bio, there is a passage based on this concept. After reading your question I read that passage again. And I thought of something. Perhaps cigarette smoking inhibits acetylcholinesterase and since the depolarization period is longer, smokers feel that alertness and high for a longer duration, not necessarily more frequently, but for a longer duration. Anways, I could be wrong but that is what I think.

 

[XOT]

Hey guys, thanks for your input.

monkeyvokes, I am a little confused by your reasoning. When you say "if ACh is around it will keep binding" would that not imply greater frequency, because the term "keep binding" would have a different meaning than "remains bound" to the receptor which in turn will allow the ion channel to remain open longer.

Also for your frquency analogy, whey must the pre-synaptic neuron continuoulsy release ACh to increase frequency? Why will the ACh that remain in the synaptic cleft (due to AChE inhibitor) not be able to continuously generate AP and thus increase frequency?

I am still confused by this question. The explanation they have is: "ACh will remain in the cleft longer, and sodium channels will remain open longer with each action potential that reaches the synapse. If the sodium channels are open longer, the depolarization of the post-synaptic membrane will last longer."

This explanation still does not answer why sodium channels stay open longer or why frequency of AP is not increased.

 

[onedirection]

Also more ACh in the bloodstream, i've seen questions ask about it so might as well throw it in

 

[monkeyvokes]

Hey guys, thanks for your input.

monkeyvokes, I am a little confused by your reasoning. When you say "if ACh is around it will keep binding" would that not imply greater frequency, because the term "keep binding" would have a different meaning than "remains bound" to the receptor which in turn will allow the ion channel to remain open longer.

I don't believe that every individual binding of ACh to nicotinic receptors results in a single depolarization, i think there are a large amount of these receptors that collectively depolarize the muscle fiber. If there is no enzymatic degredation occuring due to ACh esterase inhibition, then ACh is free to float around and maintain the depolarization until it diffuses away (I don't think reuptake occurs for ACh).

Also for your frquency analogy, whey must the pre-synaptic neuron continuoulsy release ACh to increase frequency? Why will the ACh that remain in the synaptic cleft (due to AChE inhibitor) not be able to continuously generate AP and thus increase frequency?

I don't think increasing frequency would be due to a continuous release, but a more frequent release.
If ACh remained in the cleft then why would the depolarization stop at all until it diffuses away?

I am still confused by this question. The explanation they have is: "ACh will remain in the cleft longer, and sodium channels will remain open longer with each action potential that reaches the synapse. If the sodium channels are open longer, the depolarization of the post-synaptic membrane will last longer."

This explanation still does not answer why sodium channels stay open longer or why frequency of AP is not increased.

Made up example: say 10,000 ACh molecules are released onto 1,000 nicotinic receptors. After 50 nicotinic receptors are opened, the muscle fiber is sufficiently depolarized. There is no acetylcholine esterase to break down ACh, so the muscle fiber stays depolarized until ACh slowly diffuses away.
Collectively, in this scenario sodium channels spend more time letting sodium into the muscle cell.