I am currently studying Pharmacology and a question came to mind. We know that Acetylcholine is used as a neurotransmitter in the neuromuscular junction, both Sympathetic as Parasympathetic, but as I understand, correct me if I am wrong, they don't interfere with each other because of their locations being physically separated. My question is, could somehow occur the incomplete absorption of Acetylcholine in the receptor of the organ, let's say for a Parasympathetic response and it "leaked" to a nearby muscle or even into a Sympathetic receptor and create a involuntary movement for example?
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2 Answers
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The enzyme responsible for the breakdown of acetylcholine (Ach), i.e., acetylcholinesterase, rapidly degrades, and inactivates Ach in the synaptic cleft after release. This process is particularly fast, as the synapse has to be cleared of neurotransmitter for a next action potential to occur (Čolović et al., 2013). So no, Ach does not leak away under physiologiocal conditions (Fig. 1).
In fact, common cholinesterase inhibitors that lead to Ach buildup by inhibiting its degradation, do not cause involuntary muscle twitches (spasms) as side effect. However, they do evoke muscle cramps, but that is easily explained by the increased retention of Ach in the synaptic cleft, leading to prolonged muscle contraction.
Fig. 1. Cholinesterase is active in the synaptic cleft. source: Health & Fitness.
Reference
- Čolović et al., Curr Neuropharmacol (2013); 11(3): 315–35
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"So no, Ach does not leak away under physiologiocal conditions "
I beg to differ. During times of psychological stress, after a physical injury or infection, these can interfere with mitochondrial biogenesis and acetylcholine leak from the neuromuscular junction damaging the sarcoplasmic reticulum and creating a feed forward loop.
Even though the pathophysiology of myofascial trigger points is not fully understood, the hypothesis of acetylcholine leakage is mostly accepted. Indeed, leakage of acetylcholine leads to impairment of sarcoplasmic reticulum with following extensive calcium release, as well as secondary sarcomere contraction and cell membrane damage. It results in local vasoconstriction leading to ischemia and hypoxia [3, 4]. That is why acetylcholine leakage at the neuromuscular junction may be significant in the context of thermal imaging.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053472/
Myofascial Trigger Points Therapy Modifies Thermal Map of Gluteal Region Grzegorz Onik, Teresa Kasprzyk, [...], and Karolina Sieroń
Zhuang X, Tan S, Huang Q. Understanding of myofascial trigger points. Chin Med J 2014;127:4271–7.
Bron C, Dommerholt JD. Etiology of myofascial trigger points. Curr Pain Headache Rep 2012;16:439–44.
