Acetylcholine
Acetylcholine (ACh) is a crucial neurotransmitter in both the central and peripheral nervous systems, playing a vital role in transmitting signals between nerve cells and muscles. Structurally, it is composed of acetic acid and choline. Acetylcholine is primarily synthesized in nerve terminals and is released at neuromuscular junctions, autonomic ganglia, and various synapses within the central nervous system. Initially identified by scientists Sir Henry Hallett Dale and Otto Loewi in the early 20th century, its discovery marked a significant advancement in neurobiology, earning both researchers the Nobel Prize in Physiology and Medicine in 1936.
Acetylcholine functions by binding to specific receptors, which are classified into two main types: nicotinic and muscarinic. These interactions can elicit either excitatory or inhibitory responses, depending on the receptor type and the context of the signaling. A decrease in acetylcholine levels is linked to various clinical conditions, such as Alzheimer’s disease and Myasthenia Gravis, highlighting its importance in both motor function and cognitive processes. Overall, acetylcholine's multifaceted roles underline its significance in maintaining both motor control and cognitive health.
On this Page
Acetylcholine
Acetylcholine, a chemical in the body, is classified as a neurotransmitter. Acetylcholine is abbreviated as ACh for scientific purposes. Structurally, acetylcholine is constituted by a chemical compound of acetic acid and choline. The name is therefore derived from this chemical makeup. Originally it was determined as an imitator of the vagus nerve given its propensity to create an electrical stimulus, yet its sites and purpose became evident as being more largely present. Acetylcholine is the neurotransmitter located at the sites of autonomic ganglia, neuromuscular junctions, central nervous system synapses, and autonomic innervated organs. A complex chemical reaction ensues giving rise to a process of synthesis, including a secretion of acetylcholine that has been stored in the body, an interaction with ACh receptors, and finally, a termination of the acetylcholine cycle.
![Acetylcholine pathway. By BruceBlaus (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons 87322209-114509.jpg](https://imageserver.ebscohost.com/img/embimages/ers/sp/embedded/87322209-114509.jpg?ephost1=dGJyMNHX8kSepq84xNvgOLCmsE2epq5Srqa4SK6WxWXS)
![Diagram of processes in a cholinergic synapse. By user:Pancrat (File:Synapse acetylcholine.png) [GFDL 1.2 (http://www.gnu.org/licenses/old-licenses/fdl-1.2.html)], via Wikimedia Commons 87322209-114510.jpg](https://imageserver.ebscohost.com/img/embimages/ers/sp/embedded/87322209-114510.jpg?ephost1=dGJyMNHX8kSepq84xNvgOLCmsE2epq5Srqa4SK6WxWXS)
Background
The presence of acetylcholine as a chemical mediator was discovered by Sir Henry Hallett Dale (1875-1968) in 1914. Dale determined that this action of chemical mediation by acetylcholine was essential in order for the electrical impulses to be transmitted from a nerve to a muscle in the body. The impulse causes a chain of reactions, including the release of acetylcholine. The discovery of acetylcholine was celebrated as the first time a neurotransmitter had been identified. Otto Loewi (1873-1961) confirmed the existence of acetylcholine during his studies. In 1936, both Dale and Loewi were awarded the Nobel Prize in Physiology and Medicine for the discovery and identification of acetylcholine.
Acetylcholine, one of the most important chemical messengers in the body, is found in the central nervous system and peripheral nervous system. In the central nervous system, the actions of acetylcholine have an effect on brain systems controlling arousal, attention, and motivation. Acetylcholine functions as a type of neuromodulator in the brain, modulating between neurons, rather than directly engaging in interneuron synaptic transmission. A primary function is its role as a neurotransmitter, and this is carried out as part of the central nervous system. Acetylcholine’s purpose as a neurotransmitter within the peripheral nervous system is conducted as the main aspect of the autonomic nervous system. In this case, the release of acetylcholine propels muscle action. A further dynamic interaction of acetylcholine in the peripheral nervous system pertains to controlling functions indicative of the sympathetic and parasympathetic systems. A significant interplay is its action as a neurotransmitter transmitting signals or impulses between motor nerves and the skeletal muscles required for manifesting as action. When the brain emits a signal that a body part needs to move, acetylcholine comes into play as a neurotransmitter, sending the signal to neuromuscular junctions. This sets off the intended action of the specific muscle required to perform the bodily action. When drugs are used that negatively interact with the neurotransmitter acetylcholine, a person's movement may be impeded because of the cessation or limitation of the neurotransmitter functioning appropriately. This can occur likewise when inhaling a nerve gas substance or pesticide.
Overview
Acetyl coenzyme A, termed Acetyl CoA, is a coenzyme that is synthesized from glucose during cellular respiration. Acetylcholine is then synthesized from Acetyl CoA. The location where the synthesis takes place is in the nerve terminals or neuromuscular junctions at various points within the central nervous system. Specifically, the originating point is at synapses found in the ganglia of the visceral motor system. Synapses are the junctions where the terminal of one neuron or presynaptic cell meet with a postsynaptic cell. When the nerve impulse arrives at the presynaptic terminal, a neurotransmitter is released, as it does at the neuromuscular junction point. Acetylcholine is one of the neurotransmitters identified as such. There are particular criteria that classify a substance as a neurotransmitter. These include the necessity for enzymes being present to facilitate a process of synthesis and a mechanism that is set in place, so that the synthesis action has a beginning and end. Additionally, a chemical reaction needs to occur at the receptor site when the transmitter is released, and a clearly identifiable response is obvious. Norepinephrine is another neurotransmitter fitting the criteria; yet while there are other neurotransmitters such as dopamine or serotonin, these do not necessarily meet all the classifications as in acetylcholine or norepinephrine. Neurotransmitters are synthesized continuously in cytoplasm of synaptic knobs, also known as presynaptic terminals. Research has shown that repetitive stimulation may increase the number of presynaptic terminals, which has an impact on the store and release of transmitter substances.
There are two types of neurotransmitters, classified according to their functional capacities. Excitatory neurotransmitters or inhibitory neurotransmitters have either an excitatory or inhibitory effect on the neuron with which they come into contact. Acetylcholine is an example of a neurotransmitter that is both excitatory and inhibitory. In its excitatory role, the neurotransmitter increases the stimulus potential of the neuron to manifest as action potential. The inhibitory role of the neurotransmitter translates as a decrease in stimulus to action potential. When a neurotransmitter such as acetylcholine exhibits both functional potentialities, which aspect becomes dominant depends on the type of receptor that is present. ACh receptors or cholinergic receptors are classified according to two types, nicotinic and muscarinic. The nicotinic ACh receptor is an ion channel, located in the neuromuscular junction, the autonomic ganglia, as well as to a lesser extent in the central nervous system. The muscarinic ACh receptors are typified as G protein coupled receptors and are found at automatically innervated visceral organs of the parasympathetic system and additionally in the sweat glands, the piloerector muscles, and in postsynaptic and presynaptic sections of the central nervous system.
Clinical effects marked by a decreased level of acetylcholine in the body include the possibility of Alzheimer's disease, and Myasthenia Gravis. In the case of Alzheimer's disease and dementia, a substantial reduction in the concentration of acetylcholine supplies in the cerebral cortex and the caudate nucleus has been established. Myasthenia Gravis is a disease of the neuromuscular junction. In this instance, the person's own antibodies destroy the ACh receptors.
Bibliography
"Acetylcholine." NCBI. Neuroscience. 2nd edition. Sinauer Associates, Inc., 2001. Web. 7 June 2016.
Cherry, Kendra. "What Is Acetylcholine?" Verywell. Verywell, 25 April 2016. Web. 7 June 2016.
Cherry, Kendra. "What Is a Neurotransmitter?" Verywell. Verywell, 26 April 2016. Web. 7 June 2016.
Daniels, Chris. "How to Increase Acetylcholine." SFGate. Demand Media, n.d. Web. 7 June 2016.
Henderson, Jane. "Acetylcholine Deficiency – How to Increase Acetylcholine." Get Help for Depression. Get Help for Depression, 2012. Web. 7 June 2016.
Jacob, Stanley, Clarice Ashworth Francone, Walter J. Lossow. Structure and Function in Man. London: Elsevier Health Sciences, 1982. Print.
Matityahu, Lior. "Acetylcholine Waves and Dopamine Release in the Striatum." Nature Communications, vol. 14, no. 6852, 27 Oct. 2023, doi.org/10.1038/s41467-023-42311-5. Accessed 15 Nov. 2024.
May, Paul. "Acetyl Coenzyme A." Bristol University. Bristol University, n.d. Web. 7 June 2016.
McDowall, Jennifer. "Acetylcholine Receptors." InterPro. InterPro, n.d. Web. 7 June 2016.
"Otto Loewi – Biographical." Nobelprize.org. Nobel Media, 2014. Web. 7 June 2016.
"Sir Henry Dale – Biographical." Nobelprize.org. Nobel Media, 2014. Web. 7 June 2016.
Waymire, Jack C. "Chapter 11: Acetylcholine Neurotransmission." Neuroscience Online. UTHealth, The University of Texas Medical School, 1997. Web. 7 June 2016.
"What are Neurotransmitters?" Neurogistics. Neurogistics, 2015. Web. 7 June 2016.