Acetylcholine is one of the most important and longest known neurotransmitters. Among other things, it directs muscle contraction and has an influence on blood pressure, alertness and digestion.
Acetylcholine Definition
First, the next paragraph should give you an overview of what acetylcholine actually is.
Acetylcholine, or ACh for short, is a neurotransmitter. This means that it takes on central tasks in the transmission of excitation. It occurs in both the central and peripheral nervous systems. Its functions include mediating muscle contraction and signaling in the autonomic nervous system.
Acetylcholine structure and synthesis
Acetylcholine is an ester of acetic acid and the amino alcohol choline.
Both choline and acetyl-CoA needed. Acetyl-CoA is, so to speak, an «activated» acetic acid residue, because the attached coenzyme A can transfer the acetyl group.
The reaction of the two components takes place in the end knobs of synapses and is controlled by the enzyme choline acetyltransferase catalyzed. The finished acetylcholine becomes a transporter in storage vesicles packed up.
The transporter that stores acetylcholine in vesicles is also called vesicular acetylcholine transporter (VAChT for short). This is a so-called antiporter, which means that two substances are transported in opposite directions. In VAChT, these are acetylcholine and protons.
Figure 1: Acetylcholine structure
The acetylcholine is thus temporarily stored in the nerve cell until it is required for the transmission of excitation. If necessary, it will eventually through exocytosis in the synaptic cleft poured out.
Choline is a biogenic amine, that is, it is formed by decarboxylation of amino acids. Neurotransmitters are very often based on biogenic amines, such as dopamine and serotonin.
Acetylcholine Occurrence
As previously mentioned, acetylcholine occurs both in the central nervous system (CNS), as well as in the peripheral nervous system (PNS) before.
In the PNS, acetylcholine is relevant for initiating muscle contraction. It will be about that neuromuscular junction poured out and thus transmits the signal to the muscles.
In addition to other neurotransmitters, it is also very common in the brain, i.e. in the CNS. There it takes on various functions in connection with attention and learning.
ACh is also particularly important in the vegetative or autonomic nervous system, i.e. in sympathetic and parasympathetic.
In both the sympathetic and parasympathetic nervous system, acetylcholine is the transmitter of all preganglionic neurons. in the parasympathetic he also takes over postganglionic the conduction of excitation. In the sympathetic nervous system, on the other hand, this task is almost always taken over by norepinephrine.
There is one exception where acetylcholine is used instead of norepinephrine even in sympathetic postganglionic neurons: the innervation of sweat glands.
acetylcholine effect
Its functions are as diverse as acetylcholine is found in the body. First, here is the process of excitation transmission with acetylcholine in the synapse:
- As described above, the fully synthesized acetylcholine is first packaged in vesicles and waiting to be used.
- Now come in action potential on, the vesicles are released into the synaptic cleft by exocytosis.
- At the postsynaptic membrane it interacts with different receptors accordingly also cholinoceptors to be named.
- Now, depending on the receptor to which the neurotransmitter binds, the signal is passed on in different ways.
That’s how it happens excitement or inhibition the subsequent cell.
Figure 2: Signaling with acetylcholine at a synapse
Also check out the articles on the subject of excitation transference. There you will learn more about synapses, action potential and much more!
Then, depending on the receptor and the site of action, acetylcholine can develop its various functions. This includes:
- initiation of muscle contraction (PNS),
- influence on blood pressure, heart rate, digestion and metabolism (Autonomic Nervous System),
- Control of various brain activities affecting Attention, learning, memory formation and more.
acetylcholine receptors
There are two different types of cholinoceptors in the postsynaptic membrane. They pass on the excitement in different ways.
Nicotinergic acetylcholine receptors
Are nicotinic acetylcholine receptors ligand-gated ion channels. That is, the receptor itself functions as a channel for ions and opens as soon as acetylcholine from the synaptic cleft binds.
When opened, positively charged sodium, potassium and calcium ions can pass through. The cell will depolarized and consequently aroused.
Figure 3: Nicotinergic acetylcholine receptor with its 5 transmembrane domains
Muscarinic acetylcholine receptors
Signal transmission works differently in the case of the muscarinic acetylcholine receptor. It’s about a G protein-coupled receptor. Depending on the type of G protein and its occurrence in the body, a distinction is made between different types, which are named M1-M5. When acetylcholine binds to a muscarinic receptor, a G protein is activated, causing Second messengers released and one signal cascade is set in motion.
As an example of a muscarinic receptor, one can look at the M2 receptor, which is found in the heart, for example. It is part of the parasympathetic innervation of the heart.
If the M2 receptors are activated by acetylcholine, a potassium channel opens after a signal cascade, allowing potassium to flow out of the excitatory heart cells. The cell hyperpolarizes.
The result is, among other things, a reduced heart rate. This makes sense if you remember that the parasympathetic system follows the principle of «rest and digest».
Figure 4: M2 receptor on the heart
In the classic signaling cascade in the autonomic ganglia, binding to an M1 cholinoceptor is followed by the activation of the so-called phospholipase C. This releases the second messengers IP3 and DAG, which leads to calcium influx. In contrast to the M2 cholinoceptor in the heart, postsynaptic excitation occurs.
You’re probably wondering where the receptors got their names from. Finally, «nicotinergic» is reminiscent of nicotine, which is known as an ingredient in tobacco. That’s right: the receptors were named after substances that also activate them. In the case of nicotinic receptors, this is indeed the case nicotinewith the muscarinic receptor that muscarine, the toadstool poison.
acetylcholine breakdown
What happens to the acetylcholine in the synaptic cleft when it is no longer needed?
That’s what the enzyme is for acetylcholinesterase essential. It breaks down the acetylcholine back into choline and acetic acid, rendering it ineffective. The choline returns to the synapse via a transporter. This is important because it is needed to synthesize new acetylcholine again.
Acetylcholine in medicine
In the meantime, a lot has been said about the so-called cholinergic system found out. It is well known how important the neurotransmitter is for the organism, so changes or other interventions can have serious consequences.
For example, there are some diseases associated with the cholinergic system.
is to be mentioned Alzheimerwho are deficient in acetylcholine. As a therapeutic approach, an attempt is made to acetylcholinesterase inhibitors counteract That is, you temporarily inhibit the enzyme that breaks down acetylcholine in the synaptic cleft. This ensures that the concentration of the neurotransmitter stays high enough to work.
Acetylcholine as an antidote
Another use of acetylcholinesterase inhibitors is as a antidote for the toxin curare. It is best known as «arrow poison», which was originally used for hunting in South America. It blocks the nicotinic cholinoceptors on muscle cells, thereby preventing breathing. However, if the breakdown of acetylcholine is disturbed, it «competes» with curare again for the binding sites and can displace it.
Also in case of poisoning with atropine acetylcholinesterase inhibitors are used. Like curare, it competes with acetylcholine for binding sites, but this time at muscarinic receptors, so the effects are partly different. Above all, atropine reduces the effect of the parasympathetic nervous system.
Atropine is also found in deadly nightshade. In Latin they are called «Atropa belladonna«. Belladonna is Italian for «beautiful woman».
The name probably derives from an earlier purpose: by inhibiting the parasympathetic nervous system, the pupils enlarge. This effect was often used for cosmetic purposes.
Negative aspects of acetylcholine
However, acetylcholinesterase inhibitors can also cause great harm by irreversibly inhibiting acetylcholinesterase. Examples of such substances are various chemical ones warfare agents as well as that insecticide parathion. Through them, the acetylcholine can no longer be rendered ineffective, so that it often leads to death overstimulation comes.
Even with autoimmune diseases Myasthenia gravis the effectiveness of acetylcholine is reduced. Antibodies destroy the cholinoceptors of the muscle cells. As a result, they can no longer be excited and the muscles lose their ability to contract.
Acetylcholine – The most important thing
- Acetylcholine is one of the most important neurotransmitters.
- It consists of acetic acid and choline, synthesis enzyme is choline acetyltransferase.
- Storage in vesicles in the end knobs of the synapses, exocytosis upon arrival of the action potential.
- Effect via nicotinic or muscarinic acetylcholine receptor.
- Important functions: initiating muscle contraction; Influence on blood pressure, heart rate, digestion and metabolism; Attention, learning, memory formation.
- Acetylcholinesterase inhibitors as a drug, insecticide and warfare agent.