Acetylcholine. ACh

Summary

This video provides an in-depth overview of acetylcholine, a key neurotransmitter involved in several physiological processes. It covers acetylcholine's synthesis from acetyl-CoA and choline, its storage in vesicles, release via action potentials, and its binding to nicotinic and muscarinic receptors. The breakdown of acetylcholine by acetylcholinesterase and its inhibition by certain drugs like organophosphates is discussed. Clinical correlations, such as Lambert-Eaton syndrome, botulism, and therapeutic uses of botulinum toxin, are highlighted. The video explains these mechanisms with clarity, making complex neurophysiological concepts more accessible.

Takeaways

• 🧠 Acetylcholine is a neurotransmitter derived from acetyl-CoA and choline, important in parasympathetic and somatic motor functions.
• ⚙️ Acetylcholine is synthesized by the enzyme choline acetyltransferase, which combines acetyl-CoA and choline, marking the neuron as cholinergic.
• 🚫 Hemicholinium blocks the choline transporter, preventing acetylcholine synthesis, leading to a lack of neurotransmitter storage and release.
• 📦 Acetylcholine is stored in vesicles via the vesicular acetylcholine transporter (VAChT), with each vesicle containing thousands of acetylcholine molecules.
• 🔋 Vesamicol inhibits VAChT, preventing acetylcholine from being stored in vesicles, disrupting its release into the synapse.
• ⚡ Acetylcholine is released when an action potential triggers calcium influx, causing vesicle fusion with the presynaptic membrane.
• 🦠 Diseases like Lambert-Eaton syndrome and botulism (caused by botulinum toxin) block acetylcholine release by affecting calcium channels or SNARE proteins, preventing vesicle fusion.
• 🔒 Acetylcholine binds to two main types of cholinergic receptors: nicotinic (on skeletal muscle and neurons) and muscarinic (found in the heart and other parasympathetic targets).
• ✂️ Acetylcholinesterase inactivates acetylcholine by breaking it down into acetate and choline, effectively ending the neurotransmitter's signal.
• 🧪 Acetylcholinesterase inhibitors, such as organophosphates, block acetylcholine breakdown, leading to an accumulation of acetylcholine in the synapse, causing overstimulation.

Q & A

What is acetylcholine?

Acetylcholine is a neurotransmitter derived from acetyl coenzyme A and choline. It is released by many neurons, including all parasympathetic neurons (preganglionic and postganglionic), sympathetic preganglionic neurons, and all somatic motor neurons at the neuromuscular junction, as well as various central nervous system neurons.

How is acetylcholine synthesized?

Acetylcholine is synthesized from acetyl coenzyme A (acetyl-CoA) and choline through the enzyme choline acetyltransferase. This process occurs in the terminal axon of neurons, where choline is transported into the cytoplasm by high-affinity choline transporters.

What happens if the choline transporter is blocked?

If the choline transporter is blocked by a drug like hemicholinium, choline cannot enter the neuron, preventing the synthesis of acetylcholine. As a result, there would be no acetylcholine available for storage and release.

How is acetylcholine stored in the neuron?

Acetylcholine is stored in vesicles within the terminal axon. It is transported from the cytoplasm into these vesicles by a protein called vesicular acetylcholine transporter (VAChT). Each vesicle contains thousands of acetylcholine molecules, and there are hundreds of thousands of vesicles per cholinergic neuron.

What clinical condition occurs when acetylcholine cannot be stored properly?

If acetylcholine storage is blocked by a drug like vesamicol, which inhibits the vesicular acetylcholine transporter, acetylcholine cannot be stored in vesicles. As a result, when the neuron tries to release acetylcholine, there will be little or none to release.

What triggers the release of acetylcholine from the neuron?

An action potential triggers the release of acetylcholine by causing an influx of calcium ions into the neuron. This influx leads to vesicle fusion with the presynaptic membrane, allowing acetylcholine to be released into the synaptic cleft.

How does botulinum toxin affect acetylcholine release?

Botulinum toxin cleaves the SNARE protein complex, preventing vesicles from fusing with the presynaptic membrane. As a result, acetylcholine cannot be released, leading to conditions such as botulism, which can cause paralysis and other serious effects.

What are the two main types of cholinergic receptors?

The two main types of cholinergic receptors are nicotinic receptors and muscarinic receptors. Nicotinic receptors are found on skeletal muscle and postganglionic neurons, while muscarinic receptors are found in various tissues innervated by parasympathetic neurons, as well as in sweat glands.

How is acetylcholine inactivated after its release?

Acetylcholine is inactivated by the enzyme acetylcholinesterase, which cleaves acetylcholine into acetate and choline. This process occurs rapidly, with the enzyme breaking down acetylcholine at a rate of about 1,000 molecules per second.

What happens when acetylcholinesterase is inhibited?

When acetylcholinesterase is inhibited by substances such as organophosphates or sarin gas, acetylcholine accumulates in the synapse. This leads to prolonged stimulation of cholinergic receptors, which can cause severe effects like muscle paralysis, respiratory failure, and even death.