Structural Organization and Transmission Stages
Morphologically, the contact zone consists of three basic elements. The presynaptic membrane is the sheath of the transmitting nerve ending. The synaptic cleft is a microscopic space separating the cells. The postsynaptic membrane is the region of the innervated tissue directly adjacent to the nerve ending.
The physiological process of signal transmission is divided into three consecutive phases:
- Presynaptic stage. Inside the ending, the chemical mediator is synthesized and stored in synaptic vesicles. An arriving nerve impulse causes membrane depolarization, which triggers exocytosis—the release of vesicle contents outward.
- Transit stage. Molecules of the chemical mediator diffuse through the aqueous medium of the synaptic cleft toward the receiving cell.
- Postsynaptic stage. The transmitter interacts with specific receptors on the membrane of the target organ. The result is a change in the activity of the effector cell: inhibition or enhancement of its function.
Classification and Localization of Cholinergic Structures
Depending on the chemical nature of the released substance, cholinergic (transmitter: acetylcholine) and adrenergic (transmitter: noradrenaline) contacts are distinguished. Pharmacological agents acting on the efferent system are also divided into two main groups by target type.
Signal transmission via acetylcholine occurs in a number of critical anatomical structures:
- In autonomic ganglia (transmission from preganglionic fibers).
- In internal organs (in the terminal zones of postganglionic parasympathetic nerves).
- In skeletal musculature (neuromuscular junctions).
- In the adrenal medulla.
- In the carotid bodies.
Life Cycle of Acetylcholine
The physiology of mediator turnover follows a strict sequence. Synthesis of molecules occurs in the cytoplasm of nerve terminals from acetyl-CoA and choline. The reaction is catalyzed by the enzyme choline acetyltransferase. The required choline is taken back up from the cleft into the neuron via Na+-dependent transport. The finished substance is stored inside vesicles.
The release process is triggered when the action potential reaches the axon terminal. Depolarization leads to the opening of voltage-gated calcium channels. The influx of $Ca^{2+}$ ions into the cytoplasm initiates the apposition and interaction of specific proteins: VAMPs (on vesicles) and SNAPs (on the cell membrane). Membrane fusion occurs, and acetylcholine is released into the cleft. This stage can be blocked pharmacologically: for instance, botulinum toxin destroys the fusion protein complex, while magnesium ions or aminoglycosides reduce calcium entry into the cell.
Upon entering the cleft, the neurotransmitter interacts with receptors on the postsynaptic side to conduct the impulse, as well as with receptors on the presynaptic membrane to control further substance release.
Enzymatic Inactivation of the Neurotransmitter
The action of acetylcholine is short-lived due to rapid neutralization systems. The primary pathway is hydrolysis. There are two types of enzymes with such activity:
- Acetylcholinesterase (true cholinesterase). Located directly within synapses, it ensures the rapid cleavage of the neurotransmitter into acetic acid and choline. The latter undergoes neuronal reuptake for reuse.
- Butyrylcholinesterase (pseudocholinesterase, false cholinesterase). Located outside synaptic contacts—in blood plasma, liver, and other tissues. It is capable of destroying acetylcholine upon its entry into the systemic circulation.
Briefly: answers to topical questions
What subtypes of cholinergic receptors are distinguished by their pharmacological sensitivity?
Based on pharmacological sensitivity to exogenous substances (alkaloids), two main subtypes of cholinergic receptors are distinguished, although endogenous acetylcholine acts on them identically.
- M-cholinergic receptors (muscarinic) have high selective sensitivity to muscarine. They are located on the postsynaptic membrane of effector organ cells.
- N-cholinergic receptors (nicotinic) are sensitive to nicotine. They are localized in autonomic ganglia, the adrenal medulla, carotid bodies, the CNS, and skeletal muscles.
What is the mechanism of action of noradrenaline in adrenergic synapses?
The mechanism of action of noradrenaline in adrenergic synapses is associated with its release from postganglionic sympathetic endings, where it acts as a neurotransmitter, and its interaction with adrenergic receptors. Adrenergic receptors belong to G protein-coupled receptors.
Confirmed elements of adrenergic transmission:
- α₁-adrenergic receptors are located on the postsynaptic membrane of vascular smooth muscle; the interaction of catecholamines with these receptors is associated with vascular effects.
- α₂-adrenergic receptors may be located presynaptically; their blockade enhances neurotransmitter release.
- β₂-adrenergic receptors on the endings of adrenergic fibers may participate in the presynaptic regulation of noradrenaline release.
Inactivation of noradrenaline is carried out by the enzymes COMT and MAO.
To remember the components of acetylcholine synthesis: "Acetyl-CoA + Choline form the neurotransmitter, and the enzyme simply combines these words, adding the suffix '-transferase' — choline acetyltransferase."
Class and exam questions
What is exocytosis in the nerve terminal?
This is the process by which synaptic vesicles fuse with the presynaptic membrane and release their contents into the synaptic cleft. It is triggered when calcium ions enter the cytoplasm of the nerve terminal following membrane depolarization.
How does acetylcholine inactivation occur?
The neurotransmitter undergoes hydrolysis by the enzyme acetylcholinesterase to form choline and acetic acid. The resulting choline is taken back up into the nerve ending for reuse.
What substances are capable of blocking the exocytosis of acetylcholine?
Botulinum toxin prevents the interaction of vesicular and presynaptic membrane proteins. The process is also inhibited by substances that decrease calcium entry into the cell, such as magnesium ions and aminoglycoside antibiotics.
What else to study on this topic
- The role of VAMP and SNAP proteins in the process of vesicular membrane fusion
- The mechanism of action of voltage-gated calcium channels in the presynaptic membrane
- Differences between true cholinesterase and pseudocholinesterase: functions and localization
- Mechanisms of neuronal choline reuptake (Na+-dependent transport)
- Regulatory role of presynaptic cholinergic receptors in modulating neurotransmitter release
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