Concept of the Chemical Synapse
Synapse is a specialized structure that ensures signal transmission from one cell to another: from neuron to neuron, from neuron to a muscle fiber, or to an internal organ cell. According to the method of signal transmission, synapses are divided into electrical and chemical.
In a chemical synapse, the signal is transmitted via a specific chemical substance called a neurotransmitter. Neurotransmitters can be acetylcholine, adrenaline, noradrenaline, serotonin, and many other compounds. It is the use of the neurotransmitter that determines the name of the synapse.
Structure of a Chemical Synapse
Several key structures are distinguished within a chemical synapse:
- Presynaptic membrane — the membrane of the axon terminal of the transmitting neuron.
- Synaptic cleft — the space between the two membranes through which the neurotransmitter diffuses.
- Postsynaptic membrane — the membrane of the target cell (neuron, myocyte, organ cell).
- Vesicles containing the neurotransmitter — membrane organelles in the presynaptic terminal containing a large amount of the neurotransmitter.
- Receptors on the postsynaptic membrane specific to the given neurotransmitter (e.g., acetylcholine receptors).
Stages of Synaptic Transmission
- An action potential propagates along the presynaptic fiber.
- During depolarization, voltage-gated calcium channels open, and Ca²⁺ enters the presynaptic terminal down its concentration gradient (calcium is predominantly an extracellular cation).
- Calcium interacts with vesicle membrane proteins, ensuring their unanchoring from the cytoskeleton and movement toward the presynaptic membrane.
- The vesicle fuses with the presynaptic membrane, resulting in the exocytosis of the neurotransmitter into the synaptic cleft.
- The neurotransmitter diffuses across the cleft and binds to its receptor on the postsynaptic membrane.
- Receptor activation leads to the opening of ion channels and the influx of Na⁺ into the cell, which causes depolarization of the postsynaptic membrane.
Important: the action potential on the postsynaptic membrane is not formed immediately. First, a local excitatory postsynaptic potential (EPSP) arises. Several EPSPs must summate, and only after reaching the critical depolarization threshold is a full-fledged action potential generated.
Types of Postsynaptic Receptors
Receptors of the postsynaptic membrane are divided into two large groups:
- Ionotropic receptors — transmembrane proteins that combine the function of a receptor and an ion channel. Upon neurotransmitter binding, the protein changes conformation, and a channel opens within it (e.g., a sodium channel). Sodium enters the cell, and the membrane depolarizes. Transmission is rapid.
- Metabotropic receptors — transmembrane proteins coupled to a G protein. Receptor activation triggers a system of second messengers that alter intracellular metabolism; ion channels also subsequently open, leading to depolarization. Transmission is slower, but the effect is more prolonged.
Receptor Localization:
- Nicotinic acetylcholine receptor at the neuromuscular junction is ionotropic.
- Muscarinic acetylcholine receptor, adrenergic, serotonergic, and most other CNS receptors are metabotropic.
Neurotransmitter Utilization
After interacting with the receptor, the neurotransmitter must be removed from the synaptic cleft; otherwise, the signal cannot terminate. Various mechanisms exist: enzymatic degradation, reuptake, diffusion.
Using acetylcholine as an example: the enzyme acetylcholinesterase is located in the region of the postsynaptic membrane, breaking down acetylcholine into choline and an acetic acid residue. These products return to the presynaptic terminal, where new acetylcholine is resynthesized from them and reloaded into vesicles.
Clinical and Pharmacological Significance
Knowledge of the mechanisms of synaptic transmission forms the basis of action for many medicinal products. For example, acetylcholinesterase inhibitors reduce the breakdown of acetylcholine in the synaptic cleft, prolonging its action on receptors and enhancing cholinergic transmission.
A representative of this group is galantamine, used in neurodegenerative diseases, specifically in Alzheimer's disease, where prolonging the activity of cholinergic synapses in the CNS is required. Similar principles underlie the action of muscle relaxants, sympathomimetics, antidepressants, and many other classes of drugs affecting the stages of synaptic transmission.
Key points
- A chemical synapse transmits a signal between cells using a neurotransmitter.
- Structural elements: presynaptic membrane, synaptic cleft, postsynaptic membrane, vesicles, and receptors.
- The triggering factor for neurotransmitter exocytosis is the influx of Ca²⁺ through voltage-gated channels.
- EPSPs are formed first on the postsynaptic membrane, and only their summation generates an action potential.
- Ionotropic receptors are ion channels themselves; metabotropic receptors act via a G protein and second messengers.
- The nicotinic ACh receptor of the neuromuscular junction is ionotropic; the muscarinic receptor is metabotropic.
- Acetylcholinesterase breaks down acetylcholine into choline and acetic acid, followed by resynthesis in the presynaptic terminal.
- Acetylcholinesterase inhibitors (galantamine) are used in Alzheimer's disease to prolong cholinergic transmission.