The mechanism of functioning of the chemical synapse. The structure of chemical synapses

Structure of a chemical synapse

Scheme of the process of nerve signal transmission at a chemical synapse

Porocytosis hypothesis

There is significant experimental evidence that the transmitter is secreted into the synaptic cleft due to the synchronous activation of the hexagonal groups of MPV (see above) and the vesicles attached to them, which became the basis for formulating the hypothesis porocytosis(English) porocytosis). This hypothesis is based on the observation that vesicles attached to the MPV contract synchronously upon receiving an action potential and at the same time secrete the same amount of transmitter into the synaptic cleft each time, releasing only part of the contents of each of the six vesicles. The term “porocytosis” itself comes from the Greek words poro(meaning pores) and cytosis(describes the transport of chemical substances across the plasma membrane of a cell).

Most experimental data on the functioning of monosynaptic intercellular connections are obtained from studies of isolated neuromuscular contacts. As in interneuronal synapses, MPVs form ordered hexagonal structures in neuromuscular synapses. Each of these hexagonal structures can be defined as a “synaptomer” - that is, a structure that is an elementary unit in the process of transmitter secretion. The synaptomer contains, in addition to the pore cavities themselves, protein filamentous structures containing linearly ordered vesicles; the existence of similar structures has been proven for synapses in the central nervous system (CNS).

As mentioned above, the porocytosis mechanism generates a quantum of neurotransmitter, but without the membrane of the individual vesicle completely merging with the presynaptic membrane. Small coefficient of variation (<3 %) у величин постсинаптических потенциалов является индикатором того, что в единичном синапсе имеются не более 200 синаптомеров , каждый из которых секретирует один квант медиатора в ответ на один потенциал действия . 200 участков высвобождения (то есть синаптомеров, которые высвобождают медиатор), найденные на небольшом мышечном волокне, позволяют рассчитать максимальный квантовый лимит, равный одной области высвобождения на микрометр длины синаптического контакта , это наблюдение исключает возможность существования квантов медиатора, обеспечивающих передачу нервного сигнала, в объеме одной везикулы.

Comparison of porocytosis and quantum vesicular hypotheses

A comparison of the recently accepted TBE hypothesis with the porocytosis hypothesis can be made by comparing the theoretical coefficient of variation with the experimental coefficient calculated for the amplitudes of postsynaptic electrical potentials generated in response to each individual transmitter release from the presynapse. Assuming that exocytosis occurs at a small synapse containing about 5,000 vesicles (50 for every micron of synapse length), postsynaptic potentials would be generated by 50 randomly selected vesicles, giving a theoretical coefficient of variation of 14%. This value is approximately 5 times greater than the coefficient of variation of postsynaptic potentials obtained in experiments, thus, it can be argued that the process of exocytosis in the synapse is not random (does not coincide with the Poisson distribution) - which is impossible if explained within the framework of the TBE hypothesis , but is quite consistent with the porocytosis hypothesis. The fact is that the porocytosis hypothesis assumes that all vesicles associated with the presynaptic membrane release the transmitter simultaneously; at the same time, the constant amount of transmitter released into the synaptic cleft in response to each action potential (stableness is evidenced by the small coefficient of variation of postsynaptic responses) can well be explained by the release of a small volume of transmitter by a large number of vesicles - in this case, the more vesicles involved in the process, the The correlation coefficient becomes smaller, although this looks somewhat paradoxical from the point of view of mathematical statistics.

Classification

Chemical synapses can be classified according to their location and belonging to the corresponding structures:

  • peripheral
    • neuromuscular
    • neurosecretory (axo-vasal)
    • receptor-neuronal
  • central
    • axo-dendritic - with dendrites, including axo-spinous - with dendritic spines, outgrowths on dendrites;
    • axo-somatic - with the bodies of neurons;
    • axo-axonal - between axons;
    • dendro-dendritic - between dendrites;

Depending on the mediator, synapses are divided into

  • aminergic, containing biogenic amines (for example, serotonin, dopamine;
    • including adrenergic containing adrenaline or norepinephrine;
  • cholinergic, containing acetylcholine;
  • purinergic, containing purines;
  • peptidergic, containing peptides.

At the same time, only one transmitter is not always produced at the synapse. Usually the main pick is released along with another one that plays the role of a modulator.

By action sign:

  • stimulating
  • brake

If the former contribute to the occurrence of excitation in the postsynaptic cell, then the latter, on the contrary, stop or prevent its occurrence. Typically inhibitory are glycinergic (mediator - glycine) and GABAergic synapses (mediator - gamma-aminobutyric acid).

Some synapses have a postsynaptic seal, an electron-dense area made of proteins. Based on its presence or absence, synapses are distinguished as asymmetric and symmetric. It is known that all glutamatergic synapses are asymmetric, and GABAergic synapses are symmetrical.

In cases where several synaptic extensions come into contact with the postsynaptic membrane, multiple synapses are formed.

Special forms of synapses include spiny apparatus, in which short single or multiple protrusions of the postsynaptic membrane of the dendrite contact the synaptic extension. Spine apparatuses significantly increase the number of synaptic contacts on a neuron and, consequently, the amount of information processed. Non-spine synapses are called sessile synapses. For example, all GABAergic synapses are sessile.

Notes

Links

  • Savelyev A.V. Sources of variations in the dynamic properties of the nervous system at the synaptic level // Artificial intelligence. - NAS of Ukraine, Donetsk, 2006. - No. 4. - P. 323-338.

see also

They form bulbous thickenings called synaptic plaques.

The membrane of the synaptic plaque in the area of ​​the synapse itself is thickened as a result of compaction of the cytoplasm and forms a presynaptic membrane. The dendrite membrane in the area of ​​the synapse is also thickened and forms a postsynaptic membrane. These membranes are separated by a gap - the synaptic cleft 10 - 50 nm wide.

Since many ions are involved in the formation of the resting membrane potential, the equilibrium can be disturbed by changes in the conductivity of various ions. So, for example, with an additional outgoing current of K+ ions or with an incoming current of Cl- ions, the resting potential of the membrane can increase, which means that it is hyperpolarized. Membrane hyperpolarization is the opposite of excitation, i.e. certain chemical processes on the postsynaptic membrane can cause inhibition of the neuron. In this possibility one can see a significant evolutionary advantage of chemical synapses over electrical synapses.

It is quite obvious that the chemical processes very briefly presented in this section can be modified by means of other, again chemical, substances. This happens with the help of independent connections - neuromodulators.

Chemical processes in the synapse open up wide opportunities for pharmacological regulation and are the subject of numerous studies in order to search for endogenous compounds capable of modifying synaptic transmission in a given direction. Indeed, the action of many medications is based on their effect on synaptic conduction. This applies not only to psychotropic and narcotic substances. Many others, such as blood pressure-lowering drugs, also act indirectly through synapses. In addition, many poisons of plant and animal origin have a targeted effect on the chemical synapse.

And the target cell. In this type of synapse, the role of an intermediary (mediator) of transmission is played by a chemical substance.

Consists of three main parts: a nerve ending with presynaptic membrane, postsynaptic membrane target cells and synaptic cleft between them.

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    Now we know how nerve impulses are transmitted. Let it all start with the excitation of dendrites, for example this outgrowth of the neuron body. Excitation means the opening of membrane ion channels. Through channels, ions enter the cell or flow out of the cell. This can lead to inhibition, but in our case the ions act electrotonically. They change the electrical potential on the membrane, and this change in the area of ​​the axon hillock may be enough to open sodium ion channels. Sodium ions enter the cell, the charge becomes positive. This causes potassium channels to open, but this positive charge activates the next sodium pump. Sodium ions re-enter the cell, thus the signal is transmitted further. The question is, what happens at the junction of neurons? We agreed that it all started with the excitation of dendrites. As a rule, the source of excitation is another neuron. This axon will also transmit excitation to some other cell. It could be a muscle cell or another nerve cell. How? Here is the axon terminal. And here there may be a dendrite of another neuron. This is another neuron with its own axon. Its dendrite is excited. How does this happen? How does an impulse from the axon of one neuron pass to the dendrite of another? Transmission from axon to axon, from dendrite to dendrite, or from axon to cell body is possible, but most often the impulse is transmitted from the axon to the dendrites of the neuron. Let's take a closer look. We are interested in what is happening in the part of the picture that I will frame. The axon terminal and the dendrite of the next neuron fall into the frame. So here's the axon terminal. She looks something like this under magnification. This is the axon terminal. Here is its internal content, and next to it is the dendrite of a neighboring neuron. This is what the dendrite of a neighboring neuron looks like under magnification. This is what's inside the first neuron. An action potential moves across the membrane. Finally, somewhere on the axon terminal membrane, the intracellular potential becomes positive enough to open the sodium channel. It is closed until the action potential arrives. This is the channel. It allows sodium ions into the cell. This is where it all begins. Potassium ions leave the cell, but as long as the positive charge remains, it can open other channels, not just sodium ones. There are calcium channels at the end of the axon. I'll draw it pink. Here's a calcium channel. It is usually closed and does not allow divalent calcium ions to pass through. This is a voltage dependent channel. Like sodium channels, it opens when the intracellular potential becomes sufficiently positive, allowing calcium ions into the cell. Divalent calcium ions enter the cell. And this moment is surprising. These are cations. There is a positive charge inside the cell due to sodium ions. How does calcium get there? The calcium concentration is created using an ion pump. I have already talked about the sodium-potassium pump; there is a similar pump for calcium ions. These are protein molecules embedded in the membrane. The membrane is phospholipid. It consists of two layers of phospholipids. Like this. This looks more like a real cell membrane. Here the membrane is also double-layered. This is already clear, but I’ll clarify just in case. There are also calcium pumps here, which function similarly to sodium-potassium pumps. The pump receives an ATP molecule and a calcium ion, cleaves the phosphate group from ATP and changes its conformation, pushing calcium out. The pump is designed to pump calcium out of the cell. It consumes ATP energy and provides a high concentration of calcium ions outside the cell. At rest, the concentration of calcium outside is much higher. When an action potential occurs, calcium channels open and calcium ions from outside flow into the axon terminal. There, calcium ions bind to proteins. And now let's figure out what's going on in this place. I have already mentioned the word “synapse”. The point of contact between the axon and the dendrite is the synapse. And there is a synapse. It can be considered the place where neurons connect to each other. This neuron is called presynaptic. I'll write it down. You need to know the terms. Presynaptic. And this is postsynaptic. Postsynaptic. And the space between this axon and the dendrite is called the synaptic cleft. Synaptic cleft. It's a very, very narrow gap. Now we are talking about chemical synapses. Usually, when people talk about synapses, they mean chemical ones. There are also electric ones, but we won’t talk about them for now. We consider an ordinary chemical synapse. In a chemical synapse, this distance is only 20 nanometers. The cell, on average, has a width of 10 to 100 microns. A micron is 10 to the sixth power of meters. Here it's 20 over 10 to the minus ninth power. This is a very narrow gap when you compare its size to the size of the cell. There are vesicles inside the axon terminal of a presynaptic neuron. These vesicles are connected to the cell membrane from the inside. These are the bubbles. They have their own bilayer lipid membrane. Bubbles are containers. There are many of them in this part of the cell. They contain molecules called neurotransmitters. I'll show them in green. Neurotransmitters inside the vesicles. I think this word is familiar to you. Many medications for depression and other mental problems act specifically on neurotransmitters. Neurotransmitters Neurotransmitters inside the vesicles. When voltage-gated calcium channels open, calcium ions enter the cell and bind to proteins that retain the vesicles. The vesicles are held on the presynaptic membrane, that is, this part of the membrane. They are held in place by proteins of the SNARE group. Proteins of this family are responsible for membrane fusion. That's what these proteins are. Calcium ions bind to these proteins and change their conformation so that they pull the vesicles so close to the cell membrane that the vesicle membranes fuse with it. Let's take a closer look at this process. After calcium binds to SNARE family proteins on the cell membrane, they pull the vesicles closer to the presynaptic membrane. Here's a bottle. This is how the presynaptic membrane goes. They are connected to each other by proteins of the SNARE family, which attract the vesicle to the membrane and are located here. The result was membrane fusion. This causes neurotransmitters from the vesicles to enter the synaptic cleft. This is how neurotransmitters are released into the synaptic cleft. This process is called exocytosis. Neurotransmitters leave the cytoplasm of the presynaptic neuron. You've probably heard their names: serotonin, dopamine, adrenaline, which is both a hormone and a neurotransmitter. Norepinephrine is also a hormone and a neurotransmitter. All of them are probably familiar to you. They enter the synaptic cleft and bind to the surface structures of the membrane of the postsynaptic neuron. Postsynaptic neuron. Let's say they bind here, here and here with special proteins on the surface of the membrane, as a result of which ion channels are activated. Excitation occurs in this dendrite. Let's say that the binding of neurotransmitters to the membrane leads to the opening of sodium channels. The sodium channels of the membrane open. They are transmitter dependent. Due to the opening of sodium channels, sodium ions enter the cell, and everything repeats again. An excess of positive ions appears in the cell, this electrotonic potential spreads to the area of ​​the axon hillock, then to the next neuron, stimulating it. This is how it happens. It can be done differently. Let's say that instead of sodium channels opening, potassium ion channels will open. In this case, potassium ions will flow out along the concentration gradient. Potassium ions leave the cytoplasm. I'll show them with triangles. Due to the loss of positively charged ions, the intracellular positive potential decreases, making it difficult to generate an action potential in the cell. I hope this is clear. We started off excited. An action potential is generated, calcium flows in, the contents of the vesicles enter the synaptic cleft, sodium channels open, and the neuron is stimulated. And if potassium channels are opened, the neuron will be inhibited. There are very, very, very many synapses. There are trillions of them. The cerebral cortex alone is thought to contain between 100 and 500 trillion synapses. And that's just the bark! Each neuron is capable of forming many synapses. In this picture, synapses can be here, here and here. Hundreds and thousands of synapses on each nerve cell. With one neuron, another, a third, a fourth. A huge number of connections... huge. Now you see how complex everything that has to do with the human mind is. I hope you find this useful. Subtitles by the Amara.org community

Structure of a chemical synapse

In the synaptic extension there are small vesicles, the so-called presynaptic or synaptic vesicles containing either a mediator (a substance that mediates the transmission of excitation) or an enzyme that destroys this mediator. On the postsynaptic, and often on the presynaptic membranes, there are receptors for one or another mediator.

The similar size of presynaptic vesicles at all synapses examined (40–50 nanometers) was initially considered evidence that each vesicle is a minimal cluster whose release is required to produce a synaptic signal. Vesicles are located opposite the presynaptic membrane, which is due to their functional purpose for releasing the transmitter into the synaptic cleft. Also near the presynaptic vesicle there are a large number of mitochondria (producing adenosine triphosphate) and ordered structures of protein fibers.

Synaptic cleft- this is the space between the presynaptic membrane and the postsynaptic membrane, 20 to 30 nanometers wide, which contains pre- and postsynaptic connecting structures built from proteoglycan. The width of the synaptic gap in each individual case is due to the fact that the transmitter extracted from the presynapse must pass to the postsynapse in a time that is significantly less than the frequency of nerve signals characteristic of the neurons forming the synapse (the time it takes for the transmitter to travel from the presynaptic membrane to the postsynaptic membrane is on the order of several microseconds) .

Postsynaptic membrane belongs to the cell that receives nerve impulses. The mechanism for translating the chemical signal of the mediator into the electrical action potential on this cell is receptors - protein macromolecules built into the postsynaptic membrane.

Using special ultramicroscopic techniques, a fairly large amount of information on the detailed structure of synapses has been obtained in recent years.

Thus, an ordered structure of crater-like depressions with a diameter of 10 nanometers pressed inward was discovered on the presynaptic membrane. At first they were called synaptopores, but now these structures are called vesicle insertion sites (VAS). MPVs are collected in ordered groups of six separate depressions around the so-called compacted protrusions. Thus, condensed projections form regular triangular structures on the inner side of the presynaptic membrane, and MPVs are hexagonal, and are the sites where vesicles open and release transmitter into the synaptic cleft.

Mechanism of nerve impulse transmission

The arrival of an electrical impulse to the presynaptic membrane includes the process of synaptic transmission, the first stage of which is the entry of Ca 2+ ions into the presynapse through the membrane through specialized calcium channels localized at the synaptic cleft. Ca 2+ ions, using a mechanism that is still completely unknown, activate vesicles crowded at their attachment sites, and they release the transmitter into the synaptic cleft. The Ca 2+ ions that enter the neuron, after they activate the vesicles with the mediator, are deactivated in a time of about several microseconds, due to their deposition in the mitochondria and vesicles of the presynapse.

Transmitter molecules released from the presynapse bind to receptors on the postsynaptic membrane, as a result of which ion channels open in the receptor macromolecules (in the case of channel receptors, which is their most common type; for other types of receptors, the signal transmission mechanism is different). Ions that begin to enter the postsynaptic cell through open channels change the charge of its membrane, which is partial polarization (in the case of an inhibitory synapse) or depolarization (in the case of an excitatory synapse) of this membrane and, as a consequence, leads to inhibition or provocation of generation by the postsynaptic cell action potential.

Quantum vesicular hypothesis

Widespread until recently as an explanation for the mechanism of transmitter release from the presynapse, the hypothesis of quantum vesicular exocytosis (QVE) implies that a “packet”, or quantum, of the transmitter is contained in one vesicle and is released during exocytosis (in this case, the vesicle membrane merges with the cell presynaptic membrane ). This theory has long been the prevailing hypothesis - despite the fact that there is no correlation between the level of transmitter release (or postsynaptic potentials) and the number of vesicles in the presynapse. In addition, the KVE hypothesis has other significant shortcomings.

The physiological basis for the quantized release of a mediator should be the same amount of this mediator in each vesicle. The CBE hypothesis in its classical form is not adapted to describe the effects of quanta of different sizes (or different amounts of mediator) that can be released during one act of exocytosis. It should be taken into account that vesicles of different sizes can be observed in the same presynaptic bouton; in addition, no correlation was found between the size of the vesicle and the amount of mediator in it (that is, its concentration in the vesicles may also be different). Moreover, in a denervated neuromuscular synapse, Schwann cells generate a larger number of miniature postsynaptic potentials than is observed in the synapse before denervation, despite the complete absence in these cells of presynaptic vesicles localized in the region of the presynaptic bouton.

Porocytosis hypothesis

There is significant experimental evidence that the transmitter is secreted into the synaptic cleft due to the synchronous activation of the hexagonal groups of MPV (see above) and the vesicles attached to them, which became the basis for formulating the hypothesis porocytosis(eng. porocytosis). This hypothesis is based on the observation that vesicles attached to the MPV, upon receiving an action potential, contract synchronously and at the same time secrete the same amount of transmitter into the synaptic cleft each time, releasing only part of the contents of each of the six vesicles. The term “porocytosis” itself comes from the Greek words poro(meaning pores) and cytosis(describes the transport of chemical substances across the plasma membrane of a cell).

Most experimental data on the functioning of monosynaptic intercellular connections are obtained from studies of isolated neuromuscular contacts. As in interneuronal synapses, MPVs form ordered hexagonal structures in neuromuscular synapses. Each of these hexagonal structures can be defined as a “synaptomer” - that is, a structure that is an elementary unit in the process of transmitter secretion. The synaptomer contains, in addition to the pore cavities themselves, protein filamentous structures containing linearly ordered vesicles; the existence of similar structures has been proven for synapses in the central nervous system (CNS).

As mentioned above, the porocytosis mechanism generates a quantum of neurotransmitter, but without the membrane of the individual vesicle completely merging with the presynaptic membrane. A small coefficient of variation (less than 3%) in the values ​​of postsynaptic potentials is an indicator that a single synapse contains no more than 200 synaptomers, each of which secretes one quantum of transmitter in response to one action potential. The 200 release sites (i.e. synaptomers that release transmitter) found on a small muscle fiber allow the calculation of a maximum quantum limit of one release site per micrometer of synaptic contact length, this observation excludes the possibility of the existence of transmitter quanta providing nerve signal transmission in the volume one vesicle.

Comparison of porocytosis and quantum vesicular hypotheses

A comparison of the recently accepted TBE hypothesis with the porocytosis hypothesis can be made by comparing the theoretical coefficient of variation with the experimental coefficient calculated for the amplitudes of postsynaptic electrical potentials generated in response to each individual transmitter release from the presynapse. Assuming that exocytosis occurs at a small synapse containing about 5,000 vesicles (50 for every micron of synapse length), postsynaptic potentials would be generated by 50 randomly selected vesicles, giving a theoretical coefficient of variation of 14%. This value is approximately 5 times greater than the coefficient of variation of postsynaptic potentials obtained in experiments, thus, it can be argued that the process of exocytosis in the synapse is not random (does not coincide with the Poisson distribution) - which is impossible if explained within the framework of the TBE hypothesis , but is quite consistent with the porocytosis hypothesis. The fact is that the porocytosis hypothesis assumes that all vesicles associated with the presynaptic membrane release the transmitter simultaneously; at the same time, the constant amount of transmitter released into the synaptic cleft in response to each action potential (stableness is evidenced by the small coefficient of variation of postsynaptic responses) can well be explained by the release of a small volume of transmitter by a large number of vesicles - in this case, the more vesicles involved in the process, the The correlation coefficient becomes smaller, although this looks somewhat paradoxical from the point of view of mathematical statistics.

Classification

By mediator

  • aminergic, containing biogenic amines (for example, serotonin, dopamine);
    • including adrenergic containing adrenaline or norepinephrine;
  • cholinergic, containing acetylcholine;
  • purinergic, containing purines;
  • peptidergic, containing peptides.

At the same time, only one transmitter is not always produced at the synapse. Usually the main pick is released along with another one that plays the role of a modulator.

By action sign

  • stimulating
  • brake

If the former contribute to the occurrence of excitation in the postsynaptic cell, then the latter, on the contrary, stop or prevent its occurrence. Typically inhibitory are glycinergic (mediator - glycine) and GABAergic synapses (mediator - gamma-aminobutyric acid).

According to their location and affiliation with structures

  • peripheral
    • neuromuscular
    • neurosecretory (axo-vasal)
    • receptor-neuronal
  • central
    • axo-dendritic - with dendrites, including axo-spinous - with dendritic spines, outgrowths on dendrites;
    • axo-somatic - with the bodies of neurons;
    • axo-axonal - between axons;
    • dendro-dendritic - between dendrites;

Some synapses have a postsynaptic seal, an electron-dense area made of proteins. Based on its presence or absence, synapses are distinguished as asymmetric and symmetric. It is known that all glutamatergic synapses are asymmetric, and GABAergic synapses are symmetrical.

In cases where several synaptic extensions come into contact with the postsynaptic membrane, multiple synapses are formed.

Special forms of synapses include spiny apparatus, in which short single or multiple protrusions of the postsynaptic membrane of the dendrite contact the synaptic extension. Spine apparatuses significantly increase the number of synaptic contacts on a neuron and, consequently, the amount of information processed. Non-spine synapses are called sessile synapses. For example, all GABAergic synapses are sessile.

Depending on which neuron structures are involved in the formation of the synapse, axosomatic, axodendritic, axoaxonal and dendrodentritic synapses are distinguished. The synapse formed by the axon of a motor neuron and a muscle cell is called the end plate (neuromuscular junction, myoneural synapse). The essential structural attributes of a synapse are the presynaptic membrane, the postsynaptic membrane and the synaptic cleft between them. Let's take a closer look at each of them.

The presynaptic membrane is formed by the termination of the terminal branches of the axon (or dendrite in a dendrodendritic synapse). The axon extending from the body of the nerve cell is covered with a myelin sheath, which accompanies it throughout its entire length, right up to its branching into terminal terminals. The number of terminal branches of the axon can reach several hundred, and their length, now devoid of the myelin sheath, can reach several tens of microns. The terminal branches of the axon have a small diameter - 0.5-2.5 µm, sometimes more. The endings of the terminals at the point of contact have a variety of shapes - in the form of a club, a reticulate plate, a ring, or can be multiple - in the form of a cup, a brush. The terminal terminal may have several extensions that contact along the way with different parts of the same cell or with different cells, thus forming many synapses. Some researchers call such synapses tangents.

At the point of contact, the terminal terminal thickens somewhat and the part of its membrane adjacent to the membrane of the contacted cell forms the presynaptic membrane. In the zone of the terminal terminal adjacent to the presynaptic membrane, electron microscopy revealed an accumulation of ultrastructural elements - mitochondria, the number of which varies, sometimes reaching several dozen, microtubules and synaptic vesicles (vesicles). The latter come in two types - agranular (light) and granular (dark). The former have a size of 40-50 nm, the diameter of granular vesicles is usually more than 70 nm. Their membrane is similar to that of cells and consists of a phospholipid bilayer and proteins. Most of the vesicles are fixed to the cytoskeleton with the help of a specific protein - synapsin, forming a transmitter reservoir. A smaller part of the vesicles is attached to the inner side of the presynaptic membrane through the vesicle membrane protein - synaptobrevin and the presynaptic membrane protein - syntaxin. There are two hypotheses regarding the origin of vesicles. According to one of them (Hubbard, 1973), they are formed in the region of the presynaptic terminal from the so-called bordered vesicles. The latter are formed in the recesses of the cell membrane of the presynaptic terminal and merge into cisterns, from which vesicles filled with transmitter bud. According to another view, vesicles as membrane formations are formed in the soma of the neuron, transported empty along the axon to the region of the presynaptic terminal and there they are filled with transmitter. After the release of the mediator, the empty vesicles return to the soma by retrograde axonal transport, where they are degraded by lysosomes.

Synaptic vesicles are most densely located near the inner surface of the presynaptic membrane and their number is variable. The vesicles are filled with a mediator; in addition, so-called cotransmitters are concentrated here - protein substances that play a significant role in ensuring the activity of the main mediator. Small vesicles contain low molecular weight mediators, and large vesicles contain proteins and peptides. It has been shown that the mediator can also be located outside the vesicles. Calculations show that in the human neuromuscular junction the density of vesicles reaches 250-300 per 1 micron 2, and their total number is about 2-3 million in one synapse. One vesicle contains from 400 to 4-6 thousand transmitter molecules, which constitutes the so-called “transmitter quantum”, released into the synaptic cleft spontaneously or upon the arrival of an impulse along the presynaptic fiber. The surface of the presynaptic membrane is heterogeneous - it has thickenings, active zones where mitochondria accumulate and the density of vesicles is greatest. In addition, in the region of the active zone, voltage-dependent calcium channels were identified, through which calcium passes through the presynaptic membrane into the presynaptic zone of the terminal terminal. In many synapses, so-called autoreceptors are built into the presynaptic membrane. When they interact with transmitters released into the synaptic cleft, the release of the latter either increases or stops depending on the type of synapse.

The synaptic cleft is the space between the presynaptic and postsynaptic membranes, limited by the contact area, the size of which for most neurons varies within a few microns 2. The contact area can vary in different synapses, which depends on the diameter of the presynaptic terminal, the shape of the contact, and the nature of the surface of the contacting membranes. Thus, for the most studied neuromuscular synapses, it has been shown that the contact area of ​​one presynaptic terminal with the myofibril can be tens of microns 2 . The size of the synaptic cleft ranges from 20 to 50-60 nm. Outside the contact, the cavity of the synaptic cleft communicates with the intercellular space, thus, two-way exchange of various chemical agents is possible between them.

The postsynaptic membrane is the portion of the membrane of a neuron, muscle or glandular cell that is in contact with the presynaptic membrane. As a rule, the area of ​​the postsynaptic membrane is somewhat thickened compared to neighboring areas of the contacted cell. In 1959, E. Gray proposed dividing synapses in the cerebral cortex into two types. Type 1 synapses have a wider gap, their postsynaptic membrane is thicker and denser than that of type 2 synapses, the compacted area is more extensive and occupies most of both synaptic membranes.

Integrated into the postsynaptic membrane are protein-glycolipid complexes that act as receptors capable of binding to transmitters and forming ion channels. Thus, the acetylcholine receptor in the myoneural synapse consists of five subunits that form a complex with a molecular weight of 5000-30000 that penetrates the membrane. Calculation has shown that the density of such receptors can be up to 9 thousand per µm 2 of the surface of the postsynaptic membrane. The head of the complex, protruding into the synaptic cleft, has a so-called “recognition center”. When two molecules of acetylcholine bind to it, the ion channel opens, its internal diameter becomes passable for sodium and potassium ions, while the channel remains impassable for anions due to the charges present on its internal walls. The most important role in the processes of synaptic transmission is played by a membrane protein called G-protein, which, in combination with guanine triphosphate (GTP), activates enzymes that include second messengers - intracellular regulators.

Receptors of postsynaptic membranes are located in the so-called “active zones” of synapses and among them there are two types - ionotropic and metabotropic. In ionotropic receptors (fast), to open ion channels, their interaction with a mediator molecule is sufficient, i.e. the transmitter directly opens the ion channel. Metabotropic (slow) receptors got their name due to the peculiarities of their functioning. The opening of ion channels in this case is associated with a cascade of metabolic processes in which various compounds (proteins, including G-protein, calcium ions, cyclic nucleotides - cAMP and cGMP, diacetylglycerols) are involved, playing the role of secondary messengers. Metobotropic receptors are not themselves ion channels; they merely modify the functioning of nearby ion channels, ion pumps, and other proteins through indirect mechanisms. Ionotropic receptors include GABA, glycine, glutamate, and N-cholinergic receptors. Metabotropic - dopamine, serotonin, norepinephrine receptors, M-cholinergic receptors, some GABA, glutamate receptors.

Typically, receptors are located strictly within the postsynaptic membrane, so the influence of mediators is possible only in the area of ​​the synapse. It has been discovered, however, that a small number of acetylcholine-sensitive receptors are also present outside the neuromuscular synapse in the muscle cell membrane. Under some conditions (during denervation, poisoning with certain poisons), zones sensitive to acetylcholine can form outside the synaptic contacts on the myofibril, which is accompanied by the development of muscle hypersensitivity to acetylcholine.

Receptors sensitive to acetylcholine are also widespread in the synapses of the central nervous system and in peripheral ganglia. Excitatory receptors are divided into two classes, differing in pharmacological characteristics.

One of them is a class of receptors on which nicotine has effects similar to acetylcholine, hence their name - nicotine-sensitive (N-cholinergic receptors), the other class - sensitive to muscarine (fly agaric poison) are called M-cholinergic receptors. In this regard, synapses, where the main transmitter is acetylcholine, are divided into groups of nicotinic and muscarinic types. Within these groups, many varieties are distinguished depending on their location and features of functioning. Thus, synapses with H-cholinergic receptors are described in all skeletal muscles, in the endings of preganglionic parasympathetic and sympathetic fibers, in the adrenal medulla, and muscarinic synapses in the central nervous system, smooth muscles (in synapses formed by the endings of parasympathetic fibers), and in the heart.

Russian State University of Chemical Technology

them. D. I. Mendeleev

Task No. 22.1:

Synapses, structure, classification.

Physiological features of excitation in synapses.

Completed: student gr. O-36

Shcherbakov Vladimir Evgenievich

Moscow - 2004

A synapse is a morphofunctional formation of the central nervous system, which ensures the transmission of a signal from a neuron to another neuron or from a neuron to an effector cell (muscle fiber, secretory cell).

Classification of synapses

All CNS synapses can be classified as follows.

    By localization: central (brain and spinal cord) and peripheral (neuromuscular, neurosecretory synapse of the autonomic nervous system). Central synapses can in turn be divided into axo-axonal, axo-dendritic (dendritic), axo-somatic, and axo-spine synapse. (Most excitatory synapses are localized in dendritic processes containing a large amount of actin and called spines), dendro-dendritic, dendro-somatic, etc. According to G. Shepherd distinguishes between reciprocal synapses, sequential synapses and synaptic glomeruli (cells connected in various ways through synapses).

    According to development in ontogenesis: stable (for example, synapses of unconditioned reflex arcs) and dynamic, appearing in the process of individual development.

    By final effect: inhibitory and excitatory.

    According to the signal transmission mechanism: electrical, chemical, mixed.

    Chemical synapses can be classified:

a) according to the form of contact - terminal (flask-shaped connection) and transient (varicose dilation of the axon);

b) by the nature of the mediator - cholinergic (mediator - acetylcholine, ACh), adrenergic (mediator - norepinephrine, NA), dopaminergic (dopamine), GABAergic (mediator - gamma-aminobutyric acid), glycinergic, glutamatergic, aspartatergic, peptidergic (mediator – peptides, for example, substance P), purinergic (mediator – ATP).

Electrical synapses. The question about them is largely unclear. Many authors do not clearly differentiate the concepts of “electrical synapse” and “nexuses” (in smooth muscles, in the myocardium). It is now recognized that there are electrical synapses in the central nervous system. From a morphological point of view, an electrical synapse is a gap-like formation (slit dimensions up to 2 nm) with ion bridges-channels between two contacting cells. Current loops, in particular in the presence of an action potential (AP), almost unimpededly jump through such a gap-like contact and excite, i.e., induce the generation of an AP of the second cell. In general, such synapses (they are called ephapses) provide very rapid transmission of excitation. But at the same time, with the help of these synapses it is impossible to ensure unilateral conduction, since most of these synapses have bilateral conductivity. In addition, they cannot be used to force an effector cell (a cell that is controlled through a given synapse) to inhibit its activity. An analogue of the electrical synapse in smooth muscles and in cardiac muscle are gap junctions of the nexus type.

The structure of a chemical synapse (diagram in Fig. 1-A)

In structure, chemical synapses are the ends of an axon (terminal synapses) or its varicose part (passing synapses), which is filled with a chemical substance - a mediator. In the synapse, there is an iresynaptic element, which is limited by the presynaptic membrane, a postsynaptic element, which is limited by the postsynaptic membrane, as well as an extrasynaptic region and a synaptic cleft, the size of which is on average 50 nm. There is a wide variety in the names of synapses in the literature. For example, a synaptic plaque is a synapse between neurons, an end plate is the postsynaptic membrane of a myoneural synapse, a motor plaque is the presynaptic ending of an axon on a muscle fiber.

Presynaptic part

The presynaptic part is a specialized part of the neuron process terminal where synaptic vesicles and mitochondria are located. The presynaptic membrane (plasmolemma) contains voltage-gated Ca 2+ channels. When the membrane is depolarized, the channels open and Ca 2+ ions enter the terminal, triggering exocytosis of the neurotransmitter in the active zones.

Synaptic vesicles contain a neurotransmitter. Acetylcholine, aspartate and glutamate are found in round, light-colored vesicles; GABA, glycine – in oval; adrenaline and neuropeptides - in small and large granular vesicles. Fusion of synaptic vesicles with the presynaptic membrane occurs with an increase in the concentration of Ca 2+ in the cytosol of the nerve terminal. Prior to the fusion of synaptic vesicles and the plasmalemma, the process of recognition of the presynaptic membrane by the synaptic vesicle occurs through the interaction of membrane proteins of the SNARE family (synaptobrevin, SNAP-25 and syntaxin).

Active zones. In the presynaptic membrane, the so-called active zones are areas of membrane thickening in which exocytosis occurs. Active zones are located opposite clusters of receptors in the postsynaptic membrane, which reduces the delay in signal transmission associated with the diffusion of the neurotransmitter in the synaptic cleft.

Postsynaptic part

The postsynaptic membrane contains neurotransmitter receptors and ion channels.

Physiological features of excitation in synapses

Synaptic transmission is a complex cascade of events. Many neurological and mental diseases are accompanied by disruption of synaptic transmission. Various drugs affect synaptic transmission, causing an undesirable effect (for example, hallucinogens) or, conversely, correcting a pathological process (for example, psychopharmacological agents [antipsychotic drugs]).

Mechanism. Synaptic transmission is possible through the implementation of a number of sequential processes: synthesis of a neurotransmitter, its accumulation and storage in synaptic vesicles near the presynaptic membrane, release of the neurotransmitter from the nerve terminal, short-term interaction of the neurotransmitter with the receptor built into the postsynaptic membrane; destruction of the neurotransmitter or its capture by the nerve terminal. (diagram in Fig. 1.)

Neurotransmitter synthesis. The enzymes necessary for the formation of neurotransmitters are synthesized in the perikaryon and transported to the synaptic terminal along the axons, where they interact with the molecular precursors of neurotransmitters.

Neurotransmitter storage. The neurotransmitter accumulates in the nerve terminal, located inside synaptic vesicles along with ATP and some cations. The vesicle contains several thousand neurotransmitter molecules, which makes up a quantum.

Neurotransmitter quantum. The quantum size does not depend on impulse activity, but is determined by the amount of precursor entering the neuron and the activity of enzymes involved in the synthesis of the neurotransmitter.

Rice. 1. The mechanism of chemical transmission of impulses in the nerve synapse; from A to D – successive stages of the process.

Neurotransmitter secretion. When the action potential reaches the nerve terminal, the concentration of Ca 2+ in the cytosol sharply increases, synaptic vesicles merge with the presynaptic membrane, which leads to the release of neurotransmitter quanta into the synaptic cleft. A small amount of neurotransmitter is constantly (spontaneously) secreted into the synaptic cleft.

Interaction of a neurotransmitter with a receptor. After being released into the synaptic cleft, neurotransmitter molecules diffuse through the synaptic cleft and reach their receptors in the postsynaptic membrane.

Removal of a neurotransmitter from the synaptic cleft occurs due to diffusion, cleavage by an enzyme and excretion by uptake by a specific carrier. The short-term interaction of the neurotransmitter with the receptor is achieved by the destruction of the neurotransmitter by special enzymes (for example, acetylcholine - acetylcholinesterase). At most synapses, signal transmission ceases due to rapid uptake of the neurotransmitter by the presynaptic terminal.

Properties of chemical synapses

One-way conductivity is one of the most important properties of a chemical synapse. Asymmetry - morphological and functional - is a prerequisite for the existence of one-way conduction.

    The presence of a synaptic delay: in order for a transmitter to be released in the presynaptic area in response to the generation of an AP and a change in the postsynaptic potential (EPSP or IPSP) to occur, a certain time is required (synaptic delay). On average it is 0.2–0.5 ms. This is a very short period of time, but when it comes to reflex arcs (neural networks), consisting of many neurons and synaptic connections, this latency time is summed up and turns into a tangible value - 300 - 500 ms. In situations encountered on highways, this time turns into a tragedy for the driver or pedestrian.

    Thanks to the synaptic process, the nerve cell that controls a given postsynaptic element (effector) can have an excitatory effect or, conversely, an inhibitory effect (this is determined by a specific synapse).

    In synapses, there is a phenomenon of negative feedback - the antidromic effect. This means that a transmitter released into the synaptic cleft can regulate the release of the next portion of the transmitter from the same presynaptic element by acting on specific receptors of the presynaptic membrane. Thus, it is known that adrenergic synapses contain alpha 2-adrenergic receptors, interaction with which (norepinephrine binds to them) leads to a decrease in the release of a portion of norepinephrine when the next signal arrives at the synapse. Receptors for other substances are also found on the presynaptic membrane.

    The efficiency of transmission at a synapse depends on the interval of signals passing through the synapse. If this interval is reduced for some time (by increasing the frequency of impulse delivery along the axon), then to each subsequent AP the response of the postsynaptic membrane (EPSP or IPSP value) will increase (up to a certain limit). This phenomenon facilitates transmission at the synapse and enhances the response of the postsynaptic element (control object) to the next stimulus; it is called “relief” or “potentiation”. It is based on the accumulation of calcium inside the presynapse. If the signal repetition rate through the synapse is very high, then due to the fact that the transmitter does not have time to be destroyed or removed from the synaptic cleft, persistent depolarization or catholic depression occurs - a decrease in the efficiency of synaptic transmission. This phenomenon is called depression. If many impulses pass through the synapse, then ultimately the postsynaptic membrane can reduce the response to the release of the next portion of the transmitter. This is called the phenomenon of desensitization - loss of sensitivity. To a certain extent, desensitization is similar to the process of refractoriness (loss of excitability). Synapses are subject to a process of fatigue. It is possible that fatigue (a temporary drop in the functionality of the synapse) is based on: a) depletion of transmitter reserves, b) difficulty in releasing the transmitter, c) the phenomenon of desensitization. Thus, fatigue is an integral indicator.

Literature:

1. Agadzhanyan N.A., Gel L.Z., Tsirkin V.I., Chesnokova S.A. PHYSIOLOGY

PERSON. - M.: Medical book, N. Novgorod: NGMA Publishing House,

2003, chapter 3.

2. Green N., Stout W., Taylor D. Biology in 3 volumes. T.2: Transl. English/Ed. R. Soper. – 2nd ed., stereotypical – M.: Mir, 1996, pp. 254 – 256

3. Histology



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