Cholinergic synapses: structure, functions

Cholinergic synapses are a place in which two neurons or neurons contact and an effector cell receiving a signal. The synapse consists of two membranes - presynaptic and postsynaptic, and also from a synaptic cleft. Transmission of a nerve impulse is carried out by means of a mediator, that is, a transmitter substance. This occurs as a result of the interaction of the receptor and the mediator on the postsynaptic membrane. This is the main function of the cholinergic synapse.

Mediator and receptors

In the parasympathetic NA, the mediator is acetylcholine, the receptors are the cholinergic receptors of two types: H (nicotine) and M (muscarin). M-holinomimetiki, having a direct type of action, can stimulate receptors on the membrane of the postsynaptic type.

Synthesis of acetylcholine is carried out in the cytoplasm of neuronal cholinergic endings. It is formed from choline, as well as acetylcoenzyme-A, which has a mitochondrial origin. Synthesis occurs under the action of the cytoplasmic enzyme cholineacetylase. In synaptic vesicles, the deposition of acetylcholine occurs. In each of these bubbles may be up to several thousand acetylcholine molecules. The nervous impulse provokes the release of acetylcholine molecules into the synaptic cleft. After that he interacts with cholinergic receptors. The structure of the cholinergic synapse is unique.

Structure

According to the data available to biochemists, the neuromuscular synapse cholinergic receptor may include 5 protein subunits that surround the ion channel and pass through the entire thickness of the membrane consisting of lipids. A pair of acetylcholine molecules interacts with a pair of α-subunits. This leads to the fact that the ion channel opens and the postsynaptic membrane depolarizes.

Types of cholinergic synapses

Holinoretseptory differently localized and just as differently sensitive to the effects of pharmacological substances. In accordance with this distinguish:

• Mascarine-sensitive cholinergic receptors - the so-called M-holinoretseptory. Muscarine is an alkaloid, inherent in a number of poisonous fungi, for example, fly agarics.
• Nicotine-sensitive cholinergic receptors are the so-called H-cholinergic receptors. Nicotine is an alkaloid contained in the leaves of tobacco.

Their location

The former are located in the postsynaptic membrane of cells in the effector organs. They are located at the end of postganglionic parasympathetic fibers. In addition, they also exist in neural cells of vegetative ganglia and in the cerebral cortex. It has been established that M-cholinergic receptors of different localization are heterogeneous, which causes different sensitivity of cholinergic synapses to substances of pharmacological nature.

Kinds depending on location

Biochemists distinguish several types of M-cholinergic receptors:

• Located in the autonomic ganglia and in the central nervous system. A feature of the first is that they are localized outside the synapses - M1-holinoretseptory.
• Located in the heart. Some of them contribute to reducing the release of acetylcholine - M2-cholinergic receptors.
• Located in the smooth muscles and in most of the endocrine glands - M3-holinoretseptory.
• Located in the heart, in the walls of the pulmonary alveoli, in the central nervous system - M4-holinoretseptory.
• Located in the central nervous system, in the iris of the eye, in the salivary glands, in mononuclear blood cells - M5-holinoretseptory.

Effects on cholinergic receptors

Most of the effects of known pharmacological substances that affect M-cholinergic receptors are related to the interaction of these substances and postsynaptic M2 and M3 cholinergic receptors.

Consider the classification of funds that stimulate cholinergic synapses, below.

H-cholinergic receptors are located in the postsynaptic membrane of the ganglion neurons at the endings of each of the preganglionic fibers (in the parasympathetic and sympathetic ganglia), in the sino-carotid zone, in the adrenal medulla, in the neurohypophysis, in the Renshaw cells, in the skeletal muscles. The sensitivity of various H-cholinergic receptors is not the same as for substances. For example, H-cholinergic receptors in the structure of autonomic ganglia (neutral receptors) have significant differences from the N-cholinoreceptors in skeletal muscles (muscle type receptors). It is this special feature that allows selective blocking of ganglia with special substances. For example, kurarepodnye substances are able to block neuromuscular transmission.

Presynaptic cholinergic receptors and adrenoreceptors are involved in the regulation of the release of acetylcholine in synapses of neuro-efficient nature. Excitation of these receptors will inhibit the release of acetylcholine.

Acetylcholine interacts with H-cholinergic receptors and changes their conformation, increases the permeability level of the postsynaptic membrane. Acetylcholine exerts an exciting effect on sodium ions, which then penetrate into the cell, and this leads to the fact that the postsynaptic membrane depolarizes. Initially, a local synaptic potential arises that reaches a certain value and begins the process of generating the action potential. After this, the local excitement, which is limited by the synaptic region, begins to spread throughout the cell membrane. If M-holinoretseptor is stimulated, secondary messengers and G-proteins play a significant role in signal transmission.

Acetylcholine acts for a very short time. This is due to the fact that it is rapidly hydrolyzed by the enzyme acetylcholinesterase. Choline, which is formed during the hydrolysis of acetylcholine, will be captured in half the volume by presynaptic endings and transported to the cytoplasm of the cell for the subsequent biosynthesis of acetylcholine.

Substances that affect the cholinergic synapses

Pharmacological and diverse chemicals are capable of affecting many processes that are associated with synaptic transmission:

• The synthesis of acetylcholine.
• The process of releasing the mediator. For example, carbachol is able to enhance the process of isolation of acetylcholine, and botulinum toxin can interfere with the release of the mediator.
• The process of interaction between acetylcholine and cholinergic receptor.
• Hydrolysis of acetylcholine enzymatic nature.
• The process of capture of choline, formed as a result of hydrolysis of acetylcholine, presynaptic endings. For example, hemicholinium is able to inhibit neuronal capture and transport of choline into the cytoplasm of the cell.

Classification

The drugs that stimulate cholinergic synapses are able to exert not only this effect, but also cholinoblocking (oppressive) effect. As a basis for the classification of such substances, biochemists use the directivity of these substances to various cholinergic receptors. If we adhere to this principle, then substances that affect cholinergic receptors can be classified as follows:

• Substances that have an effect on M-holinoretseptory and H-holinoretseptory: cholinomimetics include acetylcholine and carbacholin, and holinoblokatoram - cyclodol.
• Means of anticholinesterase. These include physostigmine salicylate, proserine, galanthamine hydrobromide, armin.
• Substances that affect the cholinergic synapses. Cholinomimetics include pilocarpine hydrochloride and acetylidine, cholinoblockers - atropine sulfate, matatsin, platifillin hydrotartrate, ipratropium bromide, scopalamine hydrobromide.

• Substances that exert an influence on the H-holinoretseptory. Cholinomimetics include cititone and lobeline hydrochloride. The blockers of N-cholinergic receptors can be divided into two groups. The first - means ganglioblokiruyuschego nature. These include benzohexonium, hygronium, pentamine, arfonade, pyrilene. The second group is a mixture of curare-like substances. These include muscle relaxants that have a peripheral effect, for example, tubocurarin chloride, pancuronium bromide, pipecuronium bromide.

We examined in detail the means that affect the cholinergic synapses.