Cholinergic synapses are the place where two neurons, or a neuron and an effector cell that receives a signal, come into contact. The synapse consists of two membranes - the presynaptic and postsynaptic, as well as the synaptic cleft. The transmission of a nerve impulse is carried out through a mediator, that is, a transmitter substance. This happens 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 NS, the mediator is acetylcholine, the receptors are cholinergic receptors of two types: H (nicotine) and M (muscarine). M-cholinomimetics, which have a direct type of action, can stimulate receptors on the membrane of the postsynaptic type.
The synthesis of acetylcholine is carried out in the cytoplasm of neuronal cholinergic endings. It is formed from choline, as well as acetyl coenzyme-A, which has a mitochondrialorigin. Synthesis occurs under the action of the cytoplasmic enzyme choline acetylase. Acetylcholine is deposited in synaptic vesicles. Each of these vesicles can contain up to several thousand acetylcholine molecules. The nerve impulse provokes the release of acetylcholine molecules into the synaptic cleft. After that, it interacts with cholinergic receptors. The structure of the cholinergic synapse is unique.
Building
According to the data that biochemists have, the cholinergic receptor of the neuromuscular synapse can include 5 protein subunits that surround the ion channel and pass through the entire thickness of the membrane, which consists of lipids. A pair of acetylcholine molecules interacts with a pair of α-subunits. This causes the ion channel to open and the postsynaptic membrane to depolarize.
Types of cholinergic synapses
Cholinoreceptors are differently localized and also differently sensitive to the effects of pharmacological substances. In accordance with this, they distinguish:
- Mascarin-sensitive cholinergic receptors - the so-called M-cholinergic receptors. Muscarine is an alkaloid found in a number of poisonous mushrooms such as fly agaric.
- Nicotine-sensitive cholinergic receptors - the so-called H-cholinergic receptors. Nicotine is an alkaloid found in tobacco leaves.
Their location
The first are located in the postsynaptic membrane of cells as part of the effector organs. They are located at the endpostganglionic parasympathetic fibers. In addition, they are also found in the neuronal cells of the autonomic 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 a pharmacological nature.
Views depending on location
Biochemists distinguish between several types of M-cholinergic receptors:
- Located in the autonomic ganglia and in the central nervous system. The peculiarity of the former is that they are localized outside the synapses - M1-cholinergic receptors.
- Located in the heart. Some of them help to reduce the release of acetylcholine - M2-cholinergic receptors.
- Located in smooth muscles and in most of the endocrine glands - M3-cholinergic receptors.
- Located in the heart, in the walls of the pulmonary alveoli, in the central nervous system - M4-cholinergic receptors.
- Located in the central nervous system, in the iris of the eye, in the salivary glands, in mononuclear blood cells - M5-cholinergic receptors.
Influence on cholinergic receptors
Most of the effects of known pharmacological substances that affect M-cholinergic receptors are associated with the interaction of these substances and postsynaptic M2- and M3-cholinergic receptors.
Let's consider the classification of drugs that stimulate cholinergic synapses below.
H-cholinergic receptors are located in the postsynaptic membrane of ganglion neurons at the ends of each of the preganglionic fibers (in parasympathetic and sympatheticganglia), in the carotid sinus zone, in the adrenal medulla, in the neurohypophysis, in Renshaw cells, in skeletal muscles. The sensitivity of various H-cholinergic receptors is not the same to substances. For example, H-cholinergic receptors in the structure of autonomic ganglia (neutral-type receptors) differ significantly from H-cholinergic receptors in skeletal muscles (muscle-type receptors). It is this feature of them that allows them to selectively block the ganglia with special substances. For example, curarepod substances can block neuromuscular transmission.
Presynaptic cholinergic receptors and adrenoreceptors are involved in the regulation of the release of acetylcholine in synapses of neuroeffector nature. Excitation of these receptors will inhibit the release of acetylcholine.
Acetylcholine interacts with H-cholinergic receptors and changes their conformation, increases the level of postsynaptic membrane permeability. Acetylcholine has an excitatory 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, which reaches a certain value and begins the process of generating an action potential. After that, local excitation, which is limited to the synaptic region, begins to spread throughout the entire cell membrane. If M-cholinergic receptor stimulation occurs, then secondary messengers and G-proteins play a significant role in signal transmission.
Acetylcholine workswithin a very short time. This is due to the fact that it is rapidly hydrolyzed by the action of the enzyme acetylcholinesterase. Choline, which is formed during the hydrolysis of acetylcholine, will be captured by presynaptic endings in half the volume and transported to the cytoplasm of the cell for subsequent biosynthesis of acetylcholine.
Substances that act on cholinergic synapses
Pharmacological and a variety of chemicals can affect many processes that are associated with synaptic transmission:
- The process of synthesis of acetylcholine.
- The mediator release process. For example, carbacholin can enhance the release of acetylcholine, and botulinum toxin can interfere with the release of the neurotransmitter.
- The process of interaction between acetylcholine and the cholinergic receptor.
- Hydrolysis of acetylcholine of enzymatic nature.
- The process of capturing choline, formed as a result of the hydrolysis of acetylcholine, by presynaptic endings. For example, hemicholinium is able to inhibit neuronal uptake and transport of choline into the cell cytoplasm.
Classification
Means that stimulate cholinergic synapses can have not only this effect, but also anticholinergic (depressant) effect. As a basis for the classification of such substances, biochemists use the direction of action of these substances on various cholinergic receptors. If aadhere to this principle, then substances that affect cholinergic receptors can be classified as follows:
- Substances that affect M-cholinergic receptors and H-cholinergic receptors: cholinomimetics include acetylcholine and carbachol, and anticholinergics - cyclodol.
- Means of anticholinesterase character. These include physostigmine salicylate, prozerin, galanthamine hydrobromide, armine.
- Substances that affect cholinergic synapses. Cholinomimetics include pilocarpine hydrochloride and aceclidine, anticholinergics include atropine sulfate, matatsin, platyfillin hydrotartrate, ipratropium bromide, scopalamine hydrobromide.
- Substances that affect H-cholinergic receptors. Cholinomimetics include cytiton and lobelin hydrochloride. N-cholinergic blockers can be divided into two groups. The first is ganglion-blocking agents. These include benzohexonium, gigronium, pentamin, arfonad, pyrilene. The second group includes curare-like substances. These include peripheral muscle relaxants such as tubocurarine chloride, pancuronium bromide, pipecuronium bromide.
We looked in detail at the drugs that affect cholinergic synapses.
