Cholinergic synapses are the place where the contact of two neurons or a neuron and an effector cell receiving a signal occurs. 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 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 a parasympathetic NS, acetylcholine is a mediator, and two types of cholinergic receptors are receptors: H (nicotine) and M (muscarine). M-cholinomimetics with a direct type of action can stimulate receptors on the postsynaptic type membrane.
Acetylcholine synthesis is carried out in the cytoplasm of neural cholinergic endings. It is formed from choline, as well as acetyl coenzyme-A, which is of mitochondrial origin. The synthesis occurs under the action of the cytoplasmic enzyme cholinacetylase. In synaptic vesicles, acetylcholine is deposited. Each of these vesicles can contain up to several thousand acetylcholine molecules. A 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.
Structure
According to the data available to biochemists, 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 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 is depolarized.
Types of cholinergic synapses
Cholinergic receptors are localized differently and are also differently sensitive to the effects of pharmacological substances. In accordance with this distinguish:
- Maskarin-sensitive cholinergic receptors are the so-called M-cholinergic receptors. Muscarine is an alkaloid inherent in a number of poisonous mushrooms, such as fly agaric.
- Nicotine-sensitive cholinergic receptors are the so-called H-cholinergic receptors. Nicotine is an alkaloid found in tobacco leaves.
Their location
The former are located in the postsynaptic membrane of cells as part of effector organs. They are located at the ends of postganglionic parasympathetic fibers. In addition, they are also found in the neural cells of the autonomic ganglia and in the cerebral cortex. It was established that M-cholinergic receptors of various localization are heterogeneous, which leads to different sensitivity of cholinergic synapses to substances of a pharmacological nature.
Views depending on location
Biochemists distinguish several types of M-cholinergic receptors:
- Located in the vegetative ganglia and in the central nervous system. A feature 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 the 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 are M4-cholinergic receptors.
- M5-cholinergic receptors located in the central nervous system, in the iris, in the salivary glands, in mononuclear blood cells.
Effects on cholinergic receptors
Most of the effects of known pharmacological substances affecting M-cholinergic receptors are associated with the interaction of these substances and postsynaptic M2- and M3-cholinergic receptors.
Consider the classification of agents that stimulate cholinergic synapses below.
N-cholinergic receptors are located in the postsynaptic membrane of ganglion neurons at the ends of each of the preganglionic fibers (in the parasympathetic and sympathetic ganglia), in the synocarotid zone, in the adrenal medulla, in the neurohypophysis, in Renshaw cells, in skeletal muscle. The sensitivity of various H-cholinergic receptors is not the same for substances. For example, N-cholinergic receptors in the structure of autonomic ganglia (neutral type receptors) have significant differences from H-cholinergic receptors in skeletal muscle (muscle type receptors). It is this feature of them that allows you to selectively block the ganglia with special substances. For example, curariform substances can block neuromuscular transmission.
Presynaptic cholinergic receptors and adrenergic receptors are involved in the regulation of the release of acetylcholine in synapses of a neuro-effector 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 permeability of the postsynaptic membrane. Acetylcholine has an exciting effect on sodium ions, which then penetrate into the cell, and this leads to the fact that the postsynaptic membrane is depolarized. Initially, a local synaptic potential arises, which reaches a certain value and begins the process of generating an action potential. After this, local excitation, which is limited to the synaptic region, begins to spread throughout the cell membrane. If stimulation of the M-cholinergic receptor occurs, then 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 rapidly hydrolyzes under the action of the enzyme acetylcholinesterase. Choline, which is formed during the hydrolysis of acetylcholine, in half the volume will be captured by presynaptic ends and transported to the cell cytoplasm for subsequent biosynthesis of acetylcholine.
Substances that affect cholinergic synapses
Pharmacological and a variety of chemicals can affect many processes that are associated with synaptic transmission:
- Acetylcholine synthesis process.
- The process of release of the mediator. For example, carbacholine can enhance the release of acetylcholine, and botulinum toxin can interfere with the release of the mediator.
- The process of interaction between acetylcholine and cholinergic receptors.
- Hydrolysis of acetylcholine of an enzymatic nature.
- The process of capturing choline formed by the hydrolysis of acetylcholine, presynaptic ends. 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 a cholinergic (inhibitory) effect. As a basis for the classification of such substances, biochemists use the directivity of the action of these substances on various cholinergic receptors. If you adhere to this principle, then substances that affect cholinergic receptors can be classified as follows:
- Substances that affect M-cholinergic receptors and H-cholinergic receptors: acetylcholine and carbacholine belong to cholinomimetics, and cyclodol belong to cholinergic antagonists.
- Anticholinesterase agents . These include physostigmine salicylate, proserin, galantamine hydrobromide, armin.
- Substances that affect cholinergic synapses. Cholinomimetics include pilocarpine hydrochloride and aceclidine, anticholinergic agents include atropine sulfate, matacin, platifillin hydrotartrate, ipratropium bromide, scopalamine hydrobromide.
- Substances affecting N-cholinergic receptors. Cholinomimetics include cytitone and lobelin hydrochloride. Blockers of H-cholinergic receptors can be divided into two groups. The first is ganglion blocking agents. These include benzohexonium, hygronium, pentamine, arfonad, pyrene. The second group eats curariform substances. These include muscle relaxants that have a peripheral effect, for example tubocurarine chloride, pancuronium bromide, pipecuronium bromide.
We examined in detail the drugs that affect cholinergic synapses.