Cholinergic synapses: structure, functions

Cholinergic synapses are a place in which two neurons or neurons contact and an effector cell receiving a signal. Synapse consists of two membranes - presynaptic and postsynaptic, and also from a synaptic cleft. Transmission of the 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 NC, the mediator is acetylcholine, the receptors are the cholinoreceptors 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 of

According to the data available to biochemists, the neuromuscular synapse cholinergic receptor 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 depolarizes.

Types of cholinergic synapses

Holinoretseptory differently localized and also 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 first are located in the postsynaptic cell membrane 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.

Species depending on the location of the

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-cholinoreceptors.
• Located in the smooth muscles and in most of the endocrine glands are M3-cholinoreceptors.
• 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.

Effect on cholinergic receptors

Most of the effects of known pharmacological agents 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.

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 type receptors) differ significantly from H-cholinergic receptors in skeletal muscles( muscle type receptors).It is this particular feature that allows selective blocking of ganglia with special substances. For example, kurarepodnye substances are capable of blocking neuromuscular transmission.

Presynaptic cholinergic receptors and adrenergic receptors participate in the regulation of the release of acetylcholine in synapses of a neuro-efficient nature. The excitation of these receptors will inhibit the release of acetylcholine.

Acetylcholine interacts with H-cholinergic receptors and changes their conformation, increases the permeability 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 stimulation of the M-holinoretseptor occurs, then in the signal transmission a significant role is played by the secondary messengers and G-proteins.

Acetylcholine is effective 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 process of synthesis of acetylcholine.
• The mediator release process. 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, with presynaptic endings. For example, hemicholinium is able to inhibit neuronal capture and transport of choline into the cytoplasm of the cell.

Classification of

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

• Substances that affect M-cholinergic receptors and H-cholinergic receptors: cholinomimetics include acetylcholine and carbacholin, and holinoblockers are cyclodol.
• Anticholinesterase agents. 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 exerting influence on the H-cholinergic receptors. 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, tubocurarine chloride, pancuronium bromide, pipecuronium bromide.

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