 Keywords: a nerve, a synapse, a mediator, a neuromediator, a neurotransmitter, chemistry, transfer, a pulse, a nervous tissue, sinaps blisters, neuropeptids, Acetylcholinum, Noradrenalinum, an action potential, chemical transfer of nervous impulseCHEMICAL TRANSFER OF NERVOUS IMPULSEINTRODUCTIONThe problem of transfer of the information in an organism, in particular in nervous system, is one of key questions of neurobiology and medicine. This theme is actual on a boundary of two millenia, therefore not casually the Nobel Prize in range of medicine for 2000 has got to scientists who have brought in the big contribution to research of the given range. Transfer of a pulse to nervous system descends in some stages:
From the physiological and biochemical point of view the second stage is the most complex. He represents a chain of processes which essence is reduced to transformation of an electrical signal in chemical, and then - chemical in electrical. THE HISTORY AND METHODS OF STUDYINGStudying chemical transfer to a CNS began in the beginning of XX blepharon. The data on peripheric nervous system to receive it was easy enough. Any organ it is possible to isolate, stimulate his nervous device, to collect and analyze a venous blood or a perfusate. In a CNS absolutely other position: the mass of fibers and the neurones "packed" by glial cells, which blood supply precisely to establish it is impossible, and also the "centers" having many of various inputs and localized by variously different physiologists and anatomists. By the routine methods becoming almost classical, it has been shown, that in a CNS there is Acetylcholinum, catecholamins and cholinesterases. This laborious work has enabled to draw some kind of a chemical card of a brain. Acetylcholinum is found out almost everywhere, but in especial significant amounts he contains in a bark of a brain; with the help of very specific and responsive tests have found presence of an acetylcholinesterase at some synapses, but have shown also, that it is not enough of it in others. In many centers Noradrenalinum has been found, but his immediate precursor - Dofaminum has been found in significant amounts only in fixed ranges. In various centers the serotonin has been identified also. The neuronic theory developed Ramon-i-Kahalom, the well-known Spanish histologist, is confirmed is biochemical. The neurone, his axon and the terminals synthesize a mediator which is stored in the special blisters seen with the help of a supermicroscope. These blisters, under influence of the nervous impulse coming in nerve termination, are lacerated and give vent to the contents in a synaptic gap. Blisters are formed in a neurocyton, filled by moleculas of a mediator and transported along an axon to nerve termination. Chemical messengers during transfer of nervous impulse are biologically the active materials excreted with nerve terminations. These materials refer to neuromediators (a synonym - a neurotransmitter). For short it is possible to use the term mediators. Mediators have been open by Austrian scientist Lyovi in result enough simple experience. In a normal saline solution he has placed two isolated heart of frogs and has connected them among themselves a fine tubule. Solution Ringera, perfusing in one heart, passed in the second. At a boring of a sympathetic nerve of the first heart, the second also started to be pruned. There was a hypothesis that the boring of nerves involves appearance in a perfusate of some materials which have an effect on other heart similar to effect of a boring of a sympathetic nerve. All over again the epinephrine and Acetylcholinum have been open. Now it is open more than 30 mediators, among which Noradrenalinum, a serotonin, melatonin, Histaminum, Dofaminum, oktopamin, ATF, GAMK, glycine, a glutamate, aspartat, endorphins, enkephalins, Vasopressinum, Oxytocinum, material P. On chemical composition and the mechanism of action mediators are similar to Hormonums. More in detail mediators will be considered below. Neurones have the biochemical device, the general with all other living cells, including ability to generate chemical energy by oxidation of alimentiry materials, and also to recover and conserve the integrity. Neurones have except for that specific properties which are deprived other cells and which are connected with special function of neurones as transmitters of nervous impulses: necessity for maintenance of ionic gradients that demands the big energy consumption, and the properties connected to ability of neurones to effect and excrete a panel of chemical transmitters - neuromediators. In synapses - microscopical fields where the terminal of one neurone and an accepting surface of another intimately adjoin, arrival of a pulse invokes subitaneous abjection of moleculas of a mediator from the terminal. Then these moleculas diffuse through the cleft filled with fluid between two cells and attack specific receptors of a synaptic membrane, variating thus electrical activity of an accepting neurone. For last years appreciable successes in knowledge of various mediator materials, in drawing up of cards, their allocation on a brain and in finding-out of molecular processes of sinaps transfer are achieved. By such researches it fixed, that action of many medicinal materials and neurotoxins on behaviour is based on their ability to stop or modify chemical transfer from a neurone to a neurone. In them there are also indicatings that the causes of mental diseases, probably, appear finally infringements of function of specific mediator systems of a brain. The procedure of research of a function chemistry of a brain is very complex, as mediators contain in is insignificant trace amounts, the tissue of a brain structurally and is chemically very complex and to secure for research fixed mediator frame uneasily. One of procedures have developed V.Uittejker (V. Whittaker) and Ý. de Robertis (E. de Robertis). At cautious destruction of a tissue of a brain by homogenization in solution of a saccharose many nerve terminations come off the axons and form the special selfcontained particles named "synaptosomes". Synaptosomes contain mechanisms of synthesis, storage, release and the inactivations of a mediator connected to nerve termination; a centrifugation it is possible to clear of other components of a neurone. This procedure has enabled biochemists to study mechanisms of sinaps transfer in the tube. These procedures have shown, that mediators, are posed not diffusely on all tissue of a brain, and extremely locally in circumscribed centers and pathes - cards for many mediators are made. For example, many cells of a brain keeping Noradrenalinum are concentrated in a fulcrum and form a clump known as locus coeruleus. Axons of these neurones branch strongly and projected in various ranges - a hypothalamus, a cerebellum and a neoncephalon. Noradrenalinovye neurones are involved in maintenance of a wakefulness, to system encouragements (pleasure centers), to dreamings and to a regulation of mood. The neurones keeping a monoamine Dofaminum are concentrated in substantia nigra and in ventral a tire cover. The neurones keeping Dofaminum send the axons in a neoncephalon (emotions) and in range of a striate body (a regulation of complex locomotions). The degradation dofaminovyh fibers in the given part of a brain results in a muscle tension and a tremor, signs, characteristic for illness Parkinsona. Excess of Dofaminum in limbic system of a neoncephalon, is probably involved in a schizophrenia. PROCESS OF CHEMICAL TRANSFERBiochemists have studied not only a molecular structure and anatomical allocation of different mediators, but also have reached the big successes in comprehension of exact sequence of the biochemical phenomena participating in sinaps transfer.Process of chemical transfer passes series of stages: synthesis of a mediator, his accumulation, release, interaction with a receptor and cancellation of a mediator.Each of these stages is in details characterized, and drugs which selectively enhance are found or quench a concrete stage. These researches have allowed to penetrate into the mechanism of action of psychotropic pharmaceuticals, and also to reveal connection of some nervous and mental diseases with specific infringements of sinaps mechanisms:
there Are various mechanisms of the reception on molecular level.
SYNAPSESThe term "synapse" from the Greek tongue where he means bond. Any interaction between 2 nervous cells has 3 amounting. One of them - cell or its process which send signals, - a presynaptic component. Another - a cell or its process which accepts - a postsinaps component. And the third - the messenger between the first. Phylums of synapses.Synapses on a typical neurone in a main brain are either excitant or brake, in dependence on type of a mediator discharging in them. They differ morfologicheski under a supermicroscope: for excitant synapses orbicular blisters and a continuous thickening of a synaptic membrane (1-st phylum), and for brake - impressed blisters and not continuous thickening of a membrane (2-nd phylum) are characteristic. Synapses can be categorized also on their locating on a surface of an accepting neurone - on a body of a cell, on a fulcrum or "shipike" a dendrite, or on an axon. The concept a synapse has been injected at the end of XIX blepharon by C.Sherringtonom who perceived frame which realizes transfer of a signal from the terminal of an axon of a nervous cell to effector - to a neurone, this term to a muscle fiber, a secretory cell. In dependence on a mean of transfer excrete chemical, electrical and blended synapses. In electrical synapses PD of presynaptic nerves provides depolarization of a synaptic membrane. A morphological basis of electrical transfer compounds vysokoprovodjashchy ("nizkoomnyj") fissured contact, for which are characteristic close contact pre-and postsinaps membranes (width of a synaptic gap of 2-4 nanometers), the big area of contact of these membranes, presence of the metastructures reducing electrical resistance in range of contact. For electrical sinaps transfer are characteristic:
Electrical synapses at invertebrates and the lowest backboned most wide-spread. Electrical synapses are between nervous cells, same on frame and functions. In a chemical synapse nervous impulse invokes remission from presynaptic nerves of the chemical messenger - a neuromediator which diffuses through a synaptic gap (width in 10-50 nanometers) and enters interaction with proteins - receptors of a synaptic membrane therefore the postsynaptic potential is generated. Chemical synapses are prevailing at mammalian. For chemical transfer are characteristic:
Classification: brake and excitant; akso-somatic, akso-dendritic …; cholinergic, adrenergic, purinergicheskie, peptidergicheskie, etc. There are 2 types of chemical synapses:
Sinaps blisters. Release of a mediator.Researches on nervimuscular bond have allowed Nobel winner B.Kattsu to frame the quantum theory of sinaps transfer according to which process of remission of a neuromediator develops of separate elementary reactions in 50th years of XX century, each of which represents a yield of one portion ("quantum") of a neuromediator. The neuromediator is stored in the sinaps blisters surrounded with a membrane by depth of 4-5 nanometers. The volume of blisters is approximately identical, their diameter changes from 40 up to 200 nanometers. In an axoplasm blisters are distributed irregularly and concentrated at thickenings of a presynaptic membrane acting as an axoplasm. These thickenings are awake regions, in them there is a coalescence of blisters to a presynaptic membrane and release in a synaptic gap. Release of mediators is invoked by depolarization of a presynaptic membrane with the subsequent discovering calcium channels … Sinaps blisters carry out two important functions - storage of a mediator and his release. Their life cycle can be divided into 4 stages: a biogenesis, a maturing, an exocytosis - endotsitoz and a degradation. The biogenesis will consist of 2 stages - formations in a soma of a neurone of empty sinaps blisters and aksonnogo transport of these membranous formations in the presynaptic terminal. Integrated membranous proteins are formed in AGES and further enter in device Goldzhi. Membranous formations are referred to the presynaptic terminal by means of system fast aksonnogo transport, with participation of proteins of microtubules - kinezinov. The maturing of sinaps blisters descends in the presynaptic terminal and includes 2 processes: filling of a blister by a mediator and his affixion to tsitoskeletu. In filling a blister participate: the electrogenic proton pompe creating a gradient, ion channels (for Na+, K+and Cl-), transmitting agents of electrons and specific proteins - transmitting agents of mediators. Also for a maturing of sinaps blisters their affixion to aktinovym is necessary for strands tsitoskeleta and to each other, that carries out sinapsin I, protein, coherent with a surface of a blister. The exocytosis is provided with three consecutive reactions:
During an exocytosis proteins of a membrane of a sinaps blister are involved: sinaptobrevin (VAMP), sinaptotagmin (p65), superficial protein rab3, regulating joining and cohesion and having properties GTF-ELEMENTS, sinaptofizin, forming a transmembrane pore (probably). Also participate in an exocytosis and proteins of a presynaptic membrane. It sintaksiny (HPC-1) 1 A and 1Â, capable to interreact with sinaptotagminom blisters, protein GAP-3 (nejromodulin) - a regulator of a secretion and SNAP-25, determining specificity of movings of a blister. During an exocytosis, probably, the complex of the above-stated proteins all over again is formed, and then there are the conformational changes of proteins promoting coalescence of membranes. It is formed it is time, through which contents of a blister enter in a synaptic gap. An exocytosis follows endotsitoz sinaps blisters. It is supposed, that it descends by embedding a membrane of a blister in a presynaptic membrane to the subsequent otpochkovyvaniem a membranous stuff in cytoplasm and formation so-called zonated (coated klatrinom) blisters. After the some (while unknown person) amounts of cycles of an exocytosis - endotsitoza membranous components of sinaps blisters are exposed to a degradation. Integrated proteins all over again are reverted in a neurocyton in result retrogradnogo aksonnogo transport, and superficial proteins (sinapsin I) are metabolized in nerve termination. Finding-out of stages of sinaps transfer has thrown light on a mean of action of psychotropic drugs. Some from them react, either enhancing, or relaxing release of the given mediator from aksonnyh the terminals. For example, under action of a strong stimulator of an amphetamine in a brain from nerve termination Dofaminum - a mediator connected to systems of a wakefulness and pleasure is excreted. Excessive application of an amphetamine results in distresses of intellection, a hallucination and a mania of prosecution, i.e. to the signs, similar to what are observed at some forms of a schizophrenia. Hence, there is an assumption that in a basis of signs of a schizophrenia, the superactivity dofaminovyh systems of a brain probably lays. Many psychotropic drugs react at a level of postsinaps receptors, imitating natural mediators. For example, many hallucinogens are similar on the frame to true mediators: the mescaline is similar to Noradrenalinum and Dofaminum (benzene ring), and LSD and psilotsibin are similar to a serotonin (indolnoe the ring). MEDIATORSThe neuromediator (a neurotransmitter, nejroperedatchik) is a material which is synthesized in a neurone, contains in presynaptic nerves, is liberated in a synaptic gap in reply to nervous impulse, and reacts on express fields of a postsinaps cell, causing changes a membrane potential and a metabolism of a cell. There are 4 types of mediators:
Classical mediators and their postsinaps action.ACETYLCHOLINUM.The basic localization: a medial nucleus of a septum, a diagonal sheaf, basal gigantokletochnoe a nucleus. Axons of these neurones are projected on a hippocampus, passing through a bark of the big hemispheres. Cholinergic systems participate in such functions as memory, a regulation of locomotion, a level of a wakefulness (a reticular formation of a brainstem, basal ganglions). In a spinal cord Acetylcholinum is a neuromediator in the synapses formed by a-motoneurons on cells Renshou. In vegetative nervous system AH - a mediator in all a parasympatic department and in preganglionic nerve terminations of a sympathetic department. NORADRENALINUM.Alongside with an epinephrine and Dofaminum falls into to catecholamins. Localization: in the bridge (a blue stain, lateralnaja a reticular formation of the bridge), in myelencephalon and a nucleus of a single path. Numerous (some hundreds) neurones of a blue stain form diffuse projections of the big extent, reaching practically all departments of a CNS - a bark of the big hemispheres, limbic system, a thalamus, a hypothalamus, a spinal cord. In a CNS, as a rule, - a brake mediator (bark), less often - excitant (hypothalamus). Is a mediator in all postganglionic sympathetic terminals, except for sudoriferous Ferri lactases. THE EPINEPHRINE.At mammalian few adrenalinic pathes. An epinephrine sekretiruetsja it is diffuse (in a medulla of paranephroses) and carries out, first of all, a role of Hormonum. DOFAMINUM.It is localized on the average a brain (a black substance, a ventral tire cover), an olfactory bulb, a hypothalamus and periventrikuljarnoj ranges of myelencephalon. THE SEROTONIN.Localization: nucleus of a juncture in a rostral part of the bridge, these neurones yield projections to limbic system, basal ganglions, a bark of the big hemispheres. 5-ÍÒ (5-ãèäðîêñèòðèïòàìèí) plays the important role in a regulation of an affective behavior, a motor performance, a feeding behavior, dream, a thermoregulation, participates in the control of neuroendocrinal systems. L-GLUTAMIC.Is the main excitant mediator, it is localized in all departments of a CNS. THE ASPARTIC ACID.An excitant mediator on the average a brain, and in a forward and back pole of a spinal cord. GAMK.The g-aminobutyric acid (GAMK) which is not included in proteins concerns to routine brake mediators of a brain. GAMK it is developed exclusively in a main and spinal brain. Not less than thirds (up to 50 %) synapses of a brain use as mediator GAMK. For example, for chorea Gentingtona - ancestral neurologic disease specific deficiency GAMK in a brain is characteristic. Consensual locomotions arising at it with gradual destruction of a striate body coming in the middle age. Postmortem researches have shown, that in a basis of illness deficiency GAMK lays. GLYCINE.In a spinal cord realizes postsinaps inhibitions of activity of motoneurons, being liberated from the terminals of cells Renshou. Also is a neuromediator in brake internejronah a diencephalon and a reticular formation. ATF.Is a mediator in all synapses formed by a metasympathetic department of vegetative nervous system on unstriated muscles. Action ATF thus is realized by the purine receptors conjugate to calcium ion channels. The adenosine plays a role nejromoduljatora through metabotropnye receptors. Renders mainly brake influence on series of excitant synapses. NEJROMODULJATORY, KOMEDIATORY, NEUROPEPTIDSNejromoduljatoryExist "nejromoduljatory", not having self-contained physiological action, and modifying effect of neuromediators. Action nejromoduljatorov has tonic character - sluggish development and the big duration of action. A parentage - not necessarily neuronic, for example, the glia can synthesize series nejromoduljatorov. Action is not initiated by nervous impulse and not always conjugate to effect of a mediator. Targets: not only receptors on a synaptic membrane, and different fields of a neurone, including endocellular. There are 2 kinds nejromoduljatsii:
KomediatoryConcomitant (coexisting) mediators (komediatory, kotransmittery) are the sinaps messengers described first of all by collateral localization, collateral release and the general cell - target. Collateral localization is perceived as synthesis and a deposition of mediators in the same neurone, their parentage in the same presynaptic nerves, but it is not necessary in the same blisters. Collateral release is perceived as an exocytosis of two (and more) mediators, as a result of the same activation of the presynaptic terminal which in this case is meant not as a single presynaptic action potential, and the discharge of action potentials with the same frequency. NeuropeptidsFor last years after in a brain the new class of chemical combinations - neuropeptids has been found, the number of known systems of chemical messengers in a brain has sharply increased. Neuropeptids represent chains of aminoacidic oddments (2-39). Many of them are localized in aksonnyh the terminals. Neuropeptids differ from earlier identified mediators that they organize such complex phenomena as memory, thirst, a sexual behavior, etc. For example, the somatostatin depresses abjection of a growth hormone by a pituitary body, controls a secretion of an insulin and a glucagon a pancreas and functions as a mediator in spinal and a brain. PRINCIPLES OF TRANSFER AND THEIR MODERN ADDITIONSPrinciple Dejla.According to the law (principle) formulated in 30th years Dejla, the material identified as a mediator in one synapse, should be a mediator and in all other synapses formed by the same neurone. It was found out later, that in one neurone it can be synthesized more than 1 mediator material, that each presynaptic terminal can liberate more than one mediator (neuropeptids, komediatory, nejromoduljatory), however the panel of mediators for fixed type of neurones is constant. Principle EkklsaThe mediator, discharged nerve termination of a fixed neurone, always renders on the same synaptic membrane identical action - either exaltation, or the inhibition connected to the same ionic mechanism. However it is not absolutely true. The modern principle of multiplicity of a mediator signal means the following: character of sinaps action is determined not by the chemical nature of a mediator, and the nature of receptors of a postsinaps cell, i.e. the same mediator can render various action. That is the same mediator can render either excitant or inhibiting action in dependence on a receptor. One postsinaps cell can have more than 1 type of receptors for the given mediator and each of these receptors is capable to supervise the different mechanism of ion permeability. Volumetric transferNow these classical representations about chemical signaling in nervous system essentially are added. Not so long ago nervimuscular bond was considered as a typical chemical synapse, morfofunktsionalnaja which organization provides fast transfer of a signal to " the anatomical address ". In nervous system frequently it is possible to find systems in which transfer descends to " the chemical address ", i.e. it spetsializirovannost it is determined not by morphological contact pre-and postsinaps frames, and that circumstance, that express receptors are only on cells - targets. Last years in the literature there are many acknowledgement, that intermediator interaction in a CNS is in part realized by not sinaps way. New nejrotransmitternyj the mechanism has received the name of volumetric transfer. He is based on a sluggish diffusion of neuromediators on intercellular space and their action on remote from a place of outlier not sinaps receptors. For example, in the organs incorporating a sleek muscle tissue mezenhimnogo of type, terminali nerve fibrils come to an end not immediately on myocytes, and between them. And after entering nervous impulse, the mediator propagates diffusely, provoking at once many cells. Such mechanism is carried out in walls of blood vessels, a tubular internals, and also in separate shallow muscles (tsiliarnyh). And release of neuropeptids rather frequently descends far from a cell - target. the List of the literature
To discuss a material at a forum of a site Keywords: a nerve, a synapse, a mediator, a neuromediator, a neurotransmitter, chemistry, transfer, a pulse, a nervous tissue, sinaps blisters, neuropeptids, Acetylcholinum, Noradrenalinum, an action potential, chemical transfer of nervous impulse Main | Abstracts, compositions, lectures | Psychiatry | Links
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