Cell membranes

Image of a cell membrane. Small blue and white balls correspond to the hydrophilic "heads" of lipids, and the lines attached to them correspond to the hydrophobic "tails". The figure shows only integral membrane proteins (red globules and yellow helices). Yellow oval dots inside the membrane - cholesterol molecules Yellow-green chains of beads on the outside of the membrane - oligosaccharide chains that form the glycocalyx

The biological membrane also includes various proteins: integral (penetrating the membrane through), semi-integral (immersed at one end into the outer or inner lipid layer), surface (located on the outer or adjacent to the inner sides of the membrane). Some proteins are the points of contact of the cell membrane with the cytoskeleton inside the cell, and the cell wall (if any) outside. Some of the integral proteins function as ion channels, various transporters, and receptors.

Functions of biomembranes

barrier - provides a regulated, selective, passive and active metabolism with the environment. For example, the peroxisome membrane protects the cytoplasm from peroxides dangerous to the cell. Selective permeability means that the permeability of a membrane to various atoms or molecules depends on their size, electrical charge, and chemical properties. Selective permeability ensures the separation of the cell and cellular compartments from the environment and supply them with the necessary substances.

transport - through the membrane there is a transport of substances into the cell and out of the cell. Transport through membranes provides: the delivery of nutrients, the removal of end products of metabolism, the secretion of various substances, the creation of ionic gradients, the maintenance of the appropriate pH and ionic concentration in the cell, which are necessary for the operation of cellular enzymes.

Particles that for some reason are not able to cross the phospholipid bilayer (for example, due to hydrophilic properties, since the membrane inside is hydrophobic and does not allow hydrophilic substances to pass through, or because of their large size), but necessary for the cell, can penetrate the membrane through special carrier proteins (transporters) and channel proteins or by endocytosis.

In passive transport, substances cross the lipid bilayer without energy expenditure, by diffusion. A variant of this mechanism is facilitated diffusion, in which a specific molecule helps a substance to pass through the membrane. This molecule may have a channel that allows only one type of substance to pass through.

Active transport requires energy, as it occurs against a concentration gradient. There are special pump proteins on the membrane, including ATPase, which actively pumps potassium ions (K +) into the cell and pumps sodium ions (Na +) out of it.

matrix - provides a certain relative position and orientation of membrane proteins, their optimal interaction;

mechanical - ensures the autonomy of the cell, its intracellular structures, as well as connection with other cells (in tissues). Cell walls play an important role in providing mechanical function, and in animals - intercellular substance.

energy - during photosynthesis in chloroplasts and cellular respiration in mitochondria, energy transfer systems operate in their membranes, in which proteins also participate;

receptor - some proteins located in the membrane are receptors (molecules with which the cell perceives certain signals).

For example, hormones circulating in the blood only act on target cells that have receptors corresponding to those hormones. Neurotransmitters (chemicals that conduct nerve impulses) also bind to specific receptor proteins on target cells.

enzymatic - membrane proteins are often enzymes. For example, the plasma membranes of intestinal epithelial cells contain digestive enzymes.

implementation of generation and conduction of biopotentials.

With the help of the membrane, a constant concentration of ions is maintained in the cell: the concentration of the K + ion inside the cell is much higher than outside, and the concentration of Na + is much lower, which is very important, since this maintains the potential difference across the membrane and generates a nerve impulse.

cell marking - there are antigens on the membrane that act as markers - "labels" that allow the cell to be identified. These are glycoproteins (that is, proteins with branched oligosaccharide side chains attached to them) that play the role of "antennas". Due to the myriad of side chain configurations, it is possible to make a specific marker for each cell type. With the help of markers, cells can recognize other cells and act in concert with them, for example, when forming organs and tissues. It also allows the immune system to recognize foreign antigens.

Structure and composition of biomembranes

Membranes are composed of three classes of lipids: phospholipids, glycolipids, and cholesterol. Phospholipids and glycolipids (lipids with carbohydrates attached to them) consist of two long hydrophobic hydrocarbon "tails" that are associated with a charged hydrophilic "head". Cholesterol stiffens the membrane by occupying the free space between the hydrophobic lipid tails and preventing them from bending. Therefore, membranes with a low cholesterol content are more flexible, while those with a high cholesterol content are more rigid and brittle. Cholesterol also serves as a “stopper” that prevents the movement of polar molecules from and into the cell. An important part of the membrane is made up of proteins penetrating it and responsible for various properties of membranes. Their composition and orientation in different membranes differ.

Cell membranes are often asymmetric, that is, the layers differ in lipid composition, the transition of an individual molecule from one layer to another (the so-called flip flop) is difficult.

Membrane organelles

These are closed single or interconnected sections of the cytoplasm, separated from the hyaloplasm by membranes. Single-membrane organelles include endoplasmic reticulum, Golgi apparatus, lysosomes, vacuoles, peroxisomes; to two-membrane - nucleus, mitochondria, plastids. Outside, the cell is limited by the so-called plasma membrane. The structure of the membranes of various organelles differs in the composition of lipids and membrane proteins.

Selective permeability

Cell membranes have selective permeability: glucose, amino acids, fatty acids, glycerol and ions slowly diffuse through them, and the membranes themselves actively regulate this process to a certain extent - some substances pass through, while others do not. There are four main mechanisms for the entry of substances into the cell or their removal from the cell to the outside: diffusion, osmosis, active transport and exo- or endocytosis. The first two processes are passive in nature, that is, they do not require energy; the last two are active processes associated with energy consumption.

The selective permeability of the membrane during passive transport is due to special channels - integral proteins. They penetrate the membrane through and through, forming a kind of passage. The elements K, Na and Cl have their own channels. With respect to the concentration gradient, the molecules of these elements move in and out of the cell. When irritated, the sodium ion channels open, and there is a sharp influx of sodium ions into the cell. This results in an imbalance in the membrane potential. After that, the membrane potential is restored. Potassium channels are always open, through which potassium ions slowly enter the cell.

The selectivity and permeability of membranes must be considered in relation to the costs of obtaining oxygen-enriched air. Air separation costs depend on permeability, selectivity, geometric parameters of the membranes, module performance, cost of electricity and other factors. The cost of oxygen-enriched air is estimated in relation to the equivalent pure oxygen, defined as the amount of pure oxygen required to mix with air (21% oxygen) to obtain the same amount and percentage of oxygen that is obtained in the gas separation process in question.[ ...]

Ultrafiltration is a membrane process for the separation of solutions whose osmotic pressure is low. This method is used in the separation of relatively high molecular weight substances, suspended particles, colloids. Ultrafiltration compared to reverse osmosis is a more efficient process, since high membrane permeability is achieved at a pressure of 0.2-1 MPa.[ ...]

Solid waste washing 434, 425 Membrane permeability 273 Straining 197 cl.[ ...]

Calcium ions have a great influence on membrane structures. The need for Ca2+ ions to stabilize membranes has long been pointed out. It has been shown that the presence of Ca2+ ions in the surrounding solution is necessary for the formation of a surface membrane on an endoplasmic droplet isolated from interdistant cells of Chara algae. The presence of Ca2+ at a concentration of 10 4 M promoted the formation of a surface membrane on the droplet, although not strong enough; a stronger membrane was formed at a concentration of 10-3 M and especially 10 2 M. When calcium ions are removed (for example, when treated with chelates or in the absence of Ca2 + in the medium), mucilage of root hairs is noted, and the permeability of membranes to other substances also increases. Ca2 + ions change and electrical properties of both artificial and natural membranes, reducing the charge density on the membrane surface.The lack of Ca leads to an increase in vacuolization, changes in chromosomes, rupture of ER membranes and other intracellular compartments.[ ...]

With an increase in the concentration of the separated solution, the permeability of the membranes decreases, and with an increase in pressure, it increases. After the purification process, a filtrate is obtained, depleted by 90-99.5 ° / o in the original compounds, and a concentrate sent for further processing.[ ...]

The response to acetylcholine and biogenic amines is to change the permeability of membranes to ions and/or induce the synthesis of second messengers. The presence of cAMP, cGMP, Ca2+, as well as synthesis and catabolism enzymes in the plant cell and its organelles, confirms the possibility of local mediation.[ ...]

So, under the action of microwave EMR (2.45 GHz), an increase in the cation permeability of erythrocyte membranes at room temperature was found, while in the absence of microwave EMR, a similar effect is observed only at a temperature of 37 °C.[ ...]

The metabolite funds are not evenly distributed throughout the cell, but separated by membranes and localized in separate compartments (chambers, compartments). The compartments of the metabolic funds of the cell are interconnected by transport flows. In accordance with the selective permeability of membranes, a spatial redistribution of intermediates and metabolic products occurs. For example, in a cell, the supply of ATP is maintained due to the "horizontal" links between the processes of photosynthetic and oxidative phosphorus formation.[ ...]

solution concentration. With an increase in the concentration of the separated solution, the permeability of the membranes decreases due to an increase in the osmotic pressure of the solvent and the effect of concentration polarization. With a Reynolds criterion value of 2000-3000, concentration polarization is practically absent, however, turbulization of the solution is associated with its multiple recirculation, i.e., with energy costs, and leads to the accumulation of suspended particles in the solution and the appearance of biological fouling.[ ...]

A decrease in water temperature, leading to cooling of fish, also leads to an increase in the permeability of membranes, which lose their ability to maintain ionic gradients. In this case, the conjugation of enzymatic reactions is disturbed, ion pumps stop working, the work of the central and peripheral nervous systems is disrupted, the work of the cardiorespiratory apparatus is inhibited, which ultimately can lead to the development of hypoxia. When overheating or cooling of fish, resulting from a sharp change in temperature in a limited time, a certain role belongs to osmotic stress due to a violation of the body's ability to maintain a certain concentration of ions and proteins in the blood. For example, a decrease in temperature from 25 to 11 ° C causes the development of a coma in tilapia kept in fresh water, accompanied by a decrease in the concentration of sodium and chlorine ions and total blood protein. According to the authors, the death of fish occurs due to the development of osmoregulatory collapse and inhibition of kidney function. An indirect confirmation of this assumption can be the prevention of thermal coma in fish kept in dilute sea water, which is consistent with earlier observations of an increase in the thermal resistance of fish due to the addition of sodium, calcium and magnesium ions to the water. However, it should be borne in mind that the causes of fish death at elevated or low temperatures are different and depend on the duration and intensity of the temperature effect.[ ...]

pH value. A change in the initial pH usually results in a decrease in membrane permeability. The effect of pH on membrane selectivity is small. Volatile acids are poorly retained by membranes, therefore, preliminary neutralization of volatile acids increases the selectivity of the separation process.[ ...]

At high salt concentrations in a three-chamber electrodialyzer with inert membranes, the maximum current efficiency does not exceed 20%.[ ...]

Positive results have been obtained for wastewater treatment from OP-7 by reverse osmosis at a pressure of 5 MPa. Membrane permeability was 5-20.8 l/(m2-h) at a concentration of OP-7 in the filtrate of 1-18 mg/l.[ ...]

Surfactants (alkyl sulfates) stimulate the reproduction of bacteria to the greatest extent. In addition, surfactants, by changing the permeability of the membranes of living cells (S. S. Stroev, 1965, etc.), may contribute to better digestibility of nutrients contained in water by microbes.[ ...]

The nature of the solute has a certain effect on selectivity and, to a lesser extent, on membrane permeability. This influence lies in the fact that inorganic substances are retained by membranes better than organic substances with the same molecular weight; among related compounds, for example, homologues, substances with a higher molecular weight are better retained; substances that form bonds with the membrane, for example, hydrogen, are retained by the membrane the better, the less strong this bond is; the selectivity of the retention of macromolecular compounds by ultrafiltration is the greater, the greater the molecular weight of the solute.[ ...]

Cellulose acetate membranes can operate in the pH range of 4.5-7, and those made of chemically resistant polymers can operate at pH 1-14. The permeability of the membranes is chosen to allow the passage of water, soluble salts and retain oils. The pore size in membranes is usually in the range of 2.5-10 nm. The plant is equipped with auxiliary pipelines for flushing the membranes with filtrate or demineralized water, equipped with instrumentation and automatic devices.[ ...]

With a significant decrease in the intracellular potential difference to a certain threshold level, a sharp change in membrane permeability and reversal (reversion) of ion fluxes are observed. Calcium ions from the external environment surrounding the cell enter it, while chloride ions and potassium ions leave the cell into the bathing solution.[ ...]

Tolerance is associated with internal factors and includes such metabolic processes as selective uptake of ions, reduced membrane permeability, immobilization of ions in certain parts of plants, removal of ions from metabolic processes through the formation of a reserve in insoluble forms in various organs, adaptation to the replacement of a physiological element with a toxic one in enzyme, removal of ions from plants by leaching through leaves, sap, shedding leaves, excretion through roots. Tolerant plants can be stimulated at elevated concentrations of metals, which indicates their physiological need for excess. Some plant species are capable of accumulating a significant amount of heavy metals without visible signs of oppression. Other plants do not have this ability (see table[ ...]

Pressure is one of the main factors that determine the performance of reverse osmosis plants. The performance of the membranes increases with an increase in excess pressure. However, starting from a certain pressure, the permeability of the membranes decreases due to the compaction of the polymeric material of the membrane.[ ...]

It has also been established that low ([ ...]

Since hemicellulose polysaccharides have a number average molecular weight of no more than 30,000, the use of conventional osmometry is difficult due to the permeability of membranes for low molecular weight fractions. Hill's method of vapor phase osmometry has a number of advantages over other methods. This method is based on measuring the difference between the vapor pressure of a solution and a solvent and is as follows. A drop of solution and a drop of solvent are placed on two thermocouple junctions and kept in an atmosphere saturated with pure solvent vapors. Due to the reduced vapor pressure of the solution, part of the vapor will condense on the solution drop, raising the temperature of the drop and the thermocouple. The resulting electromotive force is measured with a galvanometer. The upper limit of the measured value of the molecular weight is about 20,000, the measurement accuracy is 1%.[ ...]

Finally, the membranes of the endoplasmic reticulum are the surfaces along which biocurrents propagate, which are signals that change the selective permeability of membranes and thereby the activity of enzymes. Thanks to this, some chemical reactions are set in motion, others are inhibited - the metabolism is subject to regulation and proceeds in a coordinated manner.[ ...]

The plasmalemma regulates the entry of substances into the cell and their exit from it, ensures the selective penetration of substances into and out of the cell. The rate of penetration through the membrane of different substances is different. Water and gaseous substances penetrate well through it. Fat-soluble substances also easily penetrate, probably due to the fact that it has a lipid layer. It is assumed that the lipid layer of the membrane is permeated with pores. This allows substances that are insoluble in fats to pass through the membrane. The pores carry an electrical charge, so the penetration of ions through them is not completely free. Under certain conditions, the charge of the pores changes, and this regulates the permeability of membranes for ions. However, the membrane is not equally permeable for different ions with the same charge, and for different uncharged molecules of similar sizes. This shows the most important property of the membrane - the selectivity of its permeability: for some molecules and ions, it is better permeable, for others worse.[ ...]

Currently, the mechanism of action of mediators in animal and plant cells, which is based on the regulation of ion fluxes, is generally recognized. Changes in membrane potentials are due to shifts in the ion permeability of membranes by opening or closing ion channels. This phenomenon is associated with the mechanisms of occurrence and propagation of AP in animal and plant cells. In animal cells, these are N7K+ channels controlled by acetylcholine and Ca2+ channels, more often dependent on biogenic amines. In plant cells, the occurrence and spread of AP is associated with calcium, potassium and chloride channels.[ ...]

With greater reproducibility and stability, a stable flow of gases and vapors can be obtained by methods based on the diffusion of gases or liquid vapors through a capillary (Fig. 10) or a permeable membrane (Fig. 11) into the diluent gas stream. In such methods, an equilibrium is observed between the gas phase and the adsorbing surfaces of the equipment, which ensures the stability of the microflow.[ ...]

An increase in temperature leads to a decrease in the viscosity and density of the solution and, simultaneously, to an increase in its osmotic pressure. Reducing the viscosity and density of the solution increases the permeability of membranes, and an increase in osmotic pressure reduces the driving force of the process and reduces the permeability.[ ...]

In any living system, there is a REB, and it would be surprising if it were not. This would mean absolute equality of electrolyte concentrations in all cells, organs, external solutions, or complete coincidence of membrane permeability to all cations and anions.[ ...]

In experiment 6, similar to experiment 1, the amount of released potassium and water-soluble organic matter was determined at different concentrations of atrazine. Judging by the results obtained, it can be said that atrazine does not increase the permeability of membranes for low molecular weight organic substances and increases for potassium. This effect was proportional to the concentration of atrazine.[ ...]

When examining persons exposed to low-level radiation during work (for example, radiologists and technicians working with x-rays, the doses of which were measured by individual dosimeters) using the method of labeled atoms, blood tests were performed on the permeability of erythrocyte membranes during the passage of monovalent cations. It was found that the permeability of erythrocyte membranes in irradiated individuals is significantly higher than in those who were not irradiated. In addition, the dependence plot made it possible to establish a rapid increase in permeability at low irradiation; at high doses, the curve becomes flat, similar to Stokke's observation in animal studies (see Fig. XIV-3). These data are consistent with the results obtained by Petkau.[ ...]

When desalination of saline wastewater by hyperfiltration through semi-permeable membranes, the main parameters - the concentration of dissolved substances in the concentrate and filtrate must be determined per unit width of the membrane at a given length, separating capacity, membrane permeability coefficient, pressure, flow rates of source water, filtrate and concentrate.[ .. .]

The possibility of such adaptation is due to the dependence of thermodynamic, chemical, and kinetic constants on temperature. This dependence, in general, determines the direction and speed of chemical reactions, conformational transitions of biological maodomolecules, phase transitions of lipids, changes in membrane permeability and other processes, the functioning of which ensures the vital activity of organisms at elevated temperatures.[ ...]

All this is only the first steps in the field of application of magnetic water in medicine. However, the already available information indicates the prospects for the use of magnetization of water systems in this area. A number of medical manifestations are possibly (hypothetically) related to the fact that the magnetization of water systems increases the permeability of membranes.[ ...]

It has been established that polymer films produced by the industry for ultrafiltration, ion exchange, as well as membranes made of collodion, gelatin, cellulose and other materials, have good selectivity, but low permeability (0.4 l/m h at a pressure of 40 am). Membranes prepared according to a special prescription from a mixture of cellulose acetate, acetone, water, magnesium perchlorate and hydrochloric acid (respectively 22.2; 66.7; 10.0; 1.1 and 0.1 weight percent) make it possible to desalinate water from 5, 25 to 0.05% NaCl and have a permeability of 8.5-18.7 l!m2 ■ h at an operating pressure of 100-140 am, their service life is at least 6 months. Electron microscopic studies of these membranes, since, according to preliminary calculations 1192], reverse osmosis can become competitive with other methods of water desalination with an increase in membrane permeability up to 5 m31 mg per day.[ ...]

The resting potential of the cell wall. The cell wall (shell) has a negative surface charge. The presence of this charge gives the cell wall distinct cation-exchange properties. The cell wall is characterized by predominant selectivity for Ca2+ ions, which plays an important role in the regulation of membrane permeability with respect to K and Na+ ions.[ ...]

Thus, the noted effects indicate that the culture fluid of the micromycete Fusarium oxysporum contains, in addition to fusaric acid, other components with high biological activity. The degree of pathogenicity of various isolates of phytopathogenic fungi can be assessed on the basis of determining changes in the permeability of plant cell membranes to ammonia.[ ...]

As a result, the formation of ATP is reduced or stopped, which leads to the suppression of processes that depend on the energy of respiration. The structure and selective permeability of membranes are also disturbed, which requires the expenditure of respiratory energy to maintain. These changes lead to a decrease in the ability of cells to absorb and retain water.[ ...]

On the other hand, the stabilization of the spatial structure of the protein and other biopolymers is carried out to a large extent due to the interaction: biopolymer - water. The water-protein-nucleic complex is considered the basis for the functioning of living systems, since only in the presence of these three components is the normal functioning of membranes possible. The selective permeability of membranes depends on the state of the water. Extrapolating the cluster model of water to biological systems, it can be shown that when the cluster is destroyed in certain areas of the membrane, a path for preferential transport opens. Structureless water, for example, prevents the behavior of protons near the membrane, while protons propagate rapidly along a structured framework.[ ...]

A scheme for continuous gas analysis using an ion-selective electrode is described, which can be used to determine the content of NH3, HCl, and HP in gases. In the review of the work of the NBS of the USA, among other methods of certification of reference gases (mixtures), the method of certification using ion-selective electrodes for gases of NSI and NR is also indicated. Of all the designs of ion-selective electrodes, the following is usually used: an ion-selective membrane separates two solutions - internal and external (tested). For electrical contact, an auxiliary electrode is placed in the internal solution, reversible to the ions of the internal solution, the activity of which is constant, as a result of which the potential is also constant. A potential difference arises on the inner and outer surfaces of the membrane, which depends on the difference in the activity of ions in the external and internal solutions. The theory of the appearance of the membrane potential is described in the work. Basically, the appearance of the potential is explained by the permeability of membranes either only for cations (cation-selective) or only for anions (anion-selective).

04/01/2012

Numerous articles about water mention the negative ORP values of internal body fluids and the energy of cell membranes (the life energy of the body).

Let's try to figure out what the speech is about and understand the meaning of these statements from a popular science point of view.

Many concepts and descriptions will be given in an abbreviated form, and more complete information can be obtained from Wikipedia or from the links indicated at the end of the article.

(Or cytolemma, or plasmalemma, or plasma membrane) separates the contents of any cell from the external environment, ensuring its integrity; regulate the exchange between the cell and the environment.

The cell membrane is so selective that without its permission, not a single substance from the external environment can even accidentally enter the cell. There is not a single useless, unnecessary molecule in the cell. The exits from the cell are also carefully controlled. The work of the cell membrane is essential and does not allow even the slightest error. The introduction of a harmful chemical into a cell, the supply or excretion of substances in excess, or the failure of waste excretion leads to cell death.

Free radicals attack

Barrier - provides a regulated, selective, passive and active metabolism with the environment. Selective permeability means that the permeability of a membrane to various atoms or molecules depends on their size, electrical charge, and chemical properties. Selective permeability ensures the separation of the cell and cellular compartments from the environment and supply them with the necessary substances.

The selective permeability of the membrane during passive transport is due to special channels - integral proteins. They penetrate the membrane through and through, forming a kind of passage.

For elements K, Na and Cl have their own channels. With respect to the concentration gradient, the molecules of these elements move in and out of the cell. When irritated, the sodium ion channels open, and there is a sharp influx of sodium ions into the cell. This results in an imbalance in the membrane potential. After that, the membrane potential is restored. Potassium channels are always open, through which potassium ions slowly enter the cell.

Transport - through the membrane, substances are transported into the cell and out of the cell. Transport through membranes provides: delivery of nutrients, removal of end products of metabolism, secretion of various substances, creation of ionic gradients, maintenance of optimal pH and the concentration of ions that are needed for the work of cellular enzymes.

There are four main mechanisms for the entry of substances into the cell or their removal from the cell to the outside: diffusion, osmosis, active transport and exo- or endocytosis. The first two processes are passive in nature, that is, they do not require energy; the last two are active processes associated with energy consumption.

In passive transport, substances cross the lipid bilayer without energy expenditure along the concentration gradient by diffusion.

Active transport requires energy, as it occurs against a concentration gradient. There are special pump proteins on the membrane, including the AT phase, which actively pumps potassium ions into the cell ( K+) and pump out sodium ions from it ( Na+).

Implementation of the generation and conduction of biopotentials. With the help of the membrane in the cell, a constant concentration of ions is maintained: the concentration of the ion K+ inside the cell is much higher than outside, and the concentration Na+ much lower, which is very important, since it maintains the potential difference across the membrane and generates a nerve impulse.

Cell labeling- there are antigens on the membrane that act as markers - "labels" that allow you to identify the cell. These are glycoproteins (that is, proteins with branched oligosaccharide side chains attached to them) that play the role of "antennas". Due to the myriad of side chain configurations, it is possible to make a specific marker for each cell type. With the help of markers, cells can recognize other cells and act in concert with them, for example, when forming organs and tissues. It also allows the immune system to recognize foreign antigens.

action potential

action potential- a wave of excitation moving along the membrane of a living cell in the process of transmitting a nerve signal.

In essence, it represents an electrical discharge - a quick short-term change in potential on a small section of the membrane of an excitable cell (neuron, muscle fiber or glandular cell), as a result of which the outer surface of this section becomes negatively charged with respect to neighboring sections of the membrane, while its inner surface becomes positively charged with respect to neighboring regions of the membrane.

action potential is the physical basis of a nerve or muscle impulse that plays a signal (regulatory) role.

Action potentials may differ in their parameters depending on the type of cell and even on different parts of the membrane of the same cell. The most characteristic example of differences is the action potential of the heart muscle and the action potential of most neurons.

However, at the heart of any action potential are the following phenomena:

The membrane of a living cell is polarized- its inner surface is negatively charged in relation to the outer one due to the fact that in the solution near its outer surface there are more positively charged particles (cations), and near the inner surface there are more negatively charged particles (anions).
The membrane has selective permeability- its permeability for various particles (atoms or molecules) depends on their size, electric charge and chemical properties.
The membrane of an excitable cell is able to quickly change its permeability for a certain type of cations, causing the transition of a positive charge from the outside to the inside.

The polarization of the membrane of a living cell is due to the difference in the ionic composition of its inner and outer sides.

When the cell is in a calm (unexcited) state, ions on opposite sides of the membrane create a relatively stable potential difference, called the resting potential. If you introduce an electrode inside a living cell and measure the resting membrane potential, it will have a negative value (of the order of -70..-90 mV). This is explained by the fact that the total charge on the inner side of the membrane is significantly less than on the outer one, although both sides contain both cations and anions.

Outside - an order of magnitude more sodium, calcium and chlorine ions, inside - potassium ions and negatively charged protein molecules, amino acids, organic acids, phosphates, sulfates.

It must be understood that we are talking about the charge of the membrane surface - in general, the environment both inside and outside the cell is neutrally charged.

The active properties of the membrane, which ensure the occurrence of an action potential, are based mainly on the behavior of voltage-dependent sodium ( Na+) and potassium ( K+) channels. The initial phase of AP is formed by the incoming sodium current, later potassium channels open and the outgoing K+- the current returns the membrane potential to the initial level. The initial concentration of ions is then restored by the sodium-potassium pump.

In the course of PD, the channels pass from state to state: Na+ there are three channels of the main states - closed, open and inactivated (in reality, the matter is more complicated, but these three are enough to describe), K+ two channels - closed and open.

conclusions

1. ORP of the intracellular fluid really has a negative charge

2. The energy of cell membranes is related to the speed of transmission of the nerve signal, and the opinion about the "recharging" of the intracellular fluid with water with an even more negative ORP seems doubtful to me. However, if we assume that on the way to the cell, the water will significantly lose its ORP potential, then this statement has a completely practical meaning.

3. Violation of the membrane due to an unfavorable environment leads to cell death

PERMEABILITY- the ability of cells and tissues to absorb, release and transport chemicals, passing them through cell membranes, vascular walls and epithelial cells. Living cells and tissues are in a state of continuous chemical exchange. substances with the environment. The main barrier (see Barrier functions) to the movement of substances is the cell membrane. Therefore, historically, P.'s mechanisms were studied in parallel with the study of the structure and function of biological membranes (see Biological membranes).

There are passive P., active transport of substances and special cases of P. associated with phagocytosis (see) and pinocytosis (see).

In accordance with the membrane theory of P., passive P. is based on various types of diffusion of a substance through cell membranes (see Diffusion

where dm is the amount of substance diffusing during the time dt through the area S; dc/dx - substance concentration gradient; D is the diffusion coefficient.

Rice. Fig. 1. Molecular organization of an ionophore antibiotic (valinomycin): a - structural formula of a valinomycin molecule containing six dextrorotatory (D) and six levorotatory (L) amino acids, all side groups [-CH 3 -CH (CH 3) 2] are hydrophobic; b - schematic representation of the spatial configuration of the complex of valinomycin with a potassium ion (in the center). Some of the carbonyl groups of the complex form hydrogen bonds with nitrogen atoms, while others form coordination bonds with the cation (potassium ion). Hydrophobic groups form the outer hydrophobic sphere of the complex and ensure its solubility in the hydrocarbon phase of the membrane; 1 - carbon atoms, 2 - oxygen atoms, 3 - cation (potassium ion), 4 - nitrogen atoms, 5 - hydrogen bonds, 6 - coordination bonds. The potassium ion "captured" by the valinomycin molecule is carried by this molecule through the cell membrane and released. In this way, the selective permeability of the cell membrane for potassium ions is ensured.

In the study of P., cells for a solute instead of a concentration gradient use the concept of the difference in concentrations of a diffusing substance on both sides of the membrane, and instead of the diffusion coefficient, the permeability coefficient (P), which also depends on the thickness of the membrane. One of the possible ways of penetration of substances into the cell is their dissolution in the lipids of cell membranes, which is confirmed by the existence of a direct proportional relationship between the permeability coefficient of a large class of chemical. compounds and the distribution coefficient of the substance in the oil-water system. At the same time, water does not obey this dependence, its penetration rate is much higher and is not proportional to the distribution coefficient in the oil-water system. For water and low molecular weight substances dissolved in it, the most probable way of P. is the passage through membrane pores. Thus, the diffusion of substances across the membrane can occur by dissolving these substances in the lipids of the membrane; by passing molecules through polar pores formed by polar, charged groups of lipids and proteins, as well as by passing through uncharged pores. Special types are facilitated and exchange diffusion provided by proteins and fat-soluble carrier substances that are able to bind the transported substance on one side of the membrane, diffuse with it through the membrane and release it on the other side of the membrane. The rate of transfer of a substance through the membrane in the case of facilitated diffusion is much higher than in simple diffusion. The role of specific ion carriers can be performed by some antibiotics (valinomycin, nigericin, monensin, and a number of others), which are called ionophores (see Ionophores). The molecular organization of complexes of ionophore antibiotics with cations has been deciphered. In the case of valinomycin (Fig. 1), it was shown that after binding to the potassium cation, the peptide molecule changes its conformation, acquiring the form of a bracelet with an inner diameter of approx. 0.8 nm, in Krom the potassium ion is retained as a result of ion-dipole interactions.

A common type of passive P. of cell membranes for polar substances is P. through the pores. Although direct observation of pores in the lipid layer of the membrane is a difficult task, experimental data indicate their real existence. Data on the osmotic properties of cells also testify in favor of the real existence of pores. The value of osmotic pressure in solutions surrounding the cell can be calculated by the formula:

π=σCRT,

where π - osmotic pressure; C is the concentration of the solute; R is the gas constant; T is the absolute temperature; σ is the reflection coefficient. If the rate of passage of a solute molecule through the membrane is commensurate with the rate of passage of water molecules, then the magnitude of the forces will be close to zero (there is no osmotic change in the volume of the cell); if the cell membrane is impermeable to a given substance, then the value of σ tends to 1 (the osmotic change in the volume of the cell is maximum). The rate of penetration of molecules through the cell membrane depends on the size of the molecule, and thus, by selecting molecules of a certain size and observing the change in cell volume in a solution of a given substance, one can determine the size of cell pores. For example, the squid axon membrane is slightly permeable to glycerol molecules, which have a radius of approx. 0.3 nm, but permeable to substances with smaller molecular sizes (table). Similar experiments with other cells showed that the pore sizes in cell membranes, in particular, in the membranes of erythrocytes, Escherichia coli, intestinal epithelial cells, etc., fit quite accurately within 0.6-0.8 nm.

Living cells and tissues are characterized by another way of penetration of substances into the cell and out of it - the active transport of substances. Active transport is the transfer of a substance through a cell (or intracellular) membrane (transmembrane active transport) or through a layer of cells (transcellular active transport) flowing against an electrochemical gradient (see Gradient). i.e., with the expenditure of free energy of the body (see Metabolism and Energy). The molecular systems responsible for the active transport of substances are located in the cell (or intracellular) membrane. In the cytoplasmic membranes of cells involved in active ion transport - muscle cells, neurons, erythrocytes, kidney cells - there is a significant amount of the enzyme Na +, Independent ATPase, which is actively involved in the mechanisms of ion transport (see Ion Transport). The mechanism of functioning of this enzyme is best studied on erythrocytes and axons, which have a pronounced ability to accumulate potassium ions and remove (pump out) sodium ions. It is assumed that erythrocytes contain a molecular device - a potassium-sodium pump (potassium-sodium pump), which provides selective absorption of potassium ions and selective removal of sodium ions from the cell, and the main element of this pump is Na +, K + -ATPase. The study of the properties of the enzyme showed that the enzyme is active only in the presence of potassium and sodium ions, with sodium ions activating the enzyme from the side of the cytoplasm, and potassium ions from the side of the surrounding solution. A specific inhibitor of the enzyme is the cardiac glycoside ouabain. Other transport ATPases have also been found, in particular, transporting Ca +2 ions.

In mitochondrial membranes, a molecular system is known that ensures the pumping out of hydrogen ions, the enzyme H + -ATP-ase, and in the membranes of the sarcoplasmic reticulum, the enzyme Ca ++ -ATP-ase. Mitchell (P. Mitchell) - the author of the chemiosmotic theory of oxidative phosphorylation in mitochondria (see Phosphorylation) - introduced the concept of "secondary transport of substances", which is carried out due to the energy of the membrane potential and (or) the pH gradient. If for ionic ATPases, the antigradient movement of ions and ATP utilization are provided by the same enzyme system, then in the case of secondary active transport, these two events are provided by different systems and can be separated in time and space.

Penetration into cells of large protein macromolecules, nucleic to-t. cellular enzymes and whole cells is carried out according to the mechanism of phagocytosis (capture and absorption of large solid particles by the cell) and pinocytosis (capture and absorption by part of the cell surface of the surrounding fluid with substances dissolved in it).

P. cell membranes is more important for the functioning of cells and tissues.

Active transport of ions and the accompanying absorption of water in the cells of the renal epithelium occurs in the proximal tubules of the kidney (see Kidneys). Up to 1800 liters of blood passes through the kidneys of an adult every day. At the same time, proteins are filtered out and remain in the blood, 80% of salts and water, as well as all glucose, are returned to the bloodstream. It is believed that the primary cause of this process is the transcellular active transport of sodium ions, provided by Na+ K+-dependent ATP-ase, localized in the cell membranes of the basal epithelium. If in the channel of the renal proximal tubule the concentration of sodium ions is approx. 100 mmol / l, then inside the cell it does not exceed 37 mmol / l; as a result, the passive flow of sodium ions is directed into the cell. Passive penetration of cations into the cytoplasm is also facilitated by the presence of a membrane potential (the inner surface of the membrane is negatively charged). That. sodium ions penetrate into the cell passively in accordance with the concentration and electrical gradients (see Gradient). The release of ions from the cell into the blood plasma is carried out against the concentration and electrical gradients. It has been established that it is in the basement membrane that the sodium-potassium pump is localized, which ensures the removal of sodium ions. It is assumed that chloride anions move after sodium ions through the intercellular space. As a result, the osmotic pressure of the blood plasma increases, and water from the channel of the tubule begins to flow into the blood plasma, providing the reabsorption of salt and water in the renal tubules.

Various methods are used to study passive and active P.. The method of labeled atoms has become widely used (see Isotopes, Radioactive drugs, Radioisotope research). The isotopes 42 K, 22 Na and 24 Na, 45 Ca, 86 Rb, 137 Cs, 32 P, and others are used to study the ionic P. of cells; to study the P. of water - deuterium or tritium water, as well as water labeled with oxygen (18O); for the study of P. sugars and amino acids - compounds labeled with carbon 14 C or sulfur 35 S; for the study of P. proteins - iodinated preparations labeled with 1 31 I.

Vital dyes are widely applied at P.'s research. The essence of the method is to observe under a microscope the rate of penetration of dye molecules into the cell. For most vital dyes (neutral red, methylene blue, rhodamine, etc.), observations are made in the visible part of the spectrum. Fluorescent compounds are also used, among them sodium fluorescein, chlortetracycline, murexide, and others. In the study of muscles, it was shown that the pigmentation of dye molecules depends not only on the properties of the cell membrane, but also on the sorption capacity of intracellular structures, most often proteins and nucleic acids. -t, with which dyes bind.

The osmotic method is used to study the P. of water and substances dissolved in it. At the same time, using a microscope or measuring the light scattering of a suspension of particles, a change in the volume of cells is observed depending on the tonicity of the surrounding solution. If the cell is in a hypertonic solution, then water from it goes into solution and the cell shrinks. The opposite effect is observed in the hypotonic solution.

Increasingly, potentiometric methods are used to study P. of cell membranes (see Microelectrode research method, Electrical conductivity of biological systems); A wide range of ion-specific electrodes makes it possible to study the transport kinetics of many inorganic ions (potassium, sodium, calcium, hydrogen, etc.), as well as some organic ions (acetates, salicylates, etc.). All types of P. cellular membranes are to some extent characteristic of multicellular tissue membrane systems - the walls of blood vessels, the epithelium of the kidneys, the mucous membrane of the intestines and stomach. At the same time, P. of the vessels is characterized by some features that are manifested in the violation of vascular P. (see below).

Pathological physiology of vascular permeability

The term "vascular permeability" was used to designate histohematic and transcapillary metabolism, the distribution of substances between the blood and tissues, tissue P., hemolymphatic transition of substances, and other processes. Some researchers use this term to refer to the trophic function of capillary-connective tissue structures. The ambiguity of the use of the term was one of the reasons for the inconsistency of views on a number of issues, especially those related to the regulation of vascular P. In the 70s. 20th century the term "vascular permeability" began to use Ch. arr. to indicate the selective permeability, or barrier-transport function, of the walls of blood microvessels. There is a tendency to attribute to vascular P. also P. the walls of not only microvessels (blood and lymph), but also large vessels (up to the aorta).

Changes in vascular P. are observed hl. arr. in the form of an increase in selective P. for macromolecules and blood cells. A typical example of this is exudation (see). Vascular P.'s decrease is connected generally with proteinaceous impregnation and the subsequent inspissation of vascular walls that is observed, for example, at an idiopathic hypertensia (see).

There is an opinion about the possibility of P.'s disturbance of the vascular wall mainly in the direction of the interstitium or from the interstitium into the blood. However, the predominant movement of substances in one direction or another relative to the vascular wall does not yet prove its connection with the state of the barrier-transport function of the vascular wall.

Principles for studying vascular permeability disorders

An assessment of the state of vascular P. must be carried out taking into account the fact that the vascular wall provides a distinction and functional connection between two adjacent media (blood and interstitial environment), which are the main components of the internal environment of the body (see). The exchange between these adjacent environments as a whole is carried out due to microcirculation (see Microcirculation), and the vascular wall with its barrier-transport function acts only as the basis of organ specialization of histohematological metabolism. Therefore, the method of studying the state of vascular P. can be considered adequate only when it allows assessing the qualitative parameters of histohematic metabolism, taking into account their organ specificity and regardless of the state of organ microcirculation and the nature of metabolic processes that form outside the vascular wall. From this point of view, the most adequate of the existing methods is the electron microscopic method for studying vascular P., which makes it possible to directly observe the ways and mechanisms of the penetration of substances through the vascular wall. Particularly fruitful was the combination of electron microscopy with the so-called. tracing indicators, or tracers, marking the paths of their movement through the vascular wall. As such indicators, any non-toxic substances detected using electron microscopy or special techniques (histochemical, radioautographic, immunocytochemical, etc.) can be used. For this purpose, the iron-containing protein ferritin, various enzymes with peroxidase activity, colloidal charcoal (purified black ink), etc. are used.

Of the indirect methods for studying the state of the barrier-transport function of the walls of blood vessels, the most widely used is the registration of penetration through the vascular wall of natural or artificial indicators that weakly or do not penetrate the wall at all under normal conditions. In violation of microcirculation, which is often observed in violation of vascular P., these methods may be uninformative, and then they should be combined with methods for monitoring the state of microcirculation, for example. using biomicroscopy or easily diffusing indicators, the histohematic exchange of which does not depend on the state of vascular P. and tissue metabolism. The disadvantage of all indirect methods based on recording the accumulation of indicator substances outside the vascular bed is the need to take into account the mass of factors that can significantly affect the level of the indicator in the area under study. In addition, these methods are quite inertial and do not allow studying short-term and reversible changes in vascular P., especially in combination with a change in microcirculation. These difficulties can be partially overcome by using the method of labeled vessels, which is based on determining the penetration into the vascular wall of a weakly diffusible indicator that accumulates in the wall and stains it. The painted (labeled) sites come to light by means of a light microscope and are the proof of violation of P. of an endothelium. As an indicator, colloidal charcoal can be used, which forms easily detectable dark accumulations in places of gross violation of the endothelial barrier. Changes in the activity of microvesicular transport are not recorded by this method, and it is necessary to use other indicators carried through the endothelium by microvesicles.

The possibilities of studying disorders of vascular P. in a clinical setting are more limited, since most methods based on the use of micromolecular easily diffusing indicators (including radioisotopes) do not allow one to unambiguously judge the state of the barrier-transport function of the walls of blood vessels.

A method based on the determination of quantitative differences in the protein content in arterial and venous blood samples taken simultaneously is relatively widely used (see Landis test). When calculating the percentage of protein loss in the blood during its transition from the arterial to the venous bed, it is necessary to know the percentage of water loss, which is determined by the difference in the hematocrit of the arterial and venous blood. In their studies on healthy people, V. P. Kaznacheev and A. A. Dzizinsky (1975) derived the following values as indicators of normal P. of the vessels of the upper limb: for water, an average of 2.4–2.6%, for protein, 4– 4.5%, i.e. when passing through the vascular bed 100 ml of blood in the lymph. the riverbed enters approx. 2.5 ml of water and 0.15-0.16 g of protein. Consequently, at least 200 liters of lymph should be formed in the human body per day, which is ten times higher than the actual value of daily lymph production in the body of an adult. It is obvious that the disadvantage of the method is the assumption that, according to Krom, the differences in the hematocrit of arterial and venous blood are explained only by a change in the content of water in the blood due to its exit from the vascular bed.

In a wedge practice, the state of regional vascular P. is often judged by the presence of interstitial or cavitary accumulations of free fluid rich in protein. However, when assessing the state of vascular P., for example. in the abdominal cavity, an erroneous conclusion can be made, since the metabolic microvessels of these organs and tissues are normally characterized by high P. for macromolecules due to the discontinuity or porosity of their endothelium. An increase in filtration pressure in such cases leads to the formation of a protein-rich effusion. The venous sinuses and sinusoids are especially permeable to protein molecules.

It should be noted that the increased output of plasma proteins into the tissue and the development of tissue edema (see) do not always accompany an increase in vascular P. Microvessels (capillaries and venules), the endothelium of which is normally poorly permeable to macromolecules, acquire endothelial defects; through these defects easily enter the subendothelial space introduced into the bloodstream indicators - macromolecules and microparticles. However, there are no signs of tissue edema - the so-called. edematous form of impaired vascular permeability. A similar phenomenon is observed, for example, in the muscles of animals during the development of a neurodystrophic process in them associated with transection of the motor nerve. Similar changes in human tissues are described, for example, during aging and diabetes mellitus, when the so-called. acellular capillaries, i.e., metabolic microvessels with partially or completely desquamated endothelial cells (there are also no signs of tissue edema). All these facts indicate, on the one hand, the relativity of the relationship between tissue edema and an increase in vascular P., and, on the other hand, the existence of extravascular mechanisms responsible for the distribution of water and substances between the blood and tissues.

Factors of impaired vascular permeability

Factors of violation of vascular permeability are conventionally divided into two groups: exogenous and endogenous. Exogenous factors of violation of vascular P. of various nature (physical, chemical, etc.) are in turn divided into factors that directly affect the vascular wall and its barrier-transport function, for example, histamine introduced into the vascular bed, various toxins, etc. .), and factors of violation P. of indirect action, the effect of which is mediated through endogenous factors.

Already known endogenous factors of vascular P.'s disturbance (histamine, serotonin, kinins) began to include a large number of others, in particular prostaglandins (see), and the latter not only increase vascular P., but also enhance the effect of other factors; many of the endogenous factors are produced by various enzymatic systems of the blood (the Hageman factor system, the complement system, etc.).

Increase vascular P. and immune complexes. From the factor responsible for the "delayed" increase in vascular P. during the development of the Arthus phenomenon, Yosinaga (1966) singled out pseudoglobulin; Kuroyanagi (1974) discovered a new P. factor, designated by him as Ig-PF. In its properties, it differs significantly from histamine, kinins, anaphylatoxin and kallikrein, acts longer than histamine and bradykinin, and is inhibited by vitamins K1 and K2.

Many factors of disturbance of vascular P. are produced by leukocytes. Thus, a protease is associated with the surface of neutrophils, which forms a neutral peptide mediator from plasma proteins that increases vascular P. The protein substrate of the protease has a mol. weight (mass) 90,000 and different from kininogen.

Lysosomes and specific granules of blood cells contain cationic proteins that can disrupt vascular P. Their action is mediated by mast cell histamine.

Various endogenous factors of disturbance of vascular P. act in fabrics simultaneously or sequentially, causing in. vascular P. phase shifts. In this regard, early, delayed and late changes in vascular P. are distinguished. The early phase is the phase of the action of histamine (see) and serotonin (see). The second phase develops after a period of imaginary well-being, 1-3 hours after the primary injury - a delayed, or delayed phase; its development is caused by action of kinins (see) or prostaglandins. The development of these two phases depends on the level of complement and is inhibited by anticomplementary immune serum. A day after the damage, the third phase develops, associated with the action of cyto- and proteolytic enzymes released from the lysosomes of leukocytes and lymphocytes. Depending on the nature of the primary damaging agent, the number of phases can be different. In an early phase vascular P. is broken by hl. arr. at the level of venules, in subsequent phases the process extends to the capillary bed and arterioles.

Reception of permeability factors by the vascular wall. Endogenous factors of P.'s disturbance represent the most important group of causes of vascular P.'s disturbance. Some of them are in ready-made form in the tissues (histamine, serotonin) and, under the influence of various pathogenic influences, are released from the depot, which are mast cells and blood cells (basophils, platelets). Other factors are the product of different biochem. systems both at the site of primary damage and at a distance from it.

The questions of the origin of P.'s factors are in themselves important for solving practical problems of the prevention and treatment of disorders of vascular P. However, the appearance of P.'s factor is not yet sufficient for vascular P.'s disturbance. “Seen”, i.e., prescribed, by the vascular wall (unless it has a destructuring ability like cytolytic agents). It is known, for example, that histamine, introduced into the general circulation, disrupts vascular P. only in certain organs and tissues, while in other tissues (brain, lung tissue, endoneurium, etc.) it is not effective. In frogs, the introduction of serotonin and bradykinin into the vascular bed does not cause disturbance of vascular P at all. However, the reasons for the inefficiency of histamine in both cases are different.

According to modern data, the endothelium of the metabolic microvessels of warm-blooded animals and humans is sensitive to a large number of various agents, i.e., it is characterized by a high receptor capacity. As for histamine, one of the main factors of P., which causes an acute and significant (albeit short-term) disturbance of vascular P., experimental data indicate the presence in the endothelium of two types of histamine receptors H1 and H2, which play different roles in the mechanism of action of histamine. It is the stimulation of H1 receptors that leads to the disruption of vascular P., which is characteristic of the action of histamine.

Under the action of some endogenous factors P., in particular histamine, tachyphylaxis is observed (see) and repeated use (after 30 minutes) of the agent does not violate vascular P. in some cases this may be the case. In the case of histamine, the mechanism of tachyphylaxis, according to some reports, has an extra-receptor localization. This is proved, in particular, by the fact of the development of cross-tachyphylaxis, when the use of histamine leads to the development of endothelial resistance not only to histamine itself, but also to lanthanum salts that bypass receptors. The occurrence of cross tachyphylaxis may be one of the reasons for the inefficiency of individual P. factors acting simultaneously or sequentially.

Ultrastructural bases and effector mechanisms of vascular permeability disorders

Rice. Fig. 2. Ways and mechanisms of transcapillary metabolism under normal conditions (a) and pathology (b): 1 - transcellular diffusion; 2 - diffusion and ultrafiltration in the area of dense intercellular junctions; 3 - diffusion and ultrafiltration in the area of simple intercellular connections; 4 - microvesicular transport bypassing tight intercellular junctions; 3a and 4a - pathological intercellular channels of the "histamine gaps" type; 5 - microvesicular transport; 6 - formation of a transcellular channel by fusion of microvesicles; 7 - phagocytic vacuoles in pericytes; 8 - microparticles of the indicator of vascular permeability (BM - basement membrane, EN1, EN2, EN3 - endotheliocytes, PC - pericytes).

Electron microscopic studies revealed that morfol. the basis of vascular P.'s increase is the formation of wide channels in the area of intercellular connections in the endothelium (Fig. 2). Such channels, or "leaks", are often called histamine clefts, since their formation is typical of the action on the vascular wall of histamine and was first studied in detail precisely during its action. Histamine cracks are formed by hl. arr. in the walls of the venules of those organs and tissues where there are no low-permeable histohematic barriers such as the blood-brain barrier, etc. Local discrepancies in intercellular contacts were found in neuroregulatory disorders, mechanical, thermal, chemical and other types of tissue damage, under the action of various bioregulators (serotonin, bradykinin, prostaglandins E1 and E2, etc.). Violation of intercellular contacts occurs, albeit with great difficulty, in capillaries and arterioles, and even in larger vessels. The ease of formation of histamine gaps is directly proportional to the initial structural weakness of intercellular connections, the edge increases during the transition from arterioles to capillaries and from capillaries to venules, reaching a maximum at the level of postcapillary (pericytic) venules.

The inefficiency of histamine in disturbing the vascular P. of some organs is well explained precisely from the point of view of the development of tight junctions in the endothelium of the microvessels of these organs, for example. brain.

In theoretical and practical terms, the question of the effector mechanisms underlying the formation of structural defects such as histamine gaps is important. These ultrastructural shifts are typical for the initial phase of acute inflammation (see), when, according to I. I. Mechnikov (1891), an increase in vascular P. is biologically expedient, since this ensures an increased exit of phagocytes to the site of damage. It can be added that an increased plasma output in such cases is also advisable, since in this case antibodies and non-specific protection agents are delivered to the focus. Thus, an increase in vascular P. in the focus of inflammation can be considered as a specific state of the barrier-transport function of the walls of micro-vessels, adequate to the new conditions for the existence of tissue, and a change in vascular P. during inflammation and similar situations is not a violation, but a new one. a functional state that contributes to the restoration of disturbed tissue homeostasis. It should be borne in mind that in some organs (liver, spleen, bone marrow), where, in accordance with the characteristics of organ functions, there is a continuous metabolic flow of cells and macromolecules, intercellular "leaks" are normal and permanent formations, which are exaggerated histamine gaps, but unlike from true histamine gaps are capable of long-term existence. True histamine gaps are formed in the very first seconds after exposure to the mediators of acute inflammation on the endothelium and, for the most part, after 10-15 minutes. are closed. The mechanism of formation of histamine gaps has a protective, phylogenetically determined nature and is associated with a stereotyped reaction at the cellular level, triggered by stimulation of different types of receptors.

The nature of this stereotyped reaction remained unexplored for a long time. I. I. Mechnikov believed that an increase in vascular P. during inflammation is associated with a reduction in endothelial cells. However, later it was found that endotheliocytes in the vessels of warm-blooded animals do not belong to the category of cells that actively change their shape like muscle cells. Rowley (D. A. Rowley, 1964) suggested that the divergence of endotheliocytes is a consequence of an increase in intravascular pressure and the associated overstretching of the endothelium. Direct measurements have proved the unacceptability of this hypothesis in relation to venules and capillaries, however, for arterial vessels it has a certain value, because if the tonic activity of the muscular membrane is disturbed, high intravascular pressure can really cause overstretching of the endothelium and damage to intercellular contacts. But in this case, the appearance of histamine gaps in the intima is not always associated with the action of transmural pressure. Robertson and Kairallah (A. L. Robertson, P. A. Khairallah, 1972) in experiments on an isolated segment of the abdominal aorta of a rabbit showed that wide gaps in the endothelium are formed under the influence of angiotensin II in places of rounding and shortening of endotheliocytes. Similar morfol. shifts were also found in the endothelium of metabolic microvessels of the skin with topical application of angiotensin II, prostaglandin E1 and serum triglycerides.

O. V. Alekseev and A. M. Chernukh (1977) found in endotheliocytes of metabolic microvessels the ability to rapidly increase the content in the cytoplasm of microfibrillar structures similar in their morphol. features with actin microfilaments. This reversible phenomenon (the so-called phenomenon of operational structuralization of the microfibrillar apparatus) develops under the influence of factors that cause the formation of wide intercellular gaps. The reversibility of the phenomenon in the case of the use of histamine makes it difficult to detect and well explains the short duration and reversibility of the existence of histamine gaps. With the help of cytochalasin-B, which blocks the formation of actin microfibrils, the pathogenetic significance of this phenomenon in the mechanism of formation of intercellular histamine gaps is revealed. These facts indicate that endotheliocytes have a latent ability to contract, which is realized in conditions when the previous level of vascular P. is inadequate and a relatively rapid and reversible change is required. Vascular P.'s change acts, thus, as a special act of biol. regulation, which ensures the adaptation of the barrier-transport function of the vascular endothelium in accordance with new local needs that have arisen sharply in connection with changes in the conditions of tissue vital activity.

The presence in the tissues of the mechanism of change in vascular P. can be attributed to the so-called. risk factors, since the operation of this mechanism in inadequate conditions can cause a violation of tissue homeostasis and organ function, and not a manifestation of the action of adaptive-protective mechanisms. The main ways of disturbance of vascular P. are presented on the scheme. Changes in vascular P. are based on mechanisms that not only lead to the formation of intercellular channels (histamine gaps), but also affect the activity of the cell surface (i.e., microvesiculation and microvesicular transport, vacuolization and microbubble formation). The result may be perforation of endotheliocytes with the formation of more or less extensive and long-term transcellular channels.

Great importance in the mechanisms of disturbance of vascular P. is attached to local changes in the surface electric charge, especially on membranes that close pores in fenestrated capillaries (eg, renal glomeruli). According to some data, the change in charge alone can be the basis for increasing the yield of proteins from the glomerular capillaries. That. the limitedness of the theory of pores is proved; Under conditions of pathology, the effect of increasing the porosity of the endothelium can be achieved in different ways: by the formation of intercellular channels such as histamine gaps; increased microvesicular and intravacuolar transport; perforation of endothelial cells based on increased microvesiculation, vacuolization or microbubble formation in the endothelium; microfocal destruction of endotheliocytes; desquamation of endotheliocytes; change fiz.-chem. properties of the surface of endotheliocytes, etc. (see Microcirculation ]]). The same effect can also be achieved due to extra-wall mechanisms, in particular, due to a change in the binding ability of blood macromolecules, with which almost all known indicators used to assess the state of vascular P. interact. the listed mechanisms. So, for example, histamine increases the porosity of the vascular wall due to the formation of histamine gaps in the endothelium of venules, as well as by influencing the surface of endotheliocytes and the transport processes associated with its activity and ultrastructural transformations (the formation of transcellular pores, fenestrations, microtubules, etc.). It should be taken into account that this often changes the thickness of endotheliocytes and the depth of intercellular gaps, which can significantly affect the permeability of the vascular wall as a diffusion barrier. The question of behavior in conditions of biochemical pathology has not been studied at all. mechanisms that prevent or, conversely, promote the penetration of substances through the vascular wall, especially biologically active ones. It is known, for example, that the endotheliocytes of the brain capillaries normally have an enzymatic activity that destroys serotonin and thereby prevents its penetration both from the blood into the brain and in the opposite direction. The endothelium of the pulmonary capillaries contains kininase II, which is localized in micropinocytic vesicles and ensures the destruction of bradykinin and, at the same time, the conversion of angiotensin I to angiotensin II (hypertension). Thus, the endothelium exercises a kind of control over the balance of humoral bioregulators and actively influences the histohematic metabolism of these agents.

Targeted intervention is carried out at three levels (see diagram). The first level - the impact on the process of formation of causal (receptible) factors - is practically not used, although there are separate medications that can act at this level. For example, reserpine affects the deposition of P.'s disturbance factors in mast cells, which are the main source of mediators of acute inflammation (histamine and serotonin); antiprostaglandin agents inhibit the synthesis of prostaglandins - acetylsalicylic acid, etc.

The second level is the main one in the practice of developing means for the prevention and treatment of disorders of vascular P. It corresponds to the process of reception of the causative factor. A significant number of antihistamine, antiserotonin, and antibradykinin drugs are used to prevent vascular P.'s disorders caused by the corresponding mediators. The advantage and at the same time the disadvantage of these drugs, acting by blockade of specific receptors, is their high specificity. Such specificity does them inefficient in the conditions of multiplicity etiol. factors acting simultaneously or sequentially, which is usually observed in a wedge. practice. It is also important that the exclusion of the action of one or several factors that determine the development of one phase of vascular P.'s disturbance does not exclude the development of subsequent phases. These shortcomings can be overcome through intervention at the third level.

The third level is the effect on intracellular (subcellular) effector mechanisms through which the action of P.'s factors is directly realized, and they are the same for the action of various pathogenic agents. The reality and effectiveness of this approach can be demonstrated experimentally by using a substance (cytochalasin-B) that inhibits the phenomenon of operational structuralization of the microfibrillar apparatus in endotheliocytes (formation of actin gel and actin microfibrils).

In a wedge In practice, in order to normalize increased vascular P., vitamin P is used (see Bioflavonoids) and calcium salts. However, these drugs cannot be considered as specific to lay down. agents in violation of vascular P., although they have a general strengthening effect on histohematic barriers, membranes and the wall of blood vessels in particular.

Various endogenous P. factors can be used to increase vascular P., for example. histamine, or substances that release them from tissue depots.

Bibliography: Alekseev O. V. Microcirculatory homeostasis, in the book: Homeostasis, ed. P. D. Horizontova, p. 278, M., 1976; Antonov VF Lipids and ion permeability of membranes, M., 1982; Biological membranes, ed. D. S. Parsons, trans. from English, M., 1978; D e Robert tis E., Novinsky V. and S and e with F. Biology of the cell, trans. from English, M., 1967; Living cell, trans. from English, ed. G. M. Frank, p. 130, Moscow, 1962; K a z-nacheevV.P. and D z and z and N with to and y A. A. Clinical pathology of transcapillary exchange, M., 1975; Light foot E. Transfer phenomena in living systems, trans. from English, M., 1977; Lakshminaraya nay and x N. Membrane electrodes, trans. from English, L., 1979; Lev A. A. Modeling of ionic selectivity of cellular membranes, L., 1976; Ovchinnikov Yu. A., Ivanov V. T. and III to r about b A. M. Membrane-active complexones, M., 1974; Structure and function of the cell, trans. from English, ed. G. M. Frank, p. 173, M., 1964; Troshin A. S. The problem of cell permeability, M. - L., 1956; Chernukh A. M., Alexandrov P. N. and Alekseev O. V. Microcirculation, M., 1975; Di Rosa M., Giroud J. R. a. W 1 1-loughby D. A. Studies of the media-tors of the acute inflammatory response induced ln rats in different sites by carra-geenan and turpentine, J. Path., v. 104, p. 15, 1971; M a j n o G. a. P a 1 a-de G. E. Studies on inflammation, I. The effect of histamine and serotonin on vascu-lar permeability, an electron microscopic study, J. biophys. biochem. Cytol., v. 11, p. 571, 1961; M a j n o G., S h e a S. M. a. Leventhal M. Endothelial cont-raction induced by histamine-type medi-ators, J. Cell Biol., v. 42, p. 647, 1969: Shimamoto T. Contraction of endothelial cells as a key mechanism in atherogenesis and treatment of atherosclerosis with endothelial cell relaxants, in: Atherosclerosis III, ed. by G. Schettler a. A. Weizel, p. 64, V.-N. Y., 1974.

B. F. Antonov; O. V. Alekseev (path. Phys.).

Membrane transport

The transport of substances into and out of the cell, as well as between the cytoplasm and various subcellular organelles (mitochondria, nucleus, etc.) is provided by membranes. If the membranes were a blind barrier, then the intracellular space would be inaccessible to nutrients, and waste products could not be removed from the cell. At the same time, with complete permeability, the accumulation of certain substances in the cell would be impossible. The transport properties of the membrane are characterized by semipermeability: some compounds can penetrate through it, while others cannot:

Membrane permeability for various substances

One of the main functions of membranes is the regulation of the transfer of substances. There are two ways of transporting substances across the membrane: passive and active transport:

Passive transport. If a substance moves through the membrane from a region of high concentration to a low concentration (i.e., along the concentration gradient of this substance) without consuming energy by the cell, then such transport is called passive, or diffusion. There are two types of diffusion: simple and facilitated.

Simple diffusion is characteristic of small neutral molecules (H2O, CO2, O2), as well as hydrophobic low molecular weight organic substances. These molecules can pass without any interaction with membrane proteins through the pores or channels of the membrane as long as the concentration gradient is maintained.

Facilitated diffusion. It is characteristic of hydrophilic molecules that are also transported through the membrane along a concentration gradient, but with the help of special membrane proteins - carriers. Facilitated diffusion, in contrast to simple diffusion, is characterized by high selectivity, since the carrier protein has a binding center complementary to the transported substance, and the transfer is accompanied by conformational changes in the protein. One of the possible mechanisms of facilitated diffusion can be as follows: a transport protein (translocase) binds a substance, then approaches the opposite side of the membrane, releases this substance, assumes its original conformation, and is again ready to perform the transport function. Little is known about how the movement of the protein itself is carried out. Another possible mechanism of transfer involves the participation of several carrier proteins. In this case, the initially bound compound itself passes from one protein to another, sequentially binding to one or another protein until it is on the opposite side of the membrane.

Cell membranes. Membrane permeability