Creation

Concentration gradient transport. Concentration gradient of sodium (Na) as a driving force of membrane transport. Dx - concentration gradient

Equilibrium potential- such a value of the transmembrane difference in electric charges, at which the current of ions into and out of the cell becomes the same, i.e. in fact, the ions do not move.

The concentration of potassium ions inside the cell is much higher than in the extracellular fluid, while the concentration of sodium and chlorine ions, on the contrary, is much higher in the extracellular fluid. Organic anions are large molecules that do not pass through cell membrane.

This concentration difference or concentration gradient is an driving force for the diffusion of dissolved ions to a region of lower concentration or, in accordance with the second law of thermodynamics, to a lower energy level. Thus, sodium cations should diffuse into the cell, and potassium cations - from it.

It is necessary to take into account the permeability of the cell membrane for various ions, and it changes depending on the state of cell activity. At rest, only ion channels for potassium are open at the plasma membrane, through which other ions cannot pass.

Leaving the cell, potassium cations reduce the number of positive charges in it and at the same time increase their amount on the outer surface of the membrane. The organic anions remaining in the cell begin to restrict the further release of potassium cations, since an electric field arises between the anions of the inner surface of the membrane and the cations of its outer surface and appears electrostatic attraction... The cell membrane itself turns out to be polarized: positive charges are grouped on its outer surface, and negative charges on the inner surface.

Thus, if the membrane is ready to pass any ions, then the direction of the ion current will be determined by two circumstances: the concentration gradient and the action of the electric field, and the concentration gradient can direct the ions in one direction, and the electric field in the other. When these two forces are balanced, the flow of ions practically stops, since the number of ions entering the cell becomes equal to the number of ions leaving. This state is called equilibrium potential.

Active transport T

Diffusion of ions should decrease the concentration gradient, but concentration equilibrium would mean death for the cell. It is no coincidence that it spends more than 1/3 of its energy resources on maintaining gradients, on maintaining ionic asymmetry. The transport of ions across the cell membrane against concentration gradients is active, i.e. energy-consuming mode of transport, it is provided by a sodium-potassium pump.

It is a large integral protein of the cell membrane that continuously removes sodium ions from the cell and simultaneously pumps potassium ions into it. This protein has the properties of ATPase, an enzyme that breaks down ATP on the inner surface of the membrane, where the protein attaches three sodium ions. The energy released during the cleavage of the ATP molecule is used to phosphorylate certain areas of the pump protein, after which the protein conformation changes and it removes three sodium ions from the cell, but at the same time takes two potassium ions from the outside and introduces into the cell (Fig. 4.1).

Thus, in one cycle of the pump operation, three sodium ions are removed from the cell, two potassium ions are introduced into it, and the energy of one ATP molecule is spent on this work. This is how a high concentration of potassium in the cell is maintained, and sodium in the extracellular space. Considering that both sodium and potassium are cations, i.e. carry positive charges, the total result of one pump cycle for the distribution of electric charges is the removal of one positive charge from the cell. As a result of this activity, the membrane becomes a little more negative from the inside and therefore the sodium-potassium pump can be considered electrogenic.

In 1 second, the pump is capable of removing about 200 sodium ions from the cell and simultaneously transferring about 130 potassium ions into the cell, and one square micrometer of the membrane surface can accommodate 100-200 such pumps. In addition to sodium and potassium, the pump transports glucose and amino acids into the cell against concentration gradients; this, as it were, passing transport, got the name: simport. The performance of the sodium-potassium pump depends on the concentration of sodium ions in the cell: the more it is, the faster the pump works. If the concentration of sodium ions in the cell decreases, then the pump will also decrease its activity.

Along with the sodium-potassium pump in the cell membrane, there are special pumps for calcium ions. They also use the energy of ATP to remove calcium ions from the cell, as a result of which a significant concentration gradient of calcium is created: there is much more of it outside the cell than in the cell. This makes calcium ions constantly strive to enter the cell, but at rest, the cell membrane almost does not allow these ions to pass through. However, sometimes the membrane opens channels for these ions and then they play a very important role in the release of mediators or in the activation of certain enzymes.

Thus, active transport creates concentration and electrical gradients which play an outstanding role in the entire life of the cell.

Subject table of contents "Endocytosis. Exocytosis. Regulation of cellular functions.":
1. Influence of the Na / K-pump (sodium potassium pump) on the membrane potential and cell volume. Constant cell volume.

3. Endocytosis. Exocytosis.
4. Diffusion in the transport of substances inside the cell. The importance of diffusion in endocytosis and exocytosis.
5. Active transport in organelle membranes.
6. Transport in the vesicles of the cell.
7. Transport through the formation and destruction of organelles. Microfilaments.
8. Microtubules. Active movements of the cytoskeleton.
9. Axon transport. Fast axonal transport. Slow axonal transport.
10. Regulation of cellular functions. Regulatory effects on the cell membrane. Membrane potential.
11. Extracellular regulatory substances. Synaptic mediators. Local chemical agents (histamine, growth factor, hormones, antigens).
12. Intracellular communication with the participation of second mediators. Calcium.
13. Cyclic adenosine monophosphate, cAMP. cAMP in the regulation of cell function.
14. Inositol phosphate "IF3". Inositol triphosphate. Diacylglycerol.

Meaning Na / K-pump for cell is not limited to stabilization of normal K + and Na + gradients on the membrane. The energy stored in the Na + membrane gradient is often used to provide membrane transport of other substances. For example, in Fig. 1.10 shows the "symport" of Na + and sugar molecules into the cell. Membrane transport protein transfers the sugar molecule into the cell even against the concentration gradient, at the same time Na + moves along the gradient of concentration and potential providing energy for the transport of the Sugars. Such transport of the Sakharov completely depends on the existence high sodium gradient I am; if the intracellular sodium concentration increases significantly, then the transport of sugars stops.

Rice. 1.8. The ratio between the rate of transport of molecules and their concentration (at the point of entry into the channel or at the point of binding of the pump) during diffusion through the channel or during pumping transport. The latter is saturated at high concentrations (maximum speed, V max); the value on the abscissa, corresponding to half the maximum pump speed (Vmax / 2), is the equilibrium concentration Kt

There are different flavor systems for different sugars. Transport of amino acids into the cell is similar to the transport of sugars shown in Fig. 1.10; it is also provided with a Na + gradient; there are at least five different systems symptoms, each of which is specialized for any one group of related amino acids.

Rice. 1.10. Proteins immersed in the lipid bilayer of the membrane mediate the symptoms of glucose and Na in the cell, as well as the Ca / Na antiport, in which the Na gradient on the cell membrane is the driving force.

In addition to Symport systems there are also “ antiport". One of them, for example, transfers one calcium ion from the cell in one cycle in exchange for three incoming sodium ions (Fig. 1.10). Energy for the transport of Ca2 + is formed due to the entry of three sodium ions along the concentration and potential gradient. This energy is sufficient (at resting potential) to maintain a high gradient of calcium ions (from less than 10 -7 mol / L inside the cell to about 2 mmol / L outside the cell).

Dx - concentration gradient,

T - absolute temperature

M mol

Jm = ––- ––––(–- ––––); m - amount of substance

S × t m s Jm - (jay) – substance flux density.

Electrochemical potential–- value equal to energy Gibbs G for one mole of a given substance, placed in an electric field.

Gibbs free energy (or simply Gibbs energy, or Gibbs potential, or thermodynamic potential in a narrow sense) is a quantity that shows the change in energy during a chemical reaction and thus gives an answer to the question of the fundamental possibility of a chemical reaction; this is the thermodynamic potential of the following form:

G = U + PV–TS

where U is internal energy, P is pressure, V is volume, T is absolute temperature, S is entropy.

(Thermodynamic entropy S, often simply called entropy, in chemistry and thermodynamics is a function of the state of a thermodynamic system)

Gibbs energy can be understood as the total chemical energy of a system (crystal, liquid, etc.)

The concept of Gibbs energy is widely used in thermodynamics and chemistry.

Thermodynamic entropy S, often simply called entropy, in chemistry and thermodynamics is a function of the state of a thermodynamic system.

For dilute solutions, the substance flux density is determined by the Nernst-Planck equation.

d × C d × φ

Jm =–U × R × T––––- –U × C × Z × F––––- ;

d × x d × x

U–particle mobility,

R - gas constant 8.31 J / mol,

z–electrolyte ion charge,

F-Faraday number 96500 kg / mol,

dφ is the potential of the electric field,

dφ

There are two reasons for the transfer of matter during passive transport: concentration gradient and electric potential gradient... (Minus signs in front of the gradient indicate that the concentration gradient causes the substance to transfer from places of higher concentration to places of lower concentration). The gradient of electrical potential causes the transfer of positive charges from places with a large to places with a lower potential.

Passive transfer of substances from places with a lower concentration to places with a higher concentration can occur (if the second term of the equation is greater in modulus than the first).

If not electrolytes Z = 0; or there is no electric field, then simple diffusion occurs - Fick's law.

Jm =–- D ×––––;

D is the diffusion coefficient;

- –- ––– concentration gradient;

Diffusion - spontaneous movement of substances from places with a higher concentration to places with a lower concentration of a substance, due to the chaotic thermal movement of molecules.

Diffusion of a substance through a lipid bilayer is caused by a concentration gradient in the membrane. The membrane permeability coefficient depends on the properties of the membrane and the substances carried. (If the concentration of the substance at the surface in the membrane is directly proportional to the concentration at the surface outside the membrane).

P = -–- ––- – permeability coefficient

K–distribution coefficient, which shows the ratio of the concentration of a substance outside the membrane and inside it.

L–membrane thickness;

D is the diffusion coefficient;

Coefficient the higher the diffusion coefficient (the lower the membrane viscosity), the thinner the membrane and the better the substance dissolves in the membrane, the greater the permeability.

Non-polar substances - organic fatty acids, poorly - polar water-soluble substances - salts, bases, sugars, amino acids - penetrate well through the membrane.

With thermal movement, small free planes are formed between the tails - they are called blades through which polar molecules can penetrate. The larger the size of the molecule, the lower the membrane permeability for this substance. The selectivity of transfer is ensured by a set of pores of a certain radius in the membrane corresponding to the size of the penetrating particle.

Facilitated diffusion- occurs with the participation of carrier molecules. The carrier of potassium ions is valinomycin, which is shaped like a cuff; covered inside with polar groups, and outside with non-polar groups. High selectivity is characteristic. Valinomycin forms a complex with potassium ions, which get inside the cuff, and it is also soluble in the lipid phase of the membrane, since its molecule is non-polar outside.

Valinomycin molecules at the membrane surface capture potassium ions and transport it across the membrane. Transfer can occur in both directions.

Facilitated diffusion occurs from places with a higher concentration of the carried substance to places with a lower concentration.

Differences between easy diffusion and simple:

1) the transfer of the substance with the carrier is faster.

2) Facilitated diffusion has the property of saturation, with an increase in concentration on one side of the membrane, the flux density increases until all carrier molecules are occupied

3) With facilitated diffusion, there is competition between the transferred substances, when different substances are transferred by the carrier; however, some substances are better tolerated than others, and the addition of some substances hinders the transport of others. Thus, glucose is better tolerated from sugars than fructose, fructose is better than xylose, and xylose is better than arabinose.

4) There are substances that block facilitated diffusion - they form a strong complex with carrier molecules. Immobile molecules - carriers fixed across the membrane are transferred from molecule to molecule.

Filtration- the movement of the solution through the pores in the membrane under the action of a pressure gradient. The transfer rate during filtration obeys Poiseuille's law.

D v P1 - P2

–- –– = - ––––––;

In order to understand how and why excitation occurs in nerve or muscle cells, it is first of all necessary to understand the basic rules of the exchange of substances between the cell and its environment, since ions and small molecules are simultaneously dissolved in the aqueous medium of the cell and in the extracellular space, where their concentration differs from the intracellular one. It is sometimes said among biologists that God created an ideal organism to study any biological problem. The experiments underlying the membrane theory were carried out in the 40s of the twentieth century on giant squid axons.

The diameter of these axons reaches 1 mm, they can be seen even with the naked eye, it is easy to insert electrodes into them in order to investigate the occurrence of electrical signals - action potentials. It was on such an object that the founders of the membrane theory, British physiologists Alan Hodgkin and Andrew Huxley (Hodgkin A., Huxley A.), the 1963 Nobel Prize winners, worked. The cytoplasm of squid giant axons differs from the surrounding extracellular fluid in the concentration of certain ions (Table 4.1).

Equilibrium potential is such a value of the transmembrane difference in electric charges, at which the current of ions in and out of the cell becomes the same, i.e., in fact, the ions do not move.

As can be seen from the table, the concentration of potassium ions inside the cell is much higher than in the extracellular fluid, while the concentration of sodium and chlorine ions, on the contrary, is much higher in the extracellular fluid. Organic anions are large molecules that do not pass through the cell membrane.

Is it correct or not to draw any conclusions about the cell membranes of warm-blooded animals, especially humans, when studying the nerve cells of squid? Let us compare their giant axons, for example, with the muscle cells of warm-blooded animals (Table 4.2).

The results of measurements of ion concentrations in different cells of animals belonging to different species give, of course, different values of these concentrations, but one thing is common for all cells, in all animal species: the concentration of potassium ions is always higher in the cell, and the concentration of sodium and chlorine ions - in the extracellular fluid.

This concentration difference or concentration gradient is the driving force for the diffusion of dissolved ions to a region of lower concentration or, in accordance with the second law of thermodynamics, to a lower energy level. Looking again at the numbers presented in the tables, one can accurately predict that sodium cations should diffuse into the cell, and potassium cations - from it.

However, not everything is so simple, since it is necessary to take into account the permeability of the cell membrane for various ions, and it changes depending on the state of cell activity. At rest, only ion channels for potassium are open at the plasma membrane, through which other ions cannot pass. Does this mean that potassium ions can escape freely through the membrane of a resting cell?

Leaving the cell, potassium cations reduce the number of positive charges in it and at the same time increase their amount on the outer surface of the membrane. The organic anions remaining in the cell begin to restrict the further release of potassium cations, since an electric field arises between the anions of the inner surface of the membrane and the cations of its outer surface and an electrostatic attraction appears. The cell membrane itself turns out to be polarized: positive charges are grouped on its outer surface, and negative charges on the inner surface.

where R is the gas constant, T is the absolute temperature (310 at body temperature), z is the ion valence (for potassium = 1), F is the Faraday constant, a is the concentration of potassium ions outside the cell, [K] i is the concentration of potassium ions in cage.

If we substitute the value of the constants and the concentration of ions into the equation, then the equilibrium potential of the membrane of the squid axon for potassium ions will be equal to - 75 mV (for the muscle membrane of warm-blooded animals - -97 mV). This means that with such a transmembrane potential difference and with such values of the intra- and extracellular concentration of potassium ions, their current from the cell becomes equal to the current into the cell. If the transmembrane potential difference becomes smaller, then potassium ions will leave the cell until the value of the equilibrium potential is restored.

In resting glial cells, the membrane allows only potassium ions to pass through; therefore, the real transmembrane potential difference in them coincides with the calculated one, i.e., with the value of the equilibrium potential for potassium - 75 mV. But in most neurons, the situation is different, since their membrane at rest passes not only potassium ions, but also sodium and chlorine ions in small quantities. In this regard, the transmembrane potential difference turns out to be somewhat less than the equilibrium potassium potential, but insignificantly, since the permeability for potassium ions at rest is much higher than for sodium and chlorine ions.

Using the Nernst equation, it is easy to find the value of the equilibrium potentials for any ions (for sodium and chlorine, they are given in Table 1). The equilibrium potential for sodium is + 55 mV, and its concentration in the extracellular medium is much higher than in the cell; both induce sodium ions to enter the cell. But at rest, the cell membrane does not give them this opportunity: its permeability to sodium ions is extremely low.

Diffusion of ions should decrease the concentration gradient, but concentration equilibrium would mean death for the cell. It is no coincidence that it spends more than 1/3 of its energy resources on maintaining gradients, on maintaining ionic asymmetry. The transport of ions across the cell membrane against concentration gradients is an active, i.e., energy-consuming mode of transport, it is provided by a sodium-potassium pump.

It is a large integral protein of the cell membrane that continuously removes sodium ions from the cell and simultaneously pumps potassium ions into it. This protein has the properties of ATPase, an enzyme that breaks down ATP on the inner surface of the membrane, where the protein attaches three sodium ions. The energy released during the cleavage of the ATP molecule is used to phosphorylate certain parts of the pump protein, after which the protein conformation changes and it removes three sodium ions from the cell, but at the same time takes two potassium ions from the outside and introduces into the cell (Fig. 4.1).

Thus, in one cycle of the pump operation, three sodium ions are removed from the cell, two potassium ions are introduced into it, and the energy of one ATP molecule is spent on this work. This is how a high concentration of potassium in the cell is maintained, and sodium in the extracellular space. If we take into account that both sodium and potassium are cations, that is, they carry positive charges, then the total result of one pump cycle for the distribution of electric charges is the removal of one positive charge from the cell. As a result of this activity, the membrane becomes a little more negative from the inside and therefore the sodium-potassium pump can be considered electrogenic.

Thus, active transport creates concentration and electrical gradients that play a prominent role throughout the life of the cell.

4.3. Passive transport - diffusion

The gradients created by the operation of the pumps allow ions to move through the membrane from a higher energy level to a lower one by diffusion, if, of course, there are open ion channels. Such a channel is a large-molecular integral protein, the molecule of which passes through a double layer of membrane lipids. This molecule has a pore filled with water, the diameter of which does not exceed 1 nm. Only potassium ions can pass through such a hole (Fig. 4.2).

The radius of the potassium ion is 0.133 nm, for the sodium ion it is even less - 0.098 nm, however, only potassium can pass through the constantly open channels. The fact is that the true dimensions of an ion are determined by the thickness of its hydration shell, which covers all ions in an aqueous solution. Water molecules behave like dipoles: the electrons of their oxygen atoms are stronger than those of hydrogen atoms, which means that oxygen carries a weak negative charge. That is why water molecules are attracted by the positive charges of potassium, sodium and calcium cations. But, since the hydrogen atoms in the water molecule have a weak positive charge, there is an attraction of water molecules to the chlorine anions.

At a smaller ionic radius, the electric field of the sodium ion is stronger than that of potassium, and therefore its hydration shell is thicker. It does not allow sodium ions to pass through channels that are accessible for the passage of potassium alone. That is why, in the state of rest of the cell membrane, a current of mainly one type of ions occurs through it - potassium, constantly leaving the cell along the concentration gradient.

The channels just described through which potassium ions pass are always open: both at rest and during cell excitation - they depend little on external conditions and therefore are passive channels. In contrast, there are controlled ion channels, most of which are closed cells at rest, and in order to open them, you need to somehow act on them. Consequently, such channels are controllable, and depending on the control method, they are divided into three types:

1) potential-dependent;

2) chemically dependent;

3) mechanically driven.

The device by which the channels are opened or closed is often called a gate mechanism or even a gate, although this comparison is not entirely correct. Modern concepts of ion channels have developed in connection with two methodological approaches to their study. Firstly, it is the patch clamp method, which allows observing the ion current through a single channel. This technique was invented in the late 70s by Erwin E., Sakmann B., 1991 Nobel Prize winners. Second, the understanding of the properties of the channels was facilitated by the construction of their models on the basis of the decoded genetic code of many channel proteins and the amino acid sequence of molecules established in connection with this.

Each channel is formed by several protein subunits (Fig. 4.3), which are long chains of amino acids twisted into an a-helix. The shape of the a-helix can change, for example, due to a change in the transmembrane potential difference (which is extremely important for voltage-gated channels).

The change in the shape of the a-helix leads to the movement of amino acids, including those carrying an electric charge. As a result, the charges of amino acids such as lysine or arginine can end up in the inner wall of the ion channel and make it hydrophilic: then ions covered with a hydration shell can pass through the channel. The return of the alpha-helix to its previous shape leads to the fact that hydrophobic areas again appear in the inner wall of the channel and therefore the ion flow stops.

In the formation of different types of channels, from two to seven subunits are involved, the protein chain of each subunit crosses the cell membrane several times, and each area of intersection performs a specific task: some form the channel walls, others serve as sensors for changes in the electric field, and others protruding beyond the outer side of the membrane, are receptors, the fourth combine the channel with the cytoskeleton.

Potentially gated channels are opened or closed due to certain changes membrane potential... For example, sodium channels are closed at rest, but if the membrane potential decreases to a critical value, they open. If depolarization continues to a positive value of the membrane potential (i.e., there will be more positive charges on the inside of the membrane than on the outside), then the channels will close.

Chemically dependent channels open due to the attachment of a neurotransmitter to the protruding glycoprotein receptor region of the channel protein - this type of channel is used in synapses (Fig. 4.4). Mechanically controlled channels are characteristic of the sensitive endings of neurons that respond to tension and pressure. These channels are connected in a special way with the cytoskeleton, which leads to their opening when the cell is deformed.

The very moment the channel opens is just an instant lasting in millionths of a second. But even in the open state, the channels are not for long - only a few milliseconds, after which they rapidly close. However, the throughput of the open channel is amazing: the flow of ions occurs at a speed of up to 100,000,000 ions / s, which can only be compared with the activity of the fastest enzymes, such as carbonic anhydrase, which catalyzes the formation and dehydration of carbon dioxide in erythrocytes.

In addition to open and closed conformational states, channels can become inactivated: this means that they are closed, but do not obey, as usual, the action of control mechanisms and do not open. The state of inactivation is observed immediately after the closure of the channels, lasts several ms and is controlled by special subunits or special regions of the protein molecule. During the inactivation of the channels, the cell ceases to respond to the stimuli that excite it, which is defined by the term refractoriness, that is, temporary non-excitability.

Ionic channels are present in the membrane of any cell of the body, but in muscle and especially in nerve cells, their density is much higher than in the cells of other tissues. In neurons, in addition to a high density of channels, a wide variety of them was also found. This is not accidental, since it is the channels that determine the conditions for the appearance of electrical signals, the nature of the signals themselves, the speed of their conduction, etc., which actually allows neurons to perform their main task: to receive, process and transmit information.

4.5. Ion channel blockers

There are quite a few substances that can reversibly or irreversibly bind to molecules of channel proteins and, thereby, block them, that is, remove them from subordination to control mechanisms. Blocked channels most often turn out to be closed, although in some cases the open position of the channel is fixed.

Many of the long-known poisons of animal or vegetable origin are capable of blocking the channels. So, for example, in the insides of some joint-jawed fish (Tetrodontiformes) contains tetrodotoxin, which blocks sodium channels. This group includes the notorious puffer fish, which claimed the lives of many gourmets, as well as the dog-fish swimming in the waters of the Peter the Great Bay, capable of swelling and making rather loud sounds. Tetrodotoxin has been used for a long time in experimental practice related to the study of membrane permeability.

Sodium channels can also be blocked by another animal poison - batrachotoxin, which is contained in the mucus of some South American frogs, for example, the spotted poison dart frog. The Indians poisoned their arrows with this poison, although they did not realize that batrachotoxin blocks sodium channels, and such a blockade does not allow nerve cells to be excited.

Other South American Indians prepared poisoned arrows with another poison, vegetable - this is the tree sap of curare, obtained from some species of vines. The curare venom selectively blocks the chemodependent channels of the neuromuscular synapses. The same synapses are irreversibly blocked by the snake venom alpha-bungarotoxin, which is secreted by the bite of bungars, they are also krait - close relatives of cobras.

Substance of artificial origin - tetraethylammonium specifically blocks potassium channels; it was often used in experimental practice. And in medicine, many are used medicinal substances, the point of application of which are ion channels: with the help of such substances, it is possible to control certain ion channels and thereby influence the activity of neurons.

At rest, a thin layer of positive charges is located on the outer side of the plasma membrane, and negative charges on the inner side. The electric charge of the outer surface is considered to be zero; therefore, the transmembrane potential difference or the resting membrane potential has a negative value. In a typical case for most neurons, the resting potential is approximately -60 - -70 mV.

The technique of direct measurement of the resting potential was created in the late 1940s. A special measuring electrode was made: a thin glass capillary with a drawn-off tip, no more than 1 μm in diameter, and filled with an electrically conductive saline solution (3M KCl). which does not change the internal charge of the membrane. A metal conductor was inserted into this solution from the wide end of the capillary, and the cell membrane was pierced with the thin end. The second electrode was a chlorinated silver plate and was placed in the external environment; an amplifier of weak electrical signals and a galvanometer were used (Fig. 4.5). The object of the study was a giant squid axon, it was on it that data were obtained that served as the basis for the membrane theory (Hodgkin Huxley).

How does the resting membrane potential arise? Before answering this question, it should be reminded once again that the work of the sodium-potassium pump in the cell creates a high concentration of potassium ions, and there are open channels in the cell membrane for these ions. Potassium ions leaving the cell along the concentration gradient increase the amount of positive charges on the outer surface of the membrane. There are many large-molecular organic anions in the cell, and therefore the membrane is negatively charged from the inside. All other ions can pass through the resting membrane in a very small amount, their channels are mostly closed. Consequently, the resting potential owes its origin mainly to the current of potassium ions from the cell.

This conclusion is easy enough to verify experimentally. If, for example, the concentration of potassium ions around the cell is artificially increased, then their current from the cell will decrease or even stop altogether, since the concentration gradient, which is the driving force for this current, will decrease. And then the resting potential will begin to decrease, it can become equal to zero if the potassium concentration on both sides of the membrane turns out to be the same. There is one more opportunity to prove the potassium nature of the resting potential. If the potassium channels are blocked with tetraethylammonium, the flow of potassium ions will stop, and after that the resting potential will begin to decrease.

The membrane of a resting cell passes in a small amount of sodium and chlorine ions. Two forces drive sodium ions into the cell: a high external concentration and an electronegative internal cell environment. Even a small amount of sodium that has entered the cell leads to membrane depolarization - a decrease in the resting potential. It is more difficult for chlorine ions to enter the cell, since they are repelled by the electronegative layer of charges on the inner surface of the membrane, and the value of the equilibrium potential of chlorine -60 mV differs little from the normal value of the resting potential. The relationship between the selective membrane permeability for each of the three types of ions and their concentrations is described by the Goldmann equation:

where E m is the value of the membrane potential, P is the membrane permeability, depending on its thickness and the mobility of the ion in it, a is the concentration of the ion outside, i is its concentration from the inside, R, T and F have the same meaning as in the Nernst equation ...

It follows from this equation that the real value of the resting potential (Em = - 65 mV) is a compromise between the equilibrium potentials of potassium (- 75 mV), sodium (+ 55 mV) and chlorine (- 60 mV). It is easy to predict that an increase in the permeability of the membrane to sodium will lead to depolarization, and an increase in its permeability to chlorine will lead to hyperpolarization.

If we take the permeability of the membrane at rest for potassium ions as 1, then its permeability for sodium ions will be 0.04, and for chlorine - 0.45. But when the membrane is excited, this ratio changes and at the top of the peak of the action potential is 1 (K): 20 (Na): 0.45 (Cl).

Goldman's equation allows you to calculate the value of the resting membrane potential if the concentration of ions inside the cell and outside, as well as the permeability for these ions, is known. The real value of the resting membrane potential is closest to the value of the equilibrium potential for potassium ions, which pass through channels constantly open for them. The situation changes drastically when the cell is irritated, when sodium permeability increases and a depolarizing receptor potential or postsynaptic potential appears.

An action potential arises only at a certain value of the depolarizing shift, for example, from -65 mV to -55 mV. If the depolarization is less, then the action potential will not arise: such depolarizing shifts are called subthreshold. The numbers given here are relative, in different cells they can be less or more, but always the smallest depolarizing shift that will cause the appearance of an action potential is defined as a threshold one.

The emergence of receptor or postsynaptic potentials is associated with a relatively small local increase in the sodium permeability of the membrane. The entry of sodium ions into the cell and the resulting local depolarization lead to a local electric current. Its propagation along the membrane is prevented by the electrical resistance of the membrane itself, therefore, the passive depolarization that has begun in some place cannot spread far - passive electrical responses are always local.

But, if the sum of local depolarizing shifts can still depolarize the membrane of the trigger zone of the neuron to critical level, up to the threshold value, then an active and maximum response of the cell according to the "all or nothing" rule will occur. Depolarization to a critical value leads to conformational changes in the inner wall of sodium channels and the movement of polar amino acids. As a result, a pore with a diameter of 0.3 - 0.5 nm opens through which sodium cations can pass (see Fig. 4.3). The flow of anions through this channel is impossible, since its mouth contains negative charges of the carboxyl groups of glutamic acid, which repel the negative charges of the anions.

The equilibrium sodium potential is +55 mV, and the channels for it open at a membrane potential of -55 mV, so sodium ions enter the cell at a high rate: up to 107 ions / s through a single channel. The density of sodium channels varies from 1 to 50 per square micrometer. As a result, in 0.2-0.5 ms, the value of the membrane potential from negative (-55 mV) becomes positive (about +30 mV), although it does not reach the value of the equilibrium sodium potential.

Such rapid depolarization is self-regenerating: the more sodium enters the cell and the greater the shift of the membrane potential, the more sodium channels open and then even more sodium enters the cell:

As the value of the membrane potential approaches the value of the equilibrium sodium potential, the driving force for sodium ions weakens, but at the same time the driving force grows, forcing potassium ions to leave the cell, the channels for which are constantly open. When the membrane potential becomes positive, the voltage-gated sodium channels are closed, and the potassium flow from the cell increases dramatically. In this regard, repolarization occurs, that is, the restoration of the initial value of the membrane potential (sometimes the output current of potassium leads even to a short-term trace hyperpolarization). The two phases of the action potential — depolarization and repolarization — form a peak or spike in the action potential (Fig. 4.6).

The very opening of sodium channels occurs unusually quickly, within no more than 10 microseconds (i.e., millionths of a second), they remain open for several milliseconds, then quickly close, and for some time the conformation of the channel protein becomes such that it cannot be activated , and hence open channels. This state is called refractoriness, about 1 ms it is absolute, and then relative: with absolute refractoriness, the channels cannot be opened by any action, with relative they cannot be activated by threshold depolarization, but they can be above-threshold.

The total duration of the refractory state determines the maximum frequency of neuron excitation. For example, if the refractory period lasts 2 ms, then in 1 s the neuron can be fired a maximum of 500 times (1 s = 1000 ms: 2 ms = 500). Some neurons can be fired more often than 500 / s, others less often: in accordance with this, the former can be called more labile than the latter. The problem of lability or functional mobility of cells in the late 19th - early 20th centuries was investigated by the Russian physiologist N.E. Vvedensky, who also introduced the concept of the measure of lability as the largest number of electrical oscillations that a nerve or muscle can reproduce in a second. So, for example, a nerve, according to Vvedensky's data, is capable of being excited up to 500 / s, and a muscle only up to 200 / s, that is, a nerve is a more labile object than a muscle.

The more complex problems the brain solves, the large quantity neurons he needs. However, the entire mass of neurons must fit in the space limited by the skull and the spinal canal, and therefore the nerve cells must be small, and their processes must be thin enough. But, as you know, the thinner and longer the conductor, the more resistance it will have to the current propagating through it. The effective voltage in the neuron (V) cannot be greater than the amplitude of the action potential, i.e. approximately 100-120 mV, and the current (I), according to Ohm's law, is directly proportional to the voltage and inversely proportional to the resistance: I = V / R

It follows from this that the action potential in the usual way for conducting electricity cannot spread far. The very thin membrane of the axon, surrounded by an electrically conductive medium, has a very high capacitance, which inhibits the propagation of an electrical signal. To put it simply: a thin cytoplasmic process is a very poor conductor. But, despite this, action potentials propagate along the axon at a high speed, reaching 100 m / s. How does this happen?

When sodium permeability increases in the excited area of the membrane and an action potential arises, the electrotonic propagation of positive charges to the unexcited area begins - this process is a circular current (Fig. 4.7). Such a current depolarizes the not yet excited neighboring area, and when this depolarization reaches the threshold, an action potential arises. Now this area becomes a source of circular current acting on the next area of the membrane, now in this area an action potential will arise, all the parameters of which will be standard for this type of neuron.

Following an increase in sodium permeability during the formation of an action potential, the potassium flow from the cell increases. Together with potassium, positive charges leave the cell and the previous value of the membrane potential is restored. For any length of the axon, the amplitude of the action potentials is the same everywhere, since in each separate section of the axon they are actually formed anew. In a physiological sense, this is important because the constancy of the signal means the transmission of information along the axon without distortion.

In myelinated axons, the circular current spreads to the adjacent intercept, where the action potential arises. The density of sodium channels in Ranvier's interceptions is much higher than in a conventional unmyelinated membrane, and the circular current that comes here electrotonically easily depolarizes the interception to a threshold value. The resulting action potential serves as a source of circular current for the next interception.

The conduction of excitation in a nerve or muscle can be recorded using extracellular electrodes applied to two different points on their surface and connected to the recording equipment. When the action potential propagates, the membrane alternately depolarizes, first under the electrode closest to the excitation source, and then under the far one. In both cases, a potential difference is recorded between the electrodes, since one of them will be located in a depolarized, and therefore electronegative, area outside the membrane, and the second - in an intact electropositive point, where the excitation has not yet begun, or has already ended.

Registration of action potentials passing through the membrane using two electrodes is called bipolar. With this method, two phases of the action potential are recorded: positive and negative. If the area under one of the electrodes is made non-excitable (for this you can act on it with some anesthetic, for example, novocaine), then only one phase of the action potential will remain. This lead is called unipolar (or monopolar).

In some autoimmune and viral diseases, the myelin sheath is destroyed, which leads to numerous neurological disorders, up to the complete loss of some functions; in this case, both emotional activity and intelligence can be disrupted. Multiple sclerosis is an example of a demyelinating disease.

Summary

The appearance of electrical signals is associated with the properties of the cell membrane. Diaphragm pumps create ion concentration gradients. The ion channels open at rest for potassium allow it to leave the cell and, thereby, create a resting membrane potential close to the equilibrium potential for potassium. In the case of its decrease to the threshold value, voltage-dependent channels for sodium open and self-regenerating depolarization occurs, the value of the membrane potential becomes positive, This causes the closure of sodium channels, which are temporarily inactivated. The outgoing current of potassium ions restores the previous value of the membrane potential. The emergence of an action potential causes the appearance of a circular electric current, which depolarizes the adjacent portion of the membrane to a threshold value. In this regard, the action potential spreads along the axon without decreasing the amplitude.

Questions for self-control

46. The concentration of which ions in the cell is much higher than in the extracellular fluid?

A. Sodium; B. Potassium; B. Calcium; G. Chlorine; D. Magnesium.

47. What ion channels are open during physiological rest of the cell?

A. For all cations; B. For anions; B. For sodium; G. For potassium; B. For calcium.

48. What is the value of the equilibrium potential of the membrane of the giant squid axon for potassium ions?

A. +55 mV; B. + 25-30 mV; B. = 0; G. -60 mV; D. -75 mV.

49. Why is the sodium-potassium pump considered electrogenic?

A. It consumes the energy of ATP; B. It creates a potassium concentration gradient; C. It removes sodium from the cell; D. In one cycle, it removes a positive charge from the cell; D. It provides the sympathy of glucose and amino acids.

50. What ions are prevented from entering the cell by the electric field between the inner and outer surfaces of the membrane?

A. Potassium; B. Sodium; B. Chlorine; G. Calcium; D. All cations.

51. Through what type of channels do potassium ions diffuse when the cell is in a state of physiological rest?

A. Potential dependent; B. Chemically dependent; B. Potential and chemically dependent; D. Mechanically operated; D. Passive.

52. Which of the following is characteristic of the refractory state?

A. Activated state of voltage-gated channels; B. Inactivated state of voltage-gated channels; B. Open state of voltage-gated channels; D. Closed state of voltage-gated channels; D. Increasing the capacity of voltage-dependent channels.

53. Which of the following substances is a blocker ion channels for potassium?

A. Tetraethylammonium; B. Tetrodotoxin; B. Batrachotoxin; G. Kurare; D. a-Bungarotoxin.

54. What should be the smallest depolarizing shift if the membrane potential is -69 mV, and the critical depolarization level is -56 mV?

A. 6 mV; B. 9 mV; V. 11 mV; G. 13 mV; D. 15 mV.

55. If the refractory period of a neuron lasts 3 ms, then with what maximum frequency can it be excited?

A. 555 Hz; B. 444 Hz; V. 333 Hz; G. 222 Hz; D. 111 Hz.

56. For what movement of ions through the cell membrane, which is at rest of the cell, energy is needed?

A. Calcium in the cell; B. Sodium in the cell; B. Chlorine in the cage; D. Potassium from the cell; D. Calcium from the cell.

57. What movement of ions occurs only through diffusion?

A. Sodium from the cell; B. Potassium from the cell; B. Calcium from the cell; G. Potassium in the cage; D. Glucose into the cell.

58. What makes the voltage-dependent channels for sodium that open upon excitation to close?

A. Repolarization process; B. Restoration of the initial value of the membrane potential; B. Establishing a positive value of the membrane potential; D. Achieving a critical level of depolarization; D. The emergence of hyperpolarization.

59. What are the consequences of an increase in membrane permeability for chlorine at a real membrane potential of -55 mV?

A. Decrease in membrane potential; B. Hyperpolarization; B. Depolarization; D. The value of the membrane potential will not change; E. An action potential will arise.

60. Each action potential is formed by two, successively replacing each other phases - these are:

A. Hyperpolarization-depolarization; B. Depolarization-repolarization; B. Hyperpolarization-repolarization; D. Repolarization - depolarization; E. Repolarization - restoration of the initial value of the membrane potential.

Hello! By definition, the concentration gradient is directed from the side of the lower concentration to the side of the larger one. Therefore, diffusion is always said to be directed against the concentration gradient, i.e. from the side with more concentration to the side with less concentration.
However, when you read the literature about the vital activity of a cell, photosynthesis, it always says that "along the concentration gradient" is in the direction of decreasing concentration, and "against the concentration gradient" - in the direction of increasing concentration, and thus, for example, simple diffusion into cells (or, in other words, ordinary diffusion) is directed along the concentration gradient.
But a contradiction arises. It turns out that the expression "along the concentration gradient" is actually a movement opposite to the direction of the concentration gradient. How can this be?

This persistent and widespread error is associated with the difference in the understanding of the direction of the concentration gradient vector in physics and biology. Biologists prefer to talk about the direction of the concentration gradient vector from higher to lower values, and physicists from lower to higher values.