There is more sodium or potassium in the cell. Changes in extracellular potassium concentration (K)

The mineral composition of cells differs sharply from the mineral composition of the external environment. In the cell, as a rule, the concentration of potassium, magnesium and phosphorus ions predominates, and in the environment - sodium and chlorine. This can be clearly seen from the data presented in Table 7.

Inside the cell, minerals are also distributed unevenly between the cytoplasm, its organelles and the nucleus. Thus, the sodium concentration in the nucleus of frog eggs is three times higher than in the cytoplasm, and potassium is twice as high (Table 8).

Mitochondria are also capable of accumulating potassium and especially calcium. Its concentration in isolated mitochondria can exceed the calcium concentration in the surrounding saline solution by 3500 times. This uneven distribution is explained by the fact that these substances in the nucleus and mitochondria are partially bound.

Salt asymmetry depends on the functional state of the cell, and with the death of the cell it is lost, i.e. the salt content in the cell and the environment is equalized. The isolation of cells and tissues from the body is usually accompanied by a slight loss of potassium and an increase in sodium.

Rice. 25. Dependence of the concentration of sodium and chlorine ions in muscle fibers on their concentration in the medium, meq% (Fenn, Cobb and Marsh, 1934–1935)

When the concentration of sodium and chlorine ions in the medium changes, their content in the cells changes in direct proportion (Fig. 25). For many other ions (K+, Ca2+, Mg2+, etc.) proportionality is not observed. The dependence of the concentration of potassium in the muscles of the frog on its concentration in the environment is shown in Figure 26.

Rice. 26. Dependence of the concentration of potassium ions in frog muscles (C avg, meq per 100 g of muscle) on their concentration in the medium (C avg, meq %)

Almost all mineral ions penetrate into cells, albeit at very different rates. Using the isotope technique, it was shown that there is a constant exchange of cell ions for environmental ions and with a stationary (unchanging) distribution. In this case, the magnitude of the ion flow inward is equal to its flow in the opposite direction. Ion fluxes are usually expressed in picomoles (1 pmol equals 10-12 M). Table 9 shows the fluxes of potassium and sodium ions into the cell for different objects. Mineral ions penetrate faster into those cells that have a higher level of metabolism. In some cells, the presence of ion fractions with different metabolic rates (fast and slow fractions) was discovered, which is associated with their different states inside the cell. Ions can be present in a cell in a free ionized form and in a non-ionized state associated with proteins, nucleic acids, and phospholipids. Almost all calcium and magnesium are found in protoplasm in bound form. The mineral anions of the cell are apparently entirely in a free state.

The rate of penetration of cations into the cell can differ by tens or hundreds of times (Table 10).

As for anions, monovalent ones penetrate several times faster than divalent ones. An exceptionally high permeability of anions is observed for erythrocytes. According to the rate of penetration into human erythrocytes, anions can be arranged in the following series: I (1.24) > CNS - (1.09), NO 3 - (l.09) > Cl - (1.00) > SO 4 2- ( 0.21) > HPO 4 2- (0.15).

Rice. 27. Dependence of the flow of potassium ions into erythrocytes on their concentration in the medium. The abscissa axis is the concentration of potassium ions in the medium, mM; along the ordinate - the flow of potassium ions into erythrocytes, µM/g h

The magnitude of ion fluxes into the cell does not depend linearly on their concentration. With an increase in the concentration of the ion in the external environment, the flux initially increases rapidly, and then its increase decreases. This can be seen in curve (1), in Figure 27, which shows the dependence of the flow of potassium ions into human erythrocytes on its concentration in the medium. This curve consists of two components. One of them (2) reflects a linear relationship - this is a passive component and reflects diffusion. The other component (3) indicates the saturation process and is associated with ion transport and energy consumption, therefore it is called active and can be expressed by the Michaelis-Menten formula.

When the cell is excited and damaged, a redistribution of mineral ions occurs between the cell and the environment: the cells lose potassium ions and are enriched with sodium and chlorine ions. Physiological activity is accompanied by an increase in the rate of exchange of cellular ions for the corresponding ions of the environment and an increase in permeability for ions.

With each impulse running along a nerve fiber, the fiber loses a certain amount of potassium ions and approximately the same amount of sodium ions enters the fiber (Table 11). When the cell is excited, the permeability for lithium, rubidium, cesium, choline, and calcium ions also increases. Thus, with one contraction of skeletal muscle, the entry of calcium into the cell increases by 0.2 pmol/cm 2 .

It has now been proven that ionic asymmetry, inherent in all living cells, is ensured by the activity of membranes that have the function of active transport. With its help, sodium ions are pumped out of the cell, and potassium ions are introduced into the cell. This transport function is carried out by enzyme systems with ATPase activity dependent on potassium and sodium.

The transport diagram of potassium and sodium ions is presented in Figure 28. It is believed that when the form of the carrier x changes to y, when ATP energy is required, phosphorylation occurs: x + ATP → xATP → xP + ADP, where xP corresponds to y.

Rice. 28. Scheme of transport of sodium and potassium ions through the surface membrane (according to Glynn)

The membranes of the sarcoplasmic reticulum of muscle fibers have a powerful active transport system that transports potassium ions in a certain direction. It is unknown what the specific mechanism of operation of the transport system is. There are ideas about mobile single carriers, and about collective transport, and about relay transmission.

Positively charged potassium ions into the environment from the cytoplasm of the cell in the process of establishing osmotic equilibrium. Organic acid anions, which neutralize the charge of potassium ions in the cytoplasm, cannot leave the cell, however, potassium ions, the concentration of which in the cytoplasm is high compared to the environment, diffuse from the cytoplasm until the electrical charge they create begins to balance their concentration gradient on the cell membrane.

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✪ Membrane potentials - Part 1

✪ Resting potential: - 70 mV. Depolarization, repolarization

✪ Resting potential

Subtitles

I'll draw a small cell. This will be a typical cell, and it is filled with potassium. We know that cells like to store it inside themselves. Lots of potassium. Let its concentration be somewhere around 150 millimoles per liter. Huge amount of potassium. Let's put this in parentheses because parentheses represent concentration. There is also some potassium present externally. Here the concentration will be approximately 5 millimoles per liter. I'll show you how the concentration gradient will be established. It doesn't happen on its own. This requires a lot of energy. Two potassium ions are pumped into the cell, and at the same time three sodium ions leave the cell. This is how potassium ions get inside initially. Now that they're inside, will they stay there on their own? Of course not. They find anions, small molecules or atoms with a negative charge, and settle near them. Thus the total charge becomes neutral. Each cation has its own anion. And usually these anions are proteins, some kind of structures that have a negative side chain. It could be chloride, or, for example, phosphate. Anything. Any of these anions will do. I'll draw a few more anions. So here are two potassium ions that just got inside the cell, this is what it all looks like now. If everything is good and static, then this is what they look like. And in fact, to be completely fair, there are also small anions that are found here along with potassium ions. The cell has small holes through which potassium can leak out. Let's see what this will look like and how it will affect what's happening here. So we have these little channels. Only potassium can pass through them. That is, these channels are very specific for potassium. Nothing else can pass through them. Neither anions nor proteins. Potassium ions seem to be looking for these channels and reasoning: “Wow, how interesting! There's so much potassium here! We should go outside." And all these potassium ions simply leave the cell. They go outside. And as a result, an interesting thing happens. Most of them have moved outwards. But there are already several potassium ions outside. I said there was this little ion here and it could theoretically get in. He can enter this cell if he wants. But the fact is that in total, in total, you have more movements outward than inward. Now I'm erasing this path because I want you to remember that we have more potassium ions that want to come out because of the concentration gradient. This is the first stage. Let me write this down. The concentration gradient causes potassium to move outward. Potassium begins to move outward. Leaves the cage. What then? Let me draw him in the process of going outside. This potassium ion is now here, and this one is here. Only anions remain. They remained after the potassium left. And these anions begin to produce a negative charge. Very large negative charge. Only a few anions moving back and forth create a negative charge. And the potassium ions on the outside think this is all very interesting. There is a negative charge here. And since it is there, they are attracted to it, since they themselves have a positive charge. They are drawn to a negative charge. They want to come back. Now think about it. You have a concentration gradient that pushes potassium out. But, on the other hand, there is a membrane potential - in this case negative - which arises due to the fact that the potassium has left behind an anion. This potential stimulates potassium to flow back. One force, concentration, pushes the potassium ion out, another force, membrane potential, which is created by potassium, forces it back in. I'll free up some space. Now I'll show you something interesting. Let's construct two curves. I'll try not to miss anything on this slide. I'll draw everything here and then a small fragment of it will be visible. We construct two curves. One of them will be for the concentration gradient, and the other will be for the membrane potential. These will be the potassium ions on the outside. If you follow them over time - this time - you get something like this. Potassium ions tend to come out and reach equilibrium at a certain point. Let's do the same with time on this axis. This will be our membrane potential. We start at the zero time point and get a negative result. The negative charge will become larger and larger. We start at the zero point of the membrane potential, and it is at the point where potassium ions begin to flow out that the following happens. In general terms, everything is very similar, but it occurs as if in parallel with changes in the concentration gradient. And when these two values ​​equalize each other, when the number of potassium ions going out is equal to the number of potassium ions coming back in, you get this plateau. And it turns out that the charge is minus 92 millivolts. At this point, where there is practically no difference in terms of the total movement of potassium ions, equilibrium is observed. It even has its own name - “equilibrium potential for potassium”. When the value reaches minus 92 - and it differs depending on the type of ions - when minus 92 is reached for potassium, a potential equilibrium is created. Let me write that the charge for potassium is minus 92. This only happens when the cell is permeable to only one element, for example, potassium ions. And still a question may arise. You may be thinking, “Okay, wait a second! If the potassium ions move outward—which they do—then don't we have a lower concentration at a certain point because the potassium has already left here, and the higher concentration here is achieved by the potassium moving outward?” Technically it is. Here, outside, there are more potassium ions. And I didn't mention that the volume also changes. Here a higher concentration is obtained. And the same is true for the cell. Technically there is a lower concentration. But I didn't actually change the value. And the reason is this. Look at these values, these are moths. And this is a huge number, don’t you agree? 6.02 times 10 to the power of minus 23 is not a small number at all. And if you multiply it by 5, you get approximately - let me quickly calculate what we got. 6 times 5 is 30. And here are millimoles. From 10 to 20 moles. This is just a huge amount of potassium ions. And to create a negative charge, you need very little of them. That is, the changes caused by the movements of ions will be insignificant compared to 10 to the 20th power. This is why changes in concentration are not taken into account.

History of discovery

The resting potential for most neurons is on the order of −60 mV - −70 mV. Cells of non-excitable tissues also have a potential difference on the membrane, which is different for cells of different tissues and organisms.

Formation of the resting potential

The PP is formed in two stages.

First stage: the creation of slight (-10 mV) negativity inside the cell due to the unequal asymmetric exchange of Na + for K + in a ratio of 3: 2. As a result, more positive charges leave the cell with sodium than return to it with potassium. This feature of the sodium-potassium pump, which exchanges these ions through the membrane with the expenditure of ATP energy, ensures its electrogenicity.

The results of the activity of membrane ion exchanger pumps at the first stage of PP formation are as follows:

1. Deficiency of sodium ions (Na +) in the cell.

2. Excess potassium ions (K +) in the cell.

3. The appearance of a weak electric potential (-10 mV) on the membrane.

Second phase: creation of significant (-60 mV) negativity inside the cell due to the leakage of K + ions from it through the membrane. Potassium ions K+ leave the cell and take away positive charges from it, bringing the negative charge to −70 mV.

So, the resting membrane potential is a deficiency of positive electrical charges inside the cell, resulting from the leakage of positive potassium ions from it and the electrogenic action of the sodium-potassium pump.

I expressed the idea of ​​two forms of convertible energy in 1975. Two years later, this point of view was supported by Mitchell. Meanwhile, in A. Glagolev’s group, experiments began to test one of the predictions of this new concept.

I reasoned as follows. If the proton potential is a bargaining chip, then the cell must have a sufficient number of such “currency notes”.

This requirement was met when it came to ATP. The cell always contains fairly large amounts of ATP, and measures have been taken to stabilize this amount under changing conditions - continuously varying rates of ATP formation and use. There is a special substance - creatine phosphate, which is involved in only one reaction - ADP phosphorylation:

ADP + creatine phosphate ⇔ ATP + creatine.

When ATP is in excess and ADP is in short supply, the reaction goes from right to left and creatine phosphate accumulates, which under these conditions becomes much more abundant than ATP. But as soon as the level of ADP increases and ATP decreases, the reaction changes direction, and creatine phosphate turns out to be a supplier of ATP. Thus, creatine phosphate performs its function as a stabilizer, a buffer of ATP levels.

What about the proton potential?

A simple calculation allows you to convert one energy “currency” to another. This calculation shows that the amount of energy accumulated, for example, by a bacterial cell in the form of a proton potential, turns out to be almost a thousand times less than the amount of ATP if the proton potential is in electrical form. This quantity is of the same order as the number of potential generators and consumers in the bacterial membrane.

This situation creates a special need for a buffer system that stabilizes the level of the proton potential. Otherwise, even a short-term excess of the total speed of potential-consuming processes over the speed of its generation will lead to the disappearance of the potential and the stop of all systems powered by the potential.

So, there must be a buffer for the proton potential, like creatine phosphate for ATP. But what kind of component did nature select for such a role?

While thinking about this problem, I tried to find some potential-related biological system whose function was unknown.

One of the old mysteries of biology: why does a cell absorb potassium ions and expel sodium ions, creating a costly asymmetry in the distribution of these ions with similar properties between the cytoplasm and the environment? In almost any living cell, there are much more potassium ions than sodium ions, while in the environment sodium is in a huge excess over potassium. Maybe Na+ is poison for the cell?

No, that's not true. Although some enzyme systems do indeed work better in KCl than in NaCl, this seems to be a secondary adaptation to the “high-potassium” and “low-sodium” internal environment of the cell. Over a huge period of biological evolution, the cell could adapt to the natural ratio of alkali metal ions in the external environment. Halophilic bacteria live in a saturated solution of NaCl, and the concentration of Na + in their cytoplasm sometimes reaches a mole per liter, which is almost a thousand times higher than the concentration of Na + in ordinary cells. So Na+ is not poison.

Note that the same halophilic bacteria maintain an intracellular concentration of K + of about 4 moles per liter, spending colossal amounts of energy resources on the scale of the cell to create a sodium-potassium gradient.

It is known that excitable animal cells, such as neurons, use a sodium-potassium gradient to conduct nerve impulses. But what about other types of cells, such as bacteria?

Let's look at the mechanism of K+ and Na+ transport across the bacterial membrane. It is known that between the cytoplasm of the bacterium and the external environment there is a difference in electrical potentials, maintained by the work of generator proteins in the bacterial membrane. By pumping protons from inside the cell to the outside, generator proteins thereby charge the inside of the bacterium negatively. Under these conditions, the accumulation of K + ions inside the cell could occur simply due to electrophoresis - the movement of a positively charged potassium ion into the negatively charged cytoplasm of the bacterium.

In this case, the potassium flow should discharge the membrane, previously charged by proton generators.

In turn, discharge of the membrane should immediately activate the generators.

This means that the energy resources spent on generating the electrical potential difference between the cell and the environment will be used to concentrate K + ions inside the cell. The final balance of such a process will be the exchange of intracellular H + ions for extracellular K + ions (H + ions are pumped out by generator proteins, K + ions enter inside, moving in the electric field created by the movement of H + ions).

Therefore, not only an excess of K + ions will be created inside the cell, but also a deficiency of H + ions.

This deficiency can be used to pump out Na+ ions. You can do this as follows. It is known that bacteria have a special carrier of sodium ions that exchanges Na + for H + (this carrier is called the Na + /H + antiporter). Under conditions of H+ deficiency in the cytoplasm, the antiport can compensate for proton deficiency by transferring H+ from the external environment into the cell. The transporter can produce such an antiport in only one way: by exchanging external for internal Na +. This means that the movement of H + ions into the cell can be used to pump out Na + ions from the same cell.

So we created a potassium-sodium gradient: K + accumulated inside the cell and Na + was pumped out from there. The driving force behind these processes was the proton potential created by the generator proteins. (The direction of the potential was such that the inside of the cell became negatively charged and there was a shortage of hydrogen ions.)

Let us now assume that the proton generators are turned off for some reason. What will happen to the potassium-sodium gradient under these new conditions?

Of course, it will dissipate: K + ions will flow out of the cell into the environment, where there are few of them, Na + ions will enter inside, where these ions are in short supply.

But here's what's interesting. As the potassium-sodium gradient dissipates, it will itself turn out to be a generator of proton potential in the same direction that was formed during the operation of generator proteins.

Indeed, the release of the K + ion as a positively charged particle creates a diffusion potential difference on the cell membrane with a minus sign inside the cell. The entry of Na + with the participation of Na + /H + - antiporter will be accompanied by the release of H +, that is, the creation of a deficiency of H + inside the cell.

So what happens? When generator proteins operate, the proton potential they create is used to form a potassium-sodium gradient. But when they are turned off (or their power is not enough to satisfy the numerous potential consumers), the potassium-sodium gradient, dissipating, begins to generate a proton potential.

So this is the proton potential buffer, the same buffer that is so necessary for the operation of membrane energy systems!

This concept can be schematically represented as follows:

Potassium-sodium gradient ↓ external energy resources → proton potential → work.

But if this scheme is correct, then the potassium-sodium gradient should prolong the cell’s performance in conditions when energy resources are depleted.

A. Glagolev and I. Brown checked the validity of this conclusion. A mutant of Escherichia coli was taken that lacked proton ATP synthetase. For such a mutant, the oxidation of substrates with oxygen is the only energy resource available to generate the proton potential. As was shown at one time by J. Adler and his colleagues, the mutant is mobile as long as there is oxygen in the medium.

Glagolev and Brown repeated Adler's experiment and became convinced that the depletion of oxygen in the solution actually stops bacteria if they are in an environment with KCl. Under these conditions, there is no potassium-sodium gradient: there is a lot of potassium in the cells and in the environment, but there is no sodium either here or here.

Now let's take a medium with NaCl. Under such conditions, there should be both gradients of interest to us: potassium (a lot of potassium inside and little outside) and sodium (a lot of sodium outside and little inside). The hypothesis predicted that in such a situation mobility would remain for some time even in oxygen-free conditions, since energy conversion was possible:

potassium-sodium gradient → proton potential → flagella rotation.

Indeed, the bacteria moved for another 15-20 minutes after the measuring device registered a zero level of Cb in the medium.

But the experience with salt-loving bacteria, which transport very large quantities of K + and Na + ions to create a potassium-sodium gradient, turned out to be especially clear, as one would expect. Such bacteria quickly stopped in the dark under oxygen-free conditions if there was KCl in the medium, and were still moving nine (!) hours later if KCl was replaced with NaCl.

This value - nine hours - is interesting primarily as an illustration of the volume of the energy reservoir that represents the potassium-sodium gradient in salt-loving bacteria. In addition, it takes on a special meaning if we remember that salt-loving bacteria have bacteriorhodopsin and, therefore, are capable of converting light energy into proton potential. It is clear that such a transformation is possible only during daylight hours. What about at night? So it turns out that the energy stored during the day in the form of a potassium-sodium gradient is enough for the whole night.

The assertion that the potassium-sodium gradient plays the role of a proton potential buffer allows us to understand not only the biological function of this gradient, but also the reason that for many years prevented the elucidation of its significance for the life of the cell. The idea of ​​a buffering role for the potassium-sodium gradient could not have been conceived until the proton potential was discovered and proven to serve as a convertible form of energy. All these years, the problem of potassium and sodium was simply waiting in the wings.

Article for the “bio/mol/text” competition: The resting potential is an important phenomenon in the life of all cells in the body, and it is important to know how it is formed. However, this is a complex dynamic process, difficult to comprehend in its entirety, especially for junior students (biological, medical and psychological specialties) and unprepared readers. However, when considered point by point, it is quite possible to understand its main details and stages. The work introduces the concept of the resting potential and highlights the main stages of its formation using figurative metaphors that help to understand and remember the molecular mechanisms of the formation of the resting potential.

Membrane transport structures - sodium-potassium pumps - create the prerequisites for the emergence of a resting potential. These prerequisites are the difference in ion concentration on the inner and outer sides of the cell membrane. The difference in sodium concentration and the difference in potassium concentration manifest itself separately. An attempt by potassium ions (K+) to equalize their concentration on both sides of the membrane leads to its leakage from the cell and the loss of positive electrical charges along with them, due to which the overall negative charge of the inner surface of the cell is significantly increased. This "potassium" negativity constitutes the majority of the resting potential (−60 mV on average), and a smaller portion (−10 mV) is the "exchange" negativity caused by the electrogenicity of the ion exchange pump itself.

Let's take a closer look.

Why do we need to know what resting potential is and how it arises?

Do you know what “animal electricity” is? Where do “biocurrents” come from in the body? How can a living cell located in an aquatic environment turn into an “electric battery” and why does it not immediately discharge?

These questions can only be answered if we know how the cell creates its electrical potential difference (resting potential) across the membrane.

It is quite obvious that in order to understand how the nervous system works, it is necessary to first understand how its individual nerve cell, the neuron, works. The main thing that underlies the work of a neuron is the movement of electrical charges through its membrane and, as a result, the appearance of electrical potentials on the membrane. We can say that a neuron, preparing for its nervous work, first stores energy in electrical form, and then uses it in the process of conducting and transmitting nervous excitation.

Thus, our very first step to studying the functioning of the nervous system is to understand how the electrical potential appears on the membrane of nerve cells. This is what we will do, and we will call this process formation of the resting potential.

Definition of the concept of “resting potential”

Normally, when a nerve cell is at physiological rest and ready to work, it has already experienced a redistribution of electrical charges between the inner and outer sides of the membrane. Due to this, an electric field arose, and an electric potential appeared on the membrane - resting membrane potential.

Thus, the membrane becomes polarized. This means that it has different electrical potentials on the outer and inner surfaces. The difference between these potentials is quite possible to register.

This can be verified if a microelectrode connected to a recording unit is inserted into the cell. As soon as the electrode gets inside the cell, it instantly acquires some constant electronegative potential with respect to the electrode located in the fluid surrounding the cell. The value of the intracellular electrical potential in nerve cells and fibers, for example, the giant nerve fibers of the squid, at rest is about −70 mV. This value is called the resting membrane potential (RMP). At all points of the axoplasm this potential is almost the same.

Nozdrachev A.D. and others. Beginnings of physiology.

A little more physics. Macroscopic physical bodies, as a rule, are electrically neutral, i.e. they contain both positive and negative charges in equal quantities. You can charge a body by creating an excess of charged particles of one type in it, for example, by friction against another body, in which an excess of charges of the opposite type is formed. Considering the presence of an elementary charge ( e), the total electric charge of any body can be represented as q= ±N× e, where N is an integer.

Resting potential- this is the difference in electrical potentials present on the inner and outer sides of the membrane when the cell is in a state of physiological rest. Its value is measured from inside the cell, it is negative and averages −70 mV (millivolts), although it can vary in different cells: from −35 mV to −90 mV.

It is important to consider that in the nervous system, electrical charges are not represented by electrons, as in ordinary metal wires, but by ions - chemical particles that have an electrical charge. In general, in aqueous solutions, it is not electrons that move in the form of electric current, but ions. Therefore, all electrical currents in cells and their environment are ion currents.

So, the inside of the cell at rest is negatively charged, and the outside is positively charged. This is characteristic of all living cells, with the possible exception of red blood cells, which, on the contrary, are negatively charged on the outside. More specifically, it turns out that positive ions (Na + and K + cations) will predominate outside the cell around the cell, and negative ions (anions of organic acids that are not able to move freely through the membrane, like Na + and K +) will prevail inside.

Now we just have to explain how everything turned out this way. Although, of course, it is unpleasant to realize that all our cells except red blood cells only look positive on the outside, but on the inside they are negative.

The term “negativity,” which we will use to characterize the electrical potential inside the cell, will be useful to us to easily explain changes in the level of the resting potential. What is valuable about this term is that the following is intuitively clear: the greater the negativity inside the cell, the lower the potential is shifted to the negative side from zero, and the less negativity, the closer the negative potential is to zero. This is much easier to understand than to understand every time what exactly the expression “potential increases” means - an increase in absolute value (or “modulo”) will mean a shift of the resting potential down from zero, and simply an “increase” means a shift of the potential up to zero. The term "negativity" does not create such problems of ambiguity of understanding.

The essence of the formation of the resting potential

Let's try to figure out where the electric charge of nerve cells comes from, although no one rubs them, as physicists do in their experiments with electric charges.

Here one of the logical traps awaits the researcher and student: the internal negativity of the cell does not arise due to the appearance of extra negative particles(anions), but, on the contrary, due to loss of a certain amount of positive particles(cations)!

So where do positively charged particles go from the cell? Let me remind you that these are sodium ions - Na + - and potassium - K + that have left the cell and accumulated outside.

The main secret of the appearance of negativity inside the cell

Let’s immediately reveal this secret and say that the cell loses some of its positive particles and becomes negatively charged due to two processes:

1. first, she exchanges “her” sodium for “foreign” potassium (yes, some positive ions for others, equally positive);
2. then these “replaced” positive potassium ions leak out of it, along with which positive charges leak out of the cell.

We need to explain these two processes.

The first stage of creating internal negativity: exchange of Na + for K +

Proteins are constantly working in the membrane of a nerve cell. exchanger pumps(adenosine triphosphatases, or Na + /K + -ATPases) embedded in the membrane. They exchange the cell’s “own” sodium for external “foreign” potassium.

But when one positive charge (Na +) is exchanged for another of the same positive charge (K +), no deficiency of positive charges can arise in the cell! Right. But, nevertheless, due to this exchange, very few sodium ions remain in the cell, because almost all of them have gone outside. And at the same time, the cell is overflowing with potassium ions, which were pumped into it by molecular pumps. If we could taste the cytoplasm of the cell, we would notice that as a result of the work of the exchange pumps, it turned from salty to bitter-salty-sour, because the salty taste of sodium chloride was replaced by the complex taste of a rather concentrated solution of potassium chloride. In the cell, the potassium concentration reaches 0.4 mol/l. Solutions of potassium chloride in the range of 0.009-0.02 mol/l have a sweet taste, 0.03-0.04 - bitter, 0.05-0.1 - bitter-salty, and starting from 0.2 and above - a complex taste consisting of salty, bitter and sour.

The important thing here is that exchange of sodium for potassium - unequal. For every cell given three sodium ions she gets everything two potassium ions. This results in the loss of one positive charge with each ion exchange event. So already at this stage, due to unequal exchange, the cell loses more “pluses” than it receives in return. In electrical terms, this amounts to approximately −10 mV of negativity within the cell. (But remember that we still need to find an explanation for the remaining −60 mV!)

To make it easier to remember the operation of exchanger pumps, we can figuratively put it this way: “The cell loves potassium!” Therefore, the cell drags potassium towards itself, despite the fact that it is already full of it. And therefore, it exchanges it unprofitably for sodium, giving 3 sodium ions for 2 potassium ions. And therefore it spends ATP energy on this exchange. And how he spends it! Up to 70% of a neuron’s total energy expenditure can be spent on the operation of sodium-potassium pumps. (That's what love does, even if it's not real!)

By the way, it is interesting that the cell is not born with a ready-made resting potential. She still needs to create it. For example, during differentiation and fusion of myoblasts, their membrane potential changes from −10 to −70 mV, i.e. their membrane becomes more negative - polarized during the process of differentiation. And in experiments on multipotent mesenchymal stromal cells of human bone marrow, artificial depolarization, counteracting the resting potential and reducing cell negativity, even inhibited (depressed) cell differentiation.

Figuratively speaking, we can put it this way: By creating a resting potential, the cell is “charged with love.” This is love for two things:

1. the cell's love for potassium (therefore the cell forcibly drags it towards itself);
2. potassium's love for freedom (therefore potassium leaves the cell that has captured it).

We have already explained the mechanism of saturating the cell with potassium (this is the work of exchange pumps), and the mechanism of potassium leaving the cell will be explained below, when we move on to describing the second stage of creating intracellular negativity. So, the result of the activity of membrane ion exchanger pumps at the first stage of the formation of the resting potential is as follows:

1. Sodium (Na+) deficiency in the cell.
2. Excess potassium (K+) in the cell.
3. The appearance of a weak electric potential (−10 mV) on the membrane.

We can say this: at the first stage, membrane ion pumps create a difference in ion concentrations, or a concentration gradient (difference), between the intracellular and extracellular environment.

Second stage of creating negativity: leakage of K+ ions from the cell

So, what begins in the cell after its membrane sodium-potassium exchanger pumps work with ions?

Due to the resulting sodium deficiency inside the cell, this ion strives to rush inside: dissolved substances always strive to equalize their concentration throughout the entire volume of the solution. But sodium does this poorly, since sodium ion channels are usually closed and open only under certain conditions: under the influence of special substances (transmitters) or when the negativity in the cell decreases (membrane depolarization).

At the same time, there is an excess of potassium ions in the cell compared to the external environment - because the membrane pumps forcibly pumped it into the cell. And he, also trying to equalize his concentration inside and outside, strives, on the contrary, get out of the cage. And he succeeds!

Potassium ions K + leave the cell under the influence of a chemical gradient of their concentration on different sides of the membrane (the membrane is much more permeable to K + than to Na +) and carry away positive charges with them. Because of this, negativity grows inside the cell.

It is also important to understand that sodium and potassium ions do not seem to “notice” each other, they react only “to themselves.” Those. sodium reacts to the same sodium concentration, but “does not pay attention” to how much potassium is around. Conversely, potassium only responds to potassium concentrations and “ignores” sodium. It turns out that to understand the behavior of ions, it is necessary to separately consider the concentrations of sodium and potassium ions. Those. it is necessary to separately compare the concentration of sodium inside and outside the cell and separately - the concentration of potassium inside and outside the cell, but it makes no sense to compare sodium with potassium, as is sometimes done in textbooks.

According to the law of equalization of chemical concentrations, which operates in solutions, sodium “wants” to enter the cell from the outside; it is also drawn there by electrical force (as we remember, the cytoplasm is negatively charged). He wants to, but he can’t, since the membrane in its normal state does not allow him to pass through it well. Sodium ion channels present in the membrane are normally closed. If, nevertheless, a little of it comes in, then the cell immediately exchanges it for external potassium using its sodium-potassium exchanger pumps. It turns out that sodium ions pass through the cell as if in transit and do not stay in it. Therefore, sodium in neurons is always in short supply.

But potassium can easily leave the cell to the outside! The cage is full of him, and she can’t hold him. It exits through special channels in the membrane - "potassium leak channels", which are normally open and release potassium.

K + -leak channels are constantly open at normal values ​​of the resting membrane potential and exhibit bursts of activity at shifts in membrane potential, which last several minutes and are observed at all potential values. An increase in K+ leakage currents leads to hyperpolarization of the membrane, while their suppression leads to depolarization. ...However, the existence of a channel mechanism responsible for leakage currents remained in question for a long time. Only now has it become clear that potassium leakage is a current through special potassium channels.

Zefirov A.L. and Sitdikova G.F. Ion channels of an excitable cell (structure, function, pathology).

From chemical to electrical

And now - once again the most important thing. We must consciously move away from movement chemical particles to the movement electric charges.

Potassium (K+) is positively charged, and therefore, when it leaves the cell, it carries out not only itself, but also a positive charge. Behind it, “minuses” - negative charges - stretch from inside the cell to the membrane. But they cannot leak through the membrane - unlike potassium ions - because... there are no suitable ion channels for them, and the membrane does not allow them to pass through. Remember about the −60 mV of negativity that remains unexplained by us? This is the very part of the resting membrane potential that is created by the leakage of potassium ions from the cell! And this is a large part of the resting potential.

There is even a special name for this component of the resting potential - concentration potential. Concentration potential - this is part of the resting potential created by the deficiency of positive charges inside the cell, formed due to the leakage of positive potassium ions from it.

Well, now a little physics, chemistry and mathematics for lovers of precision.

Electrical forces are related to chemical forces according to the Goldmann equation. Its special case is the simpler Nernst equation, the formula of which can be used to calculate the transmembrane diffusion potential difference based on different concentrations of ions of the same type on different sides of the membrane. So, knowing the concentration of potassium ions outside and inside the cell, we can calculate the potassium equilibrium potential E K:

Where E k - equilibrium potential, R- gas constant, T- absolute temperature, F- Faraday's constant, K + ext and K + int - concentrations of K + ions outside and inside the cell, respectively. The formula shows that to calculate the potential, the concentrations of ions of the same type - K + - are compared with each other.

More precisely, the final value of the total diffusion potential, which is created by the leakage of several types of ions, is calculated using the Goldman-Hodgkin-Katz formula. It takes into account that the resting potential depends on three factors: (1) the polarity of the electric charge of each ion; (2) membrane permeability R for each ion; (3) [concentrations of the corresponding ions] inside (internal) and outside the membrane (external). For the squid axon membrane at rest, the conductance ratio R K: PNa :P Cl = 1: 0.04: 0.45.

Conclusion

So, the resting potential consists of two parts:

1. −10 mV, which are obtained from the “asymmetrical” operation of the membrane pump-exchanger (after all, it pumps more positive charges (Na +) out of the cell than it pumps back with potassium).
2. The second part is potassium leaking out of the cell all the time, carrying away positive charges. His main contribution is: −60 mV. In total, this gives the desired −70 mV.

Interestingly, potassium will stop leaving the cell (more precisely, its input and output are equalized) only at a cell negative level of −90 mV. In this case, the chemical and electrical forces that push potassium through the membrane are equal, but direct it in opposite directions. But this is hampered by sodium constantly leaking into the cell, which carries with it positive charges and reduces the negativity for which potassium “fights.” And as a result, the cell maintains an equilibrium state at a level of −70 mV.

Now the resting membrane potential is finally formed.

Scheme of operation of Na + /K + -ATPase clearly illustrates the “asymmetrical” exchange of Na + for K +: pumping out excess “plus” in each cycle of the enzyme leads to negative charging of the inner surface of the membrane. What this video doesn't say is that the ATPase is responsible for less than 20% of the resting potential (−10 mV): the remaining "negativity" (−60 mV) comes from K ions leaving the cell through "potassium leak channels" +, seeking to equalize their concentration inside and outside the cell.

Literature

1. Jacqueline Fischer-Lougheed, Jian-Hui Liu, Estelle Espinos, David Mordasini, Charles R. Bader, et. al.. (2001). Human Myoblast Fusion Requires Expression of Functional Inward Rectifier Kir2.1 Channels . J Cell Biol. 153 , 677-686;
2. Liu J.H., Bijlenga P., Fischer-Lougheed J. et al. (1998). Role of an inward rectifier K+ current and of hyperpolarization in human myoblast fusion. J. Physiol. 510 , 467–476;
3. Sarah Sundelacruz, Michael Levin, David L. Kaplan. (2008). Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells. PLoS ONE. 3 , e3737;
4. Pavlovskaya M.V. and Mamykin A.I. Electrostatics. Dielectrics and conductors in an electric field. Direct current / Electronic manual for the general course of physics. SPb: St. Petersburg State Electrotechnical University;
5. Nozdrachev A.D., Bazhenov Yu.I., Barannikova I.A., Batuev A.S. and others. The beginnings of physiology: Textbook for universities / Ed. acad. HELL. Nozdracheva. St. Petersburg: Lan, 2001. - 1088 pp.;
6. Makarov A.M. and Luneva L.A. Fundamentals of electromagnetism / Physics at a technical university. T. 3;
7. Zefirov A.L. and Sitdikova G.F. Ion channels of an excitable cell (structure, function, pathology). Kazan: Art Cafe, 2010. - 271 p.;
8. Rodina T.G. Sensory analysis of food products. Textbook for university students. M.: Academy, 2004. - 208 pp.;
9. Kolman, J. and Rehm, K.-G. Visual biochemistry. M.: Mir, 2004. - 469 pp.;
10. Shulgovsky V.V. Fundamentals of neurophysiology: A textbook for university students. M.: Aspect Press, 2000. - 277 pp..

So, there are two facts that need to be considered in order to understand the mechanisms that maintain the resting membrane potential.

1 . The concentration of potassium ions in the cell is much higher than in the extracellular environment. 2 . The membrane at rest is selectively permeable to K +, and for Na + the permeability of the membrane at rest is insignificant. If we take the permeability for potassium to be 1, then the permeability for sodium at rest is only 0.04. Hence, there is a constant flow of K+ ions from the cytoplasm along a concentration gradient. The potassium current from the cytoplasm creates a relative deficiency of positive charges on the inner surface; the cell membrane is impenetrable for anions; as a result, the cell cytoplasm becomes negatively charged in relation to the environment surrounding the cell. This potential difference between the cell and the extracellular space, the polarization of the cell, is called the resting membrane potential (RMP).

The question arises: why does the flow of potassium ions not continue until the concentrations of the ion outside and inside the cell are balanced? It should be remembered that this is a charged particle, therefore, its movement also depends on the charge of the membrane. The intracellular negative charge, which is created due to the flow of potassium ions from the cell, prevents new potassium ions from leaving the cell. The flow of potassium ions stops when the action of the electric field compensates for the movement of the ion along the concentration gradient. Consequently, for a given difference in ion concentrations on the membrane, the so-called EQUILIBRIUM POTENTIAL for potassium is formed. This potential (Ek) is equal to RT/nF *ln /, (n is the valency of the ion.) or

Ek=61.5 log/

The membrane potential (MP) largely depends on the equilibrium potential of potassium; however, some sodium ions still penetrate into the resting cell, as well as chlorine ions. Thus, the negative charge that the cell membrane has depends on the equilibrium potentials of sodium, potassium and chlorine and is described by the Nernst equation. The presence of this resting membrane potential is extremely important because it determines the cell's ability to excite - a specific response to a stimulus.

Cell excitation

IN excitement cells (transition from a resting to an active state) occurs when the permeability of ion channels for sodium and sometimes for calcium increases. The reason for the change in permeability can be a change in the membrane potential - electrically excitable channels are activated, and the interaction of membrane receptors with a biologically active substance - receptor - controlled channels, and mechanical action. In any case, for the development of arousal it is necessary initial depolarization - a slight decrease in the negative charge of the membrane, caused by the action of a stimulus. An irritant can be any change in the parameters of the external or internal environment of the body: light, temperature, chemicals (effects on taste and olfactory receptors), stretching, pressure. Sodium rushes into the cell, an ion current occurs and the membrane potential decreases - depolarization membranes.

Table 4

Change in membrane potential upon cell excitation.

Please note that sodium enters the cell along a concentration gradient and an electrical gradient: the sodium concentration in the cell is 10 times lower than in the extracellular environment and the charge relative to the extracellular is negative. Potassium channels are also activated at the same time, but sodium (fast) channels are activated and inactivated within 1 - 1.5 milliseconds, and potassium channels longer.

Changes in membrane potential are usually depicted graphically. The top figure shows the initial depolarization of the membrane - the change in potential in response to the action of a stimulus. For each excitable cell there is a special level of membrane potential, upon reaching which the properties of sodium channels sharply change. This potential is called critical level of depolarization (KUD). When the membrane potential changes to KUD, fast, voltage-dependent sodium channels open, and a flow of sodium ions rushes into the cell. When positively charged ions enter the cell, the positive charge increases in the cytoplasm. As a result of this, the transmembrane potential difference decreases, the MP value decreases to 0, and then, as sodium continues to enter the cell, the membrane is recharged and the charge is reversed (overshoot) - now the surface becomes electronegative with respect to the cytoplasm - the membrane is completely DEPOLARIZED - middle picture. No further change in charge occurs because sodium channels are inactivated– more sodium cannot enter the cell, although the concentration gradient changes very slightly. If the stimulus has such a force that it depolarizes the membrane to CUD, this stimulus is called threshold; it causes excitation of the cell. The potential reversal point is a sign that the entire range of stimuli of any modality has been translated into the language of the nervous system - excitation impulses. Impulses or excitation potentials are called action potentials. Action potential (AP) is a rapid change in membrane potential in response to a stimulus of threshold strength. AP has standard amplitude and time parameters that do not depend on the strength of the stimulus - the “ALL OR NOTHING” rule. The next stage is the restoration of the resting membrane potential - repolarization(bottom figure) is mainly due to active ion transport. The most important process of active transport is the work of the Na/K pump, which pumps sodium ions out of the cell while simultaneously pumping potassium ions into the cell. The restoration of the membrane potential occurs due to the flow of potassium ions from the cell - potassium channels are activated and allow potassium ions to pass through until the equilibrium potassium potential is reached. This process is important because until the MPP is restored, the cell is not able to perceive a new impulse of excitation.

HYPERPOLARIZATION is a short-term increase in MP after its restoration, which is caused by an increase in membrane permeability for potassium and chlorine ions. Hyperpolarization occurs only after AP and is not typical for all cells. Let us once again try to graphically represent the phases of the action potential and the ionic processes underlying changes in membrane potential (Fig. 9). On the abscissa axis we plot the values ​​of the membrane potential in millivolts, on the ordinate axis we plot time in milliseconds.

1. Depolarization of the membrane to CUD - any sodium channels can open, sometimes calcium, both fast and slow, and voltage-gated and receptor-gated. It depends on the type of stimulus and the type of cells

2. Rapid entry of sodium into the cell - fast, voltage-dependent sodium channels open, and depolarization reaches the potential reversal point - the membrane is recharged, the sign of the charge changes to positive.

3. Restoration of the potassium concentration gradient - pump operation. Potassium channels are activated, potassium moves from the cell to the extracellular environment - repolarization, restoration of MPP begins

4. Trace depolarization, or negative trace potential - the membrane is still depolarized relative to the MPP.

5. Trace hyperpolarization. Potassium channels remain open and the additional potassium current hyperpolarizes the membrane. After this, the cell returns to its original level of MPP. The duration of the AP ranges from 1 to 3-4 ms for different cells.

Figure 9 Action potential phases

Pay attention to the three potential values, important and constant for each cell, its electrical characteristics.

1. MPP - electronegativity of the cell membrane at rest, providing the ability to excite - excitability. In the figure, MPP = -90 mV.

2. CUD - critical level of depolarization (or threshold for generation of membrane action potential) - this is the value of the membrane potential, upon reaching which they open fast, voltage-dependent sodium channels and the membrane is recharged due to the entry of positive sodium ions into the cell. The higher the electronegativity of the membrane, the more difficult it is to depolarize it to CUD, the less excitable such a cell.

3. Potential reversal point (overshoot) - this value positive membrane potential, at which positively charged ions no longer penetrate the cell - short-term equilibrium sodium potential. In the figure + 30 mV. The total change in membrane potential from –90 to +30 will be 120 mV for a given cell, this value is the action potential. If this potential arises in a neuron, it will spread along the nerve fiber; if in muscle cells, it will spread along the muscle fiber membrane and lead to contraction; in glandular cells, to secretion, to cell action. This is the specific response of the cell to the action of the stimulus, excitation.

When exposed to a stimulus subliminal strength incomplete depolarization occurs - LOCAL RESPONSE (LO). Incomplete or partial depolarization is a change in membrane charge that does not reach the critical depolarization level (CLD).

Figure 10. Change in membrane potential in response to a stimulus of subthreshold strength - local response

The local response has basically the same mechanism as AP, its ascending phase is determined by the influx of sodium ions, and its descending phase is determined by the release of potassium ions. However, the amplitude of the LO is proportional to the strength of the subthreshold stimulation, and not standard, like that of the AP.