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Why does the cell exchange sodium for potassium? Conditions for the occurrence of the resting membrane potential Why do more potassium ions leave the cell?

The main physiological function of sodium in the human body is to regulate the volume of extracellular fluid, thereby determining blood volume and blood pressure. This function is directly related to sodium and fluid metabolism. In addition, sodium is involved in the process of bone tissue formation, conduction of nerve impulses, etc.

In medicine, in the event of various kinds of electrolyte imbalances, in order to find out the causes of this condition, tests are carried out to determine the concentration of sodium, as well as monitoring the fluid balance (its intake and excretion).

In the human body, the mass of fluid occupies approximately 60%, that is, a person weighing 70 kg contains approximately 40 liters of fluid, of which about 25 liters are contained in the cells (intracellular fluid - CL) and 14 liters are outside the cells (extracellular fluid - ExtraQoL). Of the total amount of extracellular fluid, approximately 3.5 liters is occupied by blood plasma (blood fluid located inside the vascular system) and about 10.5 liters by interstitial fluid (IF), filling the space in the tissues between cells (see Fig. 1)

Figure 1. Fluid distribution in the body of an adult weighing 70 kg

The total amount of fluid in the body and maintaining a constant level of its distribution between compartments help ensure the full functioning of all organs and systems, which, undoubtedly, is the key to good health. The exchange of water between intracellular fluid and extracellular fluid occurs through cell membranes. The osmolarity of the fluid solutions on both sides of the membrane directly influences this exchange. Under the condition of osmotic equilibrium, the liquid will not move, that is, its volumes in the compartments will not change. In a healthy person, the osmolarity of intracellular fluid and blood plasma (extracellular fluid) is maintained at approximately 80-295 mOsmol/kg.

The role of sodium in the regulation of extracellular fluid volume

Osmolarity is the sum of the concentration of all kinetic particles in 1 liter of solution, that is, it depends on the total concentration of dissolved ions. In the human body, osmolarity is determined by electrolytes, since in liquid media (intra- and extracellular fluid) ions are in relatively high concentrations compared to other dissolved components. Figure 2 demonstrates the distribution of electrolytes between intracellular and extracellular fluids.

Figure 2. Concentration of dissolved components in intracellular and extracellular fluids

It is important to note that for monovalent ions (potassium, sodium) meq/l = mmol/l, and for divalent ions, to calculate the number of mmol/l, meq should be divided by 2.

The left side of the figure (Ex-QF) shows the composition of blood plasma, which is very similar in composition to interstitial fluid (except for the low protein concentration and high chloride concentration)

It can be concluded that the concentration of sodium in the blood plasma is a determining indicator of the volume of extracellular fluid and, as a consequence, the volume of blood.

The extracellular fluid is high in sodium and low in potassium. On the contrary, the cells contain little sodium - the main intracellular cation is potassium. This difference in the concentrations of electrolytes in the extracellular and intracellular fluids is maintained by the mechanism of active ion transport with the participation of the sodium-potassium pump (pump) (see Fig. 3).

Figure 3. Maintaining sodium and potassium concentrations in the QoL and extraQoL

The sodium-potassium pump, localized on cell membranes, is an energy-independent system found in all types of cells. Thanks to this system, sodium ions are removed from cells in exchange for potassium ions. Without such a transport system, potassium and sodium ions would remain in a state of passive diffusion through the cell membrane, which would result in ionic equilibrium between the extracellular and intracellular fluids.

High osmolarity of the extracellular fluid is ensured due to the active transport of sodium ions from the cell, which ensures their high content in the extracellular fluid. Given the fact that osmolarity influences the distribution of fluid between the ECF and the CL, therefore, the volume of extracellular fluid is directly dependent on the sodium concentration.

REGULATION OF WATER BALANCE

The intake of fluid into the human body must be adequate to its removal, otherwise overhydration or dehydration may occur. In order for the excretion (removal) of toxic substances (toxic substances formed in the body during metabolism) to occur, the kidneys must excrete at least 500 ml of urine daily. To this amount you need to add 400 ml of liquid, which is excreted daily through the lungs during breathing, 500 ml - excreted through the skin, and 100 ml - with fecal matter. As a result, the human body loses an average of 1500 ml (1.5 l) of fluid daily.

Note that daily in the human body in the process of metabolism (as a result of a by-product of metabolism) approximately 400 ml of water is synthesized. Thus, in order to maintain a minimum level of water balance, the body must receive at least 1100 ml of water per day. In fact, the daily volume of incoming fluid often exceeds the specified minimum level, while the kidneys, in the process of regulating water balance, do an excellent job of removing excess fluid.

For most people, the average daily urine volume is approximately 1200-1500 ml. If necessary, the kidneys can produce significantly more urine.

Blood plasma osmolarity is associated with the flow of fluid into the body and the process of formation and excretion of urine. For example, if fluid loss is not adequately replaced, extracellular fluid volume decreases and osmolarity increases, resulting in an increase in fluid flow from body cells into the extracellular fluid, thereby restoring its osmolarity and volume to the required level. However, such internal distribution of fluid is effective only for a limited period of time, since this process leads to dehydration (dehydration) of cells, as a result of which the body needs more fluid from outside.

Figure 4 schematically represents the physiological response to fluid deficiency in the body.

Figure 4. Maintaining normal water balance in the body is regulated by the hypothalamic-pituitary system, the feeling of thirst, adequate synthesis of antidiuretic hormone and the full functioning of the kidneys

When there is a deficiency of fluid in the body, high-osmolar blood plasma flows through the hypothalamus, in which osmoreceptors (special cells) analyze the state of the plasma and give a signal to trigger the mechanism of reducing osmolarity by stimulating the secretion of antidiuretic hormone (ADH) in the pituitary gland and the emergence of a feeling of thirst. When thirsty, a person tries to compensate for the lack of fluid from outside by consuming drinks or water. Antidiuretic hormone affects kidney function, thereby preventing the removal of fluid from the body. ADH promotes increased reabsorption (reabsorption) of fluid from the collecting ducts and distal tubules of the kidneys, resulting in the production of relatively small amounts of higher concentration urine. Despite these changes in the blood plasma, modern diagnostic analyzers can assess the degree of hemolysis and measure the actual level of potassium in the plasma of hemolyzed blood samples.

When a large amount of fluid enters the body, the osmolarity of the extracellular fluid decreases. In this case, stimulation of osmoreceptors in the hypothalamus does not occur - the person does not experience a feeling of thirst and the level of antidiuretic hormone does not increase. In order to prevent excessive water load, a large amount of dilute urine is formed in the kidneys.

Note that approximately 8000 ml (8 liters) of fluid enters the gastrointestinal tract daily in the form of gastric, intestinal and pancreatic juices, bile, and saliva. Under normal conditions, approximately 99% of this fluid is reabsorbed and only 100 ml is excreted in the feces. However, disruption of the water conservation function contained in these secretions can lead to water imbalance, which will cause serious disorders of the entire body.

Let us once again pay attention to the factors influencing the normal regulation of water balance in the human body:

  • Feeling thirsty(for thirst to manifest, a person must be conscious)
  • Full functioning of the pituitary gland and hypothalamus
  • Full kidney function
  • Full functioning of the gastrointestinal tract

REGULATION OF SODIUM BALANCE

For the normal functioning and health of the body, maintaining sodium balance is as important as maintaining water balance. In a normal state, the adult human body contains approximately 3000 mmol of sodium. Most of the sodium is contained in the extracellular fluid: blood plasma and interstitial fluid (sodium concentration in them is about 140 mmol/l).

Daily sodium loss is at least 10 mmol/l. To maintain normal balance in the body, these losses must be compensated (replenished). Through diet, people receive significantly more sodium than the body needs to compensate (with food, usually in the form of salty seasonings, a person receives an average of 100-200 mmol of sodium daily). However, despite the wide variability in sodium intake, renal regulation ensures that excess sodium is excreted in the urine, thereby maintaining physiological balance.

The process of excretion (removal) of sodium through the kidneys depends directly on GFR (glomerular filtration rate). A high glomerular filtration rate increases the amount of sodium excreted in the body, and a low GFR rate delays it. Approximately 95-99% of the sodium filtered by the glomerulus is actively reabsorbed as urine passes through the proximal convoluted tubule. By the time the ultrafiltrate enters the distal convoluted tubule, the amount of sodium already filtered in the glomeruli is 1-5%. Whether the remaining sodium is excreted in the urine or reabsorbed into the blood depends directly on the concentration of the adrenal hormone aldosterone in the blood.

Aldosterone enhances the reabsorption of sodium in exchange for hydrogen or potassium ions, thereby affecting the cells of the distal tubules of the kidneys. That is, under the condition of high levels of aldosterone in the blood, most of the remaining sodium is reabsorbed; at low concentrations, sodium is excreted in the urine in large quantities.

Figure 5.

Controls the process of aldosterone production (see Figure 5). Renin- an enzyme that is produced by the kidneys in the cells of the juxtaglomerular apparatus in response to a decrease in blood flow through the renal glomeruli. Since the rate of renal blood flow, like blood flow through other organs, depends on blood volume, and therefore on the concentration of sodium in the blood, renin secretion in the kidneys increases when plasma sodium levels decrease.

Thanks to renin, the enzymatic breakdown of protein, also known as renin substrate. One of the products of this splitting is angiotensinI- a peptide containing 10 amino acids.

Another enzyme is ACE ( angiotensin converting enzyme), which is synthesized mainly in the lungs. During metabolism, ACE separates two amino acids from angiotensin I, which leads to the formation of octopeptide - the hormone angiotensin II .

AngiotensinII has very important properties for the body:

  • Vasoconstriction- constriction of blood vessels, which increases blood pressure and restores normal renal blood flow
  • Stimulates aldosterone production in the cells of the adrenal cortex, thereby activating sodium reabsorption, which helps restore normal blood flow through the kidneys and the total blood volume in the body.

When blood volume and blood pressure increase, heart cells secrete a hormone that is an aldosterone antagonist - ANP ( atrial natriuretic peptide, or PNP). ANP helps reduce sodium reabsorption in the distal tubules of the kidneys, thereby increasing its excretion in the urine. That is, the “feedback” system ensures clear regulation of sodium balance in the body.

Experts say that approximately 1,500 mmol of sodium enters the human body through the gastrointestinal tract every day. Approximately 10 mmol of sodium that is excreted in the feces is reabsorbed. In case of dysfunction of the gastrointestinal tract, the amount of sodium reabsorbed decreases, which leads to its deficiency in the body. When the renal compensation mechanism is impaired, signs of this deficiency begin to appear.

Maintaining a normal sodium balance in the body depends on 3 main factors:

  • Kidney functions
  • Aldosterone secretion
  • Functioning of the gastrointestinal tract

POTASSIUM

Potassium is involved in the conduction of nerve impulses, the process of muscle contraction, and ensures the action of many enzymes. The human body contains on average 3000 mmol of potassium, most of which is found in cells. The potassium concentration in blood plasma is approximately 0.4%. Although its concentration in the blood can be measured, the test result will not objectively reflect the total potassium content in the body. However, to maintain the overall balance of potassium, it is necessary to maintain the desired level of concentration of this element in the blood plasma.

Regulation of potassium balance

The body loses at least 40 mmol of potassium daily in feces, urine and sweat. Maintaining the necessary potassium balance requires replenishing these losses. A diet that contains vegetables, fruit, meat and bread provides approximately 100 mmol of potassium per day. To ensure the necessary balance, excess potassium is excreted in the urine. The process of filtration of potassium, like sodium, occurs in the renal glomeruli (as a rule, it is reabsorbed in the proximal (initial) part of the renal tubules. Fine regulation occurs in the collecting glomeruli and distal tubules (potassium can be reabsorbed or secreted in exchange for sodium ions).

The renin-angiotensin-aldosterone system regulates sodium-potassium metabolism, or rather stimulates it (aldosterone triggers sodium reabsorption and the process of potassium excretion in the urine).

In addition, the amount of potassium excreted in the urine is determined by the function of the kidneys in regulating the acid-base balance (pH) of the blood within physiological normal limits. For example, one mechanism to prevent blood oxidation is to remove excess hydrogen ions from the body in the urine (this occurs by exchanging hydrogen ions for sodium ions in the distal renal tubules). Thus, in acidosis, less sodium can be exchanged for potassium, resulting in the kidneys excreting less potassium. There are other ways of interaction between acid-base status and potassium.

Under normal conditions, approximately 60 mmol of potassium is released into the gastrointestinal tract, where most of it is reabsorbed (the body loses about 10 mmol of potassium in feces). In case of dysfunction of the gastrointestinal tract, the reabsorption mechanism is disrupted, which can lead to potassium deficiency.

Transport of potassium across cell membranes

Low potassium concentrations in the extracellular fluid and high potassium concentrations in the intracellular fluid are regulated by the sodium-potassium pump. Inhibition (inhibition) or stimulation (intensification) of this mechanism affects the concentration of potassium in the blood plasma, as the ratio of concentrations in extracellular and intracellular fluids changes. Note that hydrogen ions compete with potassium ions when passing through cell membranes, that is, the level of potassium in the blood plasma affects the acid-base balance.

A significant decrease or increase in the concentration of potassium in the blood plasma does not at all indicate a deficiency or excess of this element in the body as a whole - it may indicate a violation of the necessary balance of extra- and intracellular potassium.

Regulation of potassium concentration in blood plasma occurs due to the following factors:

  • Potassium intake from food
  • Kidney functions
  • Functions of the gastrointestinal tract
  • Aldosterone production
  • Acid-base balance
  • Sodium-potassium pump

Positively charged potassium ions enter the environment from the cytoplasm of the cell in the process of establishing osmotic equilibrium. Anions of organic acids, 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 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 are trying to get 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 due to 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 stage: 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.

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 themselves 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 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, but ions that move in the form of electric current. 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 look positive only 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 in potential up to zero. The term "negativity" does not create similar 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 identical 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, because 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 a 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 pp.;
  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..

Between the outer surface of the cell and its cytoplasm at rest there is a potential difference of about 0.06-0.09 V, and the cell surface is charged electropositively with respect to the cytoplasm. This potential difference is called resting potential or membrane potential. Accurate measurement of the resting potential is only possible with the help of microelectrodes designed for intracellular current drainage, very powerful amplifiers and sensitive recording instruments - oscilloscopes.

The microelectrode (Fig. 67, 69) is a thin glass capillary, the tip of which has a diameter of about 1 micron. This capillary is filled with saline solution, a metal electrode is immersed in it and connected to an amplifier and an oscilloscope (Fig. 68). As soon as the microelectrode pierces the membrane covering the cell, the oscilloscope beam is deflected down from its original position and established at a new level. This indicates the presence of a potential difference between the outer and inner surfaces of the cell membrane.

The origin of the resting potential is most fully explained by the so-called membrane-ion theory. According to this theory, all cells are covered with a membrane that is unequally permeable to different ions. In this regard, inside the cell in the cytoplasm there are 30-50 times more potassium ions, 8-10 times less sodium ions and 50 times less chlorine ions than on the surface. At rest, the cell membrane is more permeable to potassium ions than to sodium ions. The diffusion of positively charged potassium ions from the cytoplasm to the cell surface gives the outer surface of the membrane a positive charge.

Thus, the surface of the cell at rest carries a positive charge, while the inner side of the membrane turns out to be negatively charged due to chlorine ions, amino acids and other large organic anions that practically do not penetrate the membrane (Fig. 70).

Action potential

If a section of a nerve or muscle fiber is exposed to a sufficiently strong stimulus, then excitation occurs in this section, manifested in a rapid oscillation of the membrane potential and called action potential.

The action potential can be recorded either using electrodes applied to the outer surface of the fiber (extracellular lead) or a microelectrode inserted into the cytoplasm (intracellular lead).

With extracellular abduction, one can find that the surface of the excited area for a very short period, measured in thousandths of a second, becomes charged electronegatively with respect to the resting area.

The cause of the action potential is a change in the ionic permeability of the membrane. When irritated, the permeability of the cell membrane to sodium ions increases. Sodium ions tend to enter the cell because, firstly, they are positively charged and are drawn inward by electrostatic forces, and secondly, their concentration inside the cell is low. At rest, the cell membrane was poorly permeable to sodium ions. Irritation has changed the permeability of the membrane, and the flow of positively charged sodium ions from the external environment of the cell into the cytoplasm significantly exceeds the flow of potassium ions from the cell to the outside. As a result, the inner surface of the membrane becomes positively charged, and the outer surface becomes negatively charged due to the loss of positively charged sodium ions. At this moment the peak of the action potential is recorded.

The increase in membrane permeability to sodium ions lasts for a very short time. Following this, reduction processes occur in the cell, leading to the fact that the permeability of the membrane for sodium ions again decreases, and for potassium ions increases. Since potassium ions are also positively charged, when they leave the cell, they restore the original relationship between the outside and inside the cell.

Accumulation of sodium ions inside the cell during repeated excitation does not occur because sodium ions are constantly evacuated from it due to the action of a special biochemical mechanism called the “sodium pump”. There is also evidence of active transport of potassium ions using the “sodium-potassium pump”.

Thus, according to the membrane-ion theory, the selective permeability of the cell membrane is of decisive importance in the origin of bioelectric phenomena, which determines the different ionic composition on the surface and inside the cell, and, consequently, the different charge of these surfaces. It should be noted that many provisions of the membrane-ion theory are still debatable and require further development.

Both of these elements are in the first group of the periodic system - they are neighbors and in many respects similar to each other. Active, typical metals, the atoms of which easily part with their only external electron, passing into the ionic state; these elements form numerous salts, widespread in nature. However, closer examination reveals that the biological functions of sodium and potassium are not the same. Potassium salts are better absorbed by the soil complex, so there is relatively more potassium in plant tissues, while sodium salts predominate in seawater. In biological machines, both of these ions sometimes act together, sometimes in exactly the opposite way.

Both ions take part in the propagation of electrical impulses along the nerve. In a resting nerve, in its inner part, a negative charge is concentrated (Fig. 20, a), and on the outer side there is a positive charge; the concentration of potassium ions is greater than the concentration of sodium ions inside the nerve. When irritated, the permeability of the nerve fiber membrane changes, and sodium ions rush into the nerve faster than potassium ions have time to leave (Fig. 20, b). As a result, a negative charge appears on the outside of the nerve fiber (there is not enough cations there), and a positive charge appears inside the nerve (where there is now an excess of cations) (Fig. 20, c). On the outer side of the fiber, diffusion of sodium ions begins to occur from neighboring areas to the one that is depleted in ions of this metal. Energetic diffusion leads to the appearance of a negative charge in neighboring areas (Fig. 20, d), and in the original area the original state is restored. Thus, the state of polarization (plus - inside, minus - outside) moved along the nerve fiber. Then all processes are repeated, and the nerve impulse spreads quite quickly throughout the nerve. Consequently, the mechanism of propagation of an electrical impulse along the nerve is due to the different permeability of the nerve fiber membrane with respect to sodium and potassium ions.

The question of the permeability of cell membranes to certain substances is extremely important. The passage of a substance through a biological membrane does not always resemble simple diffusion through a porous partition. For example, glucose and other carbohydrates pass through the red blood cell membrane using a special transporter that carries the molecules through the membrane. In this case, special conditions must be met - the carbohydrate molecule must have a certain shape, it must be curved so that its contour takes on the outline of a chair, otherwise the transfer may not take place. The concentration of carbohydrates in the external environment is greater than inside the erythrocyte, therefore this transfer is called passive.

There are cases when the membrane is tightly closed to certain ions: in particular, in mitochondria, the inner membrane does not allow potassium ions to pass through at all. However, these ions enter the mitochondria if the antibiotics valinomycin or gramicidin are present in the environment. Valinomycin specializes mainly in potassium ions (it can also transport rubidium and cesium ions), and gramicidin, in addition to potassium, also transports sodium, lithium, rubidium and cesium ions.

It was found that the molecules of such conductors have the shape of a steering wheel, the radius of the hole is such that an ion of potassium, sodium or other alkali metal is placed inside the steering wheel. These antibiotics were called ionophores ("ion carriers"). In Fig. Figure 21 shows diagrams of the transfer of ions through the membrane by valinomycin and gramicidin molecules. It is very likely that the toxic effect that antibiotics have on various microorganisms is precisely due to the fact that in their presence, the membranes begin to let in those ions that are not supposed to be there; this disrupts the functioning of the chemical systems of the microorganism cell and leads to its death or to serious disorders that stop its reproduction.

Active transport through membranes plays a significant role in biological machines (see Chapter 8). The question arises: where does the energy necessary for active transfer come from, and is it possible to carry it out without a special carrier?

As for energy, it is ultimately delivered by the same universal molecules ATP or creatine phosphate, the hydrolysis of which is accompanied by the release of large amounts of energy. But regarding carriers, the question is less clear, although there is no doubt that it is impossible to do without potassium and sodium metal ions.

The concentration of various substances in the cell (protein and mineral) is higher than in the environment; for this reason, most often the cell is under the threat of excessive penetration of water into it (as a result of osmosis). In order to get rid of this, the cell pumps sodium ions into the environment and thereby equalizes the osmotic pressure. For this reason, the concentration of sodium ions in the cell is less than in the environment. Here again the difference between sodium and potassium is revealed. Sodium is removed and the concentration of potassium ions is relatively higher inside the cell. Thus, a red blood cell contains approximately five times more potassium than sodium.

And the muscles have a high potassium content: per 100 g of raw muscle tissue there is 366 mg of potassium and 65 mg of sodium. Potassium in muscles facilitates the transition of the globular form of actin to the fibrillar form, which combines with myosin (see above).

There are some cases where an enzyme activated by potassium ions is inhibited by sodium ions, and vice versa. Therefore, the discovery of an enzyme whose action requires both ions attracted the attention of biochemists. This enzyme accelerates the hydrolysis of ATP and is called (K + Na) ATPase. To understand its role and mechanism of action, we must again turn to transfer processes.

As we have already indicated, the concentration of potassium ions inside the cells is increased, and there is relatively more sodium in the surrounding cellular environment. The pumping of sodium ions from the cell leads to an increased entry of potassium ions into the cell, as well as other substances (glucose, amino acids). Sodium and potassium ions can be exchanged according to the “ion for ion” principle, and then there is no potential difference on both sides of the cell membrane. But if there are more potassium ions inside the cell than sodium ions have left, a potential jump (about 100 mV) may occur; the sodium pumping system is called the "sodium pump". If a potential difference appears, then the term “electrogenic sodium pump” is used.

The introduction of large quantities of potassium ions into the cell turns out to be necessary, since potassium ions promote protein synthesis (in ribosomes) and also accelerate the process of glycolysis.

The cell membrane contains (K + Na) ATPase, a protein with a molecular weight of 670,000, which has not yet been separated from the membranes. This enzyme hydrolyzes ATP, and the energy from hydrolysis is used to transfer it in the direction of increasing concentration.

A remarkable property of (K + Na) ATPase is that, in the process of ATP hydrolysis, it is activated from inside the cell by sodium ions (and thereby ensures the excretion of sodium), and from outside the cell (from the environment) by potassium ions (facilitating their introduction into the cell) ; As a result, the distribution of ions of these metals necessary for the cell occurs. It is interesting to note that sodium ions in the cell cannot be replaced by any other ions. ATPase is activated internally only by sodium ions, but potassium ions acting externally can be replaced by rubidium or ammonium ions.

For the functions of individual organs, in particular the heart, not only the concentration of potassium, sodium, calcium and magnesium ions is important, but also their ratio, which must lie within certain limits. The ratio of the concentrations of these ions in human blood is not very different from the corresponding ratio characteristic of sea water. It is possible that biological evolution from the first forms of life that arose in the waters of the primordial ocean or on its shallows, to its highest forms, retained some chemical “imprints” of the distant past...

Returning to the beginning of this chapter, we again recall the multifunctionality of ions, their ability to perform a wide variety of duties in organisms. Calcium, sodium, potassium, and cobalt exhibit this ability in different ways. Cobalt forms a strong corrin-type complex, and this complex already catalyzes a variety of reactions. Calcium, sodium, potassium perform the functions of activators. But the magnesium ion can act both as an activator and as a component of a strong complex compound - chlorophyll, one of the most important compounds created by nature.

The outstanding scientist K. A. Timiryazev dedicated a work to chlorophyll, which he called “The Sun, Life and Chlorophyll,” indicating in it that it is chlorophyll that is the link that connects the processes of energy release on the Sun with life on Earth.

In the next chapter we will look at the properties of this interesting compound.