"Membrane Potential"

Made by Chetverikova R

1st year student

Faculty of Biology and Soil

Introduction

A bit of history

Electricity in a cage

Membrane potential

action potential

Irritation threshold

Characteristic properties of the action potential

Conclusion

Introduction

Modern science is developing rapidly, and the more we move along the path of progress, the more we are convinced that in order to solve any scientific problems, it is necessary to combine the efforts and achievements of several branches of science at once.

Previously, the concept of vitalism dominated, according to which biological phenomena are fundamentally incomprehensible on the basis of physics and chemistry, since there is a certain “life force”, or entelechy, that is not subject to physical interpretation. In the 20th century, the great physicist Bohr considered the problem of the relationship between biology and physics based on the concept of complementarity, a special case of which is the uncertainty principle of quantum mechanics.

Bohr believed that not a single result of biological research could be unambiguously described except on the basis of the concepts of physics and chemistry. The development of molecular biology has led to an atomistic interpretation of the basic phenomena of life - such as heredity and variability. In recent decades, the physical theory of integral biological systems, based on the ideas of synergetics, has also been successfully developed. Erwin Schrödinger came to an optimistic, though not entirely reassuring conclusion: "Although modern physics and chemistry cannot explain the processes occurring in a living organism, there is no reason to doubt the possibility of their scientific explanation." Today there is every reason to assert that modern physics does not meet the limits of its applicability to the consideration of biological phenomena. It is difficult to think that such boundaries will be found in the future.

On the contrary, the development of biophysics as a part of modern physics testifies to its unlimited possibilities.

In this example, one can clearly see how the achievements of physics helped scientists understand such a complex phenomenon.

A bit of history

Man discovered electricity in living organisms in ancient times. Or rather, I felt it, unaware of its existence. This concept did not exist then. For example, the ancient Greeks were wary of meeting in the water with fish, which, as the great scientist Aristotle wrote, "makes animals numb." The fish that instilled fear in people was an electric stingray and bore the name "torpedo". And only two hundred years ago, scientists finally understood the nature of this phenomenon.

Scientists have long wanted to understand what is the nature of the signals flowing through the nerves. Among the many theories that arose in the middle of the 18th century, under the influence of the general enthusiasm for electricity, there appeared the theory that "electric fluid" is transmitted through the nerves.

The idea was in the air. Luigi Galvani, studying lightning discharges, used a frog neuromuscular preparation. Hanging it on a copper hook on the balcony railing, Galvani noticed that when the frog's legs touched the iron railing, muscle contraction occurred. Based on this, Galvani concludes that an electrical signal exists in a biological object. However, Galvani's contemporary Alessandro Volta ruled out a biological object and showed that an electric current can be obtained by contacting a set of metals separated by an electrolyte (voltaic column). Thus, a chemical current source was discovered (named, however, later, in honor of its scientific opponent, a galvanic cell).

This controversy was the beginning of electrobiology. And now, half a century later, the German physiologist E. Dubois-Reymond confirmed Galvani's discovery by demonstrating the presence of electric fields in the nerves with the help of improved electrical measuring equipment. The answer to the question of how electricity appears in a cell was found half a century later.

Electricity in a cage

In 1890, Wilhelm Ostwald, who studied semi-permeable artificial films, suggested that semi-permeability could be the cause of not only osmosis, but also electrical phenomena. Osmosis occurs when the membrane is selectively permeable, i.e. passes some particles and does not pass others. Most often, the permeability of the membrane depends on the particle size. Ions can also be such particles. Then the membrane will pass ions of only one sign, for example, positive. Indeed, if we look at the Nernst formula for the diffusion potential Vd arising at the boundary of two solutions with electrolyte concentrations C1 and C2:

where u is the speed of the faster ion, v is the speed of the slower ion, R is the universal gas constant, F is the Faraday number, T is the temperature, and assuming that the membrane is impermeable to anions, i.e. v = 0, then one can see, that large values ​​for Vd should appear

(2)

Potential across a membrane separating two solutions

Thus, Ostwald combined the Nernst formula and the knowledge of semipermeable membranes. He suggested that the properties of such a membrane explained the potentials of muscles and nerves and the action of the electrical organs of fish.

Membrane potential (resting potential)

Under the membrane potential understand the potential difference between the inner (cytoplasmic) and outer surfaces of the membrane

With the help of electrophysiological studies, it was proved that in a state of physiological rest, there is a positive charge on the outer surface of the membrane, and a negative charge on the inner surface.

Julius Bernstein created a theory according to which the difference in charges is determined by the different concentrations of sodium, potassium, chlorine ions inside and outside the cell. Inside the cell, the concentration of potassium ions is 30-50 times higher, the concentration of sodium ions is 8-10 times lower, and the concentration of chloride ions is 50 times less. According to the laws of physics, if the living system were not regulated, then the concentration of these ions would be equal on both sides of the membrane and the membrane potential would disappear. But this does not happen, because The cell membrane is an active transport system. The membrane has special channels for one or another ion, each channel is specific and the transport of ions inside and outside the cell is largely active. In a state of relative physiological rest, sodium channels are closed, while potassium and chloride channels are open. This leads to the fact that potassium leaves the cell, and chlorine enters the cell, as a result of which the number of positive charges on the cell surface increases and the number of charges inside the cell decreases. Thus, a positive charge remains on the surface of the cell, and a negative one inside. This distribution of electronic charges ensures the preservation of the membrane potential.

molecular biology membrane potential

action potential

This leads to the fact that positive charges accumulate on the inner surface of the membrane, and negative charges accumulate on the outer surface. This redistribution of charges is called depolarization.

In this state, the cell membrane does not exist for long (0.1-5 m.s.). In order for a cell to become capable of excitation again, its membrane must repolarize, i.e. return to resting potential. To return the cell to the membrane potential, it is necessary to “pump out” the sodium and potassium cations against the concentration gradient. This work is performed by the sodium-potassium pump, which restores the initial state of the concentration of sodium and potassium cations, i.e. membrane potential is restored.

Irritation threshold

For the occurrence of depolarization and subsequent excitation, the stimulus must have a certain value. The minimum strength of the acting stimulus that can cause excitation is called the threshold of irritation. The value above the threshold is called superthreshold, and below the threshold - subthreshold. Excitable formations obey the “all or nothing” law, which means that when irritation is applied with a force equal to the threshold, maximum excitation occurs. Irritation below the subthreshold strength does not cause irritation.

To characterize the strength of the acting stimulus from the time of its action, a curve is drawn that reflects how long the threshold or superthreshold stimulus must act to cause excitation. The action of a threshold strength stimulus will cause excitation only if this stimulus will act for a certain time. The minimum current or excitation that must act on excitable formations in order to cause irritation is called the rheobase. The minimum time during which the stimulus with the force of one reobase must act in order to cause excitation is called the minimum useful time.

The value of the stimulation threshold depends not only on the duration of the current stimulus, but also on the steepness of the increase. When the steepness of the growth of the stimulus decreases below a certain value, no excitation occurs, no matter how strong we bring the stimulus. This is because at the site of application of the stimulus, the threshold constantly rises, and no matter how much the stimulus is brought to, excitation does not occur. Such a phenomenon, the adaptation of an excitable formation to a slowly increasing strength of the stimulus, is called accommodation.

Different excitable formations have different rates of accommodation, so the higher the rate of accommodation, the steeper the rise of the stimulus.

The same law works not only for electrical stimulators, but also for others (chemical, mechanical stimuli / stimulants).

Characteristic properties of the action potential

Polar law of irritation.

This law was first discovered by P.F. weather vane. He found that direct current has a polar effect on excitable tissue. This is expressed in the fact that at the moment of closing the circuit, excitation occurs only under the cathode, and at the moment of opening - under the anode. Moreover, under the anode, when the circuit is opened, the excitation is much higher than when the circuit is closed under the cathode. This is due to the fact that a positively charged electrode (anode) causes hyperpolarization of the membrane, when the surfaces touch the cathode (negatively charged), it causes depolarization.

The all-or-nothing law

According to this law, a subthreshold stimulus does not cause excitation (nothing); with threshold stimulation, excitation takes on a maximum value (all). A further increase in the strength of the stimulus does not increase excitation.

For a long time it was believed that this law is the general principle of excitable tissue. At the same time, it was believed that “nothing” is a complete absence of excitation, and “everything” is a complete manifestation of an excitable formation, i.e. his ability to excite.

However, with the help of microelectronic studies, it was proved that even under the action of a subthreshold stimulus in an excitable formation, ions are redistributed between the outer and inner surfaces of the membrane. If, with the help of a pharmacological preparation, the membrane permeability for sodium ions is increased or the permeability for potassium ions is reduced, then the amplitude of the action potentials increases. Thus, we can conclude that this law should be considered only, as a rule, characterizing the features of excitable education.

Carrying out excitation. Excitability.

In demyelinated and myelinated fibers, excitation is transmitted differently, this is due to the anatomical features of these fibers. Myelinated nerve fibers have nodes of Ranvier. Transmission of signals through such fibers is carried out using intercepts of Ranvier. The signal skips through the myelinated areas, and thus, the conduction of excitation through them occurs faster than in non-myelinated areas, the return of the impulse is impossible, since the threshold of irritation increases in the previous intercept.

Excitability is the ability to irritate or excite and, consequently, the occurrence of an action potential. The higher the threshold of irritation, the higher the excitation, and vice versa.

The value of the threshold of stimulation is inversely related to the duration (t) of the stimulus and the steepness of the increase in its strength

Thus, we see that without the help of physics it would not have been possible to discover the secret of electricity in living organisms, the transmission of nerve impulses, membrane potential - one of the most important aspects of modern biology.

»: Resting potential is an important phenomenon in the life of all body cells, and it is important to know how it is formed. However, this is a complex dynamic process, difficult to understand as a whole, especially for undergraduate students (biological, medical and psychological specialties) and unprepared readers. However, when considering the points, it is quite possible to understand its main details and stages. The paper 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 the concentration of ions on the inner and outer sides of the cell membrane. Separately, the difference in concentration for sodium and the difference in concentration for potassium manifest themselves. An attempt of 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 electric charges along with them, due to which the overall negative charge of the inner surface of the cell is significantly increased. This "potassium" negativity makes up most of the resting potential (−60 mV on average), and the smaller part (−10 mV) is the "exchange" negativity caused by the electrogenicity of the ion exchange pump itself.

Let's understand in more detail.

Why do we need to know what the 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 in an aquatic environment turn into an "electric battery" and why does it not instantly discharge?

These questions can only be answered if we find out how the cell creates for itself a difference in electrical potentials (resting potential) across the membrane.

It is quite obvious that in order to understand how the nervous system works, it is first necessary to understand how its separate 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 in studying the workings 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 resting potential formation.

Definition of the concept of "resting potential"

Normally, when a nerve cell is at physiological rest and ready to work, it has already undergone 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 is polarized. This means that it has a different electrical potential of the outer and inner surfaces. It is quite possible to register the difference between these potentials.

This can be verified by inserting a microelectrode connected to a recording device into the cell. As soon as the electrode enters the cell, it instantly acquires a certain 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, giant squid nerve fibers, at rest is about −70 mV. This value is called the resting membrane potential (RMP). At all points of the axoplasm, this potential is practically the same.

Nozdrachev A.D. etc. Beginnings of Physiology.

A little more physics. Macroscopic physical bodies are, as a rule, electrically neutral, i.e. they contain equal amounts of both positive and negative charges. It is possible to charge a body by creating in it an excess of charged particles of one type, for example, by friction against another body, in which an excess of charges of the opposite type is formed in this case. Taking into account 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 available 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, electric charges are not represented by electrons, as in ordinary metal wires, but by ions - chemical particles that have an electric charge. And in general, in aqueous solutions, not electrons, but ions move in the form of an electric current. Therefore, all electric currents in cells and their environment are ion currents.

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

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

The term "negativity", which we will use to characterize the electrical potential inside the cell, will be useful to us for the simplicity of explaining changes in the level of the resting potential. What is valuable in 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 smaller the 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 in the rest potential down from zero, but simply “increase” means a shift in potential up to zero. The term "negativity" does not create similar ambiguity problems.

The essence of resting potential formation

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 from the appearance of extra negative particles(anions), but, conversely, due to loss of some positive particles(cations)!

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

The main secret of the appearance of negativity inside the cell

Let's open this secret right away and say that the cell loses some of its positive particles and becomes negatively charged due to two processes:

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

These two processes we need to explain.

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

Protein proteins are constantly working in the membrane of the nerve cell. exchanger pumps(adenosine triphosphatase, or Na + /K + -ATPase), embedded in the membrane. They change the "own" sodium of the cell to the external "foreign" potassium.

But after all, when exchanging one positive charge (Na +) for another of the same positive charge (K +), there can be no shortage of positive charges in the cell! Correctly. But, nevertheless, because of 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 a 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 concentration of potassium 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.

What is important 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 inside the cell. (But remember that we still have to find an explanation for the remaining -60 mV!)

To make it easier to remember the operation of exchanger pumps, it can be figuratively expressed as follows: "The cell loves potassium!" Therefore, the cell drags potassium towards itself, despite the fact that it is already full of it. And therefore, she unprofitably exchanges it for sodium, giving 3 sodium ions for 2 potassium ions. And so it spends on this exchange the energy of ATP. And how to spend! Up to 70% of all neuron energy consumption can be spent on the work 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, the potential of their membrane changes from –10 to –70 mV, i.e. their membrane becomes more negative - it becomes polarized in the process of differentiation. And in experiments on multipotent mesenchymal stromal cells of the human bone marrow, artificial depolarization, which counteracts the resting potential and reduces cell negativity, even inhibited (depressed) cell differentiation.

Figuratively speaking, it can be expressed as follows: By creating the potential for rest, the cell is "charged with love." It's love for two things:

1. the love of the cell for potassium (therefore, the cell forcibly drags him to itself);
2. the love of potassium for freedom (therefore, potassium leaves the cell that has captured it).

We have already explained the mechanism of cell saturation with potassium (this is the work of exchange pumps), and we will explain the mechanism of potassium leaving the cell below, when we proceed to the description of 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 deficiency (Na +) in the cell.
2. Excess potassium (K +) in the cell.
3. Appearance of a weak electric potential on the membrane (–10 mV).

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

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

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

Due to the resulting sodium deficiency inside the cell, this ion strives at every opportunity rush inward: solutes always tend to equalize their concentration in the entire volume of the solution. But this does not work well for sodium, since sodium ion channels are usually closed and open only under certain conditions: under the influence of special substances (transmitters) or with a decrease in negativity in the cell (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 striving to equalize his concentration inside and outside, strives, on the contrary, get out of the cell. And he succeeds!

Potassium ions K + leave the cell under the action of a chemical concentration gradient on opposite 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.

Here it is also important to understand that sodium and potassium ions, as it were, "do not notice" each other, they react only "to themselves." Those. sodium reacts to the concentration of sodium, but "does not pay attention" to how much potassium is around. Conversely, potassium reacts only to the concentration of potassium and "does not notice" sodium. It turns out that in order to understand the behavior of ions, it is necessary to consider separately the concentrations of sodium and potassium ions. Those. it is necessary to separately compare the sodium concentration inside and outside the cell and separately the potassium concentration inside and outside the cell, but it makes no sense to compare sodium with potassium, as it happens in textbooks.

According to the law of equalization of chemical concentrations, which operates in solutions, sodium "wants" to enter the cell from the outside; the electric force also draws him there (as we remember, the cytoplasm is negatively charged). He wants to want something, but he cannot, since the membrane in its normal state does not pass it well. The sodium ion channels present in the membrane are normally closed. If, nevertheless, it enters a little, then the cell immediately exchanges it for external potassium with the help of its sodium-potassium exchange pumps. It turns out that sodium ions pass through the cell as if in transit and do not linger in it. Therefore, sodium in neurons is always in short supply.

But potassium just can easily go out of the cell! The cage is full of him, and she can't keep 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 show bursts of activity during membrane potential shifts that last several minutes and are observed at all potential values. An increase in K + leakage currents leads to membrane hyperpolarization, 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 it has 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 from movement chemical particles to the movement electric charges.

Potassium (K +) is positively charged, and therefore, when it leaves the cell, it takes out of it not only itself, but also a positive charge. Behind him from the inside of the cell to the membrane stretch "minuses" - negative charges. But they cannot seep through the membrane - unlike potassium ions - because. there are no suitable ion channels for them, and the membrane does not let them through. Remember the -60 mV negativity that we didn't explain? This is the very part of the resting membrane potential, which is created by the leakage of potassium ions from the cell! And that's a big 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 deficit 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 accuracy.

Electrical forces are related to chemical forces by the Goldman equation. Its particular case is the simpler Nernst equation, which can be used to calculate the transmembrane diffusion potential difference based on different concentrations of ions of the same species 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 is the gas constant, T is the absolute temperature, F- Faraday's constant, K + ext and K + ext - concentrations of ions K + 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 (int) and outside the membrane (ex). For the squid axon membrane at rest, the conductance ratio is R K: PNa :P Cl = 1:0.04:0.45.

Conclusion

So, the rest potential consists of two parts:

1. −10 mV, which are obtained from the “asymmetric” operation of the membrane exchanger pump (after all, it pumps out more positive charges (Na +) from 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 contribution is the main one: −60 mV. In sum, 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 negativity level of −90 mV. In this case, the chemical and electrical forces will equalize, pushing potassium through the membrane, but directing it in opposite directions. But this is hindered 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 equilibrium state at the level of −70 mV is maintained in the cell.

Now the resting membrane potential is finally formed.

Scheme of Na + /K + -ATPase clearly illustrates the "asymmetric" exchange of Na + for K +: pumping out excess "plus" in each cycle of the enzyme operation leads to a negative charge of the inner surface of the membrane. What this video does not say is that ATPase is responsible for less than 20% of the resting potential (−10 mV): the remaining "negativity" (−60 mV) comes from leaving the cell through the "potassium leak channels" of K ions + , striving 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. St. Petersburg: St. Petersburg State Electrotechnical University;
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6. Makarov A.M. and Luneva L.A. Fundamentals of electromagnetism / Physics at the Technical University. T. 3;
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All living cells have the ability, under the influence of stimuli, to move from a state of physiological rest to a state of activity or excitation.

Excitation- this is a complex of active electrical, chemical and functional changes in excitable tissues (nervous, muscular or glandular), with which the tissue responds to external influences. An important role in excitation is played by electrical processes that ensure the conduction of excitation along nerve fibers and bring tissues into an active (working) state.

Membrane potential

Living cells have an important property: the inner surface of the cell is always negatively charged with respect to its outer side. Between the outer surface of the cell, charged electropositively in relation to the protoplasm, and the inner side of the cell membrane, there is a potential difference that ranges from 60-70 mV. According to P. G. Kostyuk (2001), in a nerve cell, this difference ranges from 30 to 70 mV. The potential difference between the outer and inner sides of the cell membrane is called membrane potential. or resting potential(Fig. 2.1).

The resting membrane potential is present on the membrane as long as the cell is alive and disappears with cell death. L. Galvani, back in 1794, showed that if a nerve or muscle is damaged by making a cross section and applying electrodes connected to a galvanometer to the damaged part and to the site of damage, the galvanometer will show the current that always flows from the undamaged part of the tissue to the incision site . He called this current the quiescent current. In their physiological essence, the resting current and the resting membrane potential are one and the same. The potential difference measured in this experiment is 30-50 mV, since in case of tissue damage, part of the current is shunted in the intercellular space and the fluid surrounding the structure under study. The potential difference can be calculated using the Nernst formula:

where R - gas constant, T - absolute temperature, F - Faraday number, [K] ext. and [K] adv. - the concentration of potassium inside and outside the cell.

Rice. 2.1.

The reason for the occurrence of the resting potential is common to all cells. Between the protoplasm of the cell and the extracellular environment there is an uneven distribution of ions (ionic asymmetry). The composition of human blood in terms of salt balance resembles the composition of ocean water. The extracellular environment in the central nervous system also contains a lot of sodium chloride. The ionic composition of the cytoplasm of cells is poorer. Inside the cells, there are 8-10 times less Na + ions and 50 times less C ions! ". The main cytoplasmic cation is K +. Its concentration inside the cell is 30 times higher than in the extracellular environment, and approximately equals the extracellular concentration of Na. The main counterions for K + in the cytoplasm are organic anions, in particular anions of aspartic, histamine and other amino acids.Such asymmetry is a violation of thermodynamic equilibrium.In order to restore it, potassium ions must gradually leave the cell, and sodium ions should strive into it.However, this is not happening.

The first obstacle to leveling the difference in ion concentrations is the plasma membrane of the cell. It consists of a double layer of phospholipid molecules, covered from the inside by a layer of protein molecules, and from the outside by a layer of carbohydrates (mucopolysaccharides). Some of the cellular proteins are built directly into the lipid bilayer. These are internal proteins.

Membrane proteins of all cells are divided into five classes: pumps, channels, receptors, enzymes and structural proteins. Pumps serve to move ions and molecules against concentration gradients, using metabolic energy for this. protein channels, or pores, provide selective permeability (diffusion) through the membrane of ions and molecules corresponding to them in size. receptor proteins, having high specificity, they recognize and bind, attaching to the membrane, many types of molecules necessary for the life of the cell at any given time. Enzymes accelerate the course of chemical reactions at the membrane surface. Structural proteins ensure the connection of cells into organs and the maintenance of the subcellular structure.

All of these proteins are specific, but not strictly. Under certain conditions, a particular protein can be both a pump, an enzyme, and a receptor at the same time. Through the channels of the membrane, water molecules, as well as ions corresponding to the size of the pores, enter and leave the cell. The permeability of the membrane for different cations is not the same and changes with different functional states of the tissue. At rest, the membrane is 25 times more permeable to potassium ions than to sodium ions, and when excited, sodium permeability is about 20 times higher than potassium. At rest, equal concentrations of potassium in the cytoplasm and sodium in the extracellular environment should provide an equal amount of positive charges on both sides of the membrane. But since the permeability for potassium ions is 25 times higher, potassium, leaving the cell, makes its surface more and more positively charged with respect to the inner side of the membrane, near which negatively charged molecules of aspartic, histamine and other molecules that are too large for membrane pores accumulate more and more. amino acids that “released” potassium outside the cell, but “not allowing” it to go far due to its negative charge. Negative charges accumulate on the inside of the membrane, and positive charges accumulate on the outside. There is a potential difference. The diffuse current of sodium ions into the protoplasm from the extracellular fluid keeps this difference at the level of 60-70 mV, preventing it from increasing. The diffuse current of sodium ions at rest is 25 times weaker than the countercurrent of potassium ions. Sodium ions, penetrating into the cell, reduce the value of the resting potential, allowing it to be held at a certain level. Thus, the value of the resting potential of muscle and nerve cells, as well as nerve fibers, is determined by the ratio of the number of positively charged potassium ions diffusing out of the cell per unit time and positively charged sodium ions diffusing through the membrane in the opposite direction. The higher this ratio, the greater the value of the resting potential, and vice versa.

The second obstacle that keeps the potential difference at a certain level is the sodium-potassium pump (Fig. 2.2). It was called sodium-potassium or ionic, since it actively removes (pumps out) sodium ions penetrating into it from the protoplasm and introduces (injects) potassium ions into it. The energy source for the operation of the ion pump is the breakdown of ATP (adenosine triphosphate), which occurs under the influence of the enzyme adenosine triphosphatase, localized in the cell membrane and activated by the same ions, i.e. potassium and sodium (sodium-potassium-dependent ATP-ase).

Rice. 2.2.

It is a large protein that is larger than the thickness of the cell membrane. The molecule of this protein, penetrating the membrane through, binds predominantly sodium and ATP on the inside, and potassium and various inhibitors such as glycosides on the outside. This creates a membrane current. Due to this current, the appropriate direction of ion transport is ensured. The transfer of ions occurs in three stages. First, an ion combines with a carrier molecule to form an ion-carrier complex. This complex then passes through the membrane or transfers a charge across it. Finally, the ion is released from the carrier on the opposite side of the membrane. At the same time, a similar process takes place, transporting ions in the opposite direction. If the pump transfers one sodium ion to one potassium ion, then it simply maintains the concentration gradient on both sides of the membrane, but does not contribute to the creation of the membrane potential. To make this contribution, the ion pump must transfer sodium and potassium in a ratio of 3:2, i.e., for 2 potassium ions entering the cell, it must remove 3 sodium ions from the cell. When operating at maximum load, each pump is capable of pumping about 130 potassium ions and 200 sodium ions through the membrane per second. This is the top speed. In real conditions, each pump is regulated according to the needs of the cell. Most neurons have 100 to 200 ion pumps per square micron of membrane surface. Therefore, the membrane of any nerve cell contains 1 million ion pumps capable of moving up to 200 million sodium ions per second.

Thus, the membrane potential (resting potential) is created as a result of both passive and active mechanisms. The degree of participation of certain mechanisms in different cells is not the same, which means that the membrane potential may be different in different structures. The activity of the pumps may depend on the diameter of the nerve fibers: the thinner the fiber, the higher the ratio of the surface size to the volume of the cytoplasm, respectively, and the activity of the pumps required to maintain the difference in ion concentrations on the surface and inside the fiber should be greater. In other words, the membrane potential may depend on the structure of the nervous tissue, and hence on its functional purpose. The electrical polarization of the membrane is the main condition that ensures cell excitability. This is her constant readiness for action. This is the cell's store of potential energy, which it can use in case the nervous system needs its immediate response.

Membrane potential

At rest, there is a potential difference between the outer and inner surfaces of the cell membrane, which is called the membrane potential [MP], or, if it is an excitable tissue cell, the resting potential. Since the inner side of the membrane is negatively charged with respect to the outer side, then, taking the potential of the external solution as zero, the MP is written with a minus sign. Its value in different cells ranges from minus 30 to minus 100 mV.

The first theory of the origin and maintenance of the membrane potential was developed by Yu. Bernshtein (1902). Based on the fact that the cell membrane has a high permeability for potassium ions and a low permeability for other ions, he showed that the value of the membrane potential can be determined using the Nernst formula.

In 1949–1952 A. Hodgkin, E. Huxley, B. Katz created a modern membrane-ionic theory, according to which the membrane potential is determined not only by the concentration of potassium ions, but also by sodium and chlorine, as well as by the unequal permeability of the cell membrane for these ions. The cytoplasm of nerve and muscle cells contains 30-50 times more potassium ions, 8-10 times less sodium ions, and 50 times less chloride ions than the extracellular fluid. Membrane permeability for ions is due to ion channels, protein macromolecules penetrating the lipid layer. Some channels are open all the time, others (voltage-dependent) open and close in response to changes in the magnetic field. Voltage-gated channels are divided into sodium, potassium, calcium and chloride. In a state of physiological rest, the membrane of nerve cells is 25 times more permeable to potassium ions than to sodium ions.

Thus, according to the updated membrane theory, the asymmetric distribution of ions on both sides of the membrane and the associated creation and maintenance of the membrane potential are due to both the selective permeability of the membrane for various ions and their concentration on both sides of the membrane, and more accurately, the value of the membrane potential can be calculated according to the formula.

Membrane polarization at rest is explained by the presence of open potassium channels and a transmembrane gradient of potassium concentrations, which leads to the release of part of the intracellular potassium into the environment surrounding the cell, i.e., to the appearance of a positive charge on the outer surface of the membrane. Organic anions are macromolecular compounds for which the cell membrane is impermeable, creating a negative charge on the inner surface of the membrane. Therefore, the greater the difference in potassium concentrations on both sides of the membrane, the more potassium is released and the higher the MP values. The transition of potassium and sodium ions through the membrane along their concentration gradient should eventually lead to equalization of the concentration of these ions inside the cell and in its environment. But this does not happen in living cells, since there are sodium-potassium pumps in the cell membrane, which ensure the removal of sodium ions from the cell and the introduction of potassium ions into it, working with the expenditure of energy. They also take a direct part in the creation of the MF, since more sodium ions are removed from the cell per unit time than potassium is introduced (at a ratio of 3:2), which ensures a constant current of positive ions from the cell. The fact that the excretion of sodium depends on the availability of metabolic energy is proved by the fact that under the action of dinitrophenol, which blocks metabolic processes, the sodium output decreases by about 100 times. Thus, the appearance and maintenance of the membrane potential is due to the selective permeability of the cell membrane and the operation of the sodium-potassium pump.

It has been established that the most important ions that determine the membrane potentials of cells are inorganic ions K + , Na + , SG, and in some cases Ca 2 + . It is well known that the concentrations of these ions in the cytoplasm and in the intercellular fluid differ tenfold.

From Table. 11.1 it can be seen that the concentration of K + ions inside the cell is 40-60 times higher than in the intercellular fluid, while for Na + and SG the distribution of concentrations is opposite. The uneven distribution of the concentrations of these ions on both sides of the membrane is provided both by their different permeability and by the strong electric field of the membrane, which is determined by its resting potential.

Indeed, at rest the total flux of ions through the membrane is zero, and then it follows from the Nernst-Planck equation that

Thus, at rest concentration gradients - and

electric potential - directed at the membrane

opposite to each other and therefore, in a resting cell, a high and constant difference in the concentrations of the main ions ensures that an electrical voltage is maintained on the cell membrane, which is called equilibrium membrane potential.

In turn, the resting potential arising on the membrane prevents the release of ions from the K + cell and the excessive entry of SG into it, thereby maintaining their concentration gradients on the membrane.

A complete expression for the membrane potential, taking into account the diffusion fluxes of these three types of ions, was obtained by Goldman, Hodgkin and Katz:

where R k, P Na , P C1 - membrane permeability for the corresponding ions.

Equation (11.3) determines the resting membrane potentials of various cells with high accuracy. It follows from this that for the resting membrane potential, it is not the absolute values ​​of the membrane permeability for various ions that are important, but their ratios, since by dividing both parts of the fraction under the sign of the logarithm, for example, by P k, we will move on to the relative permeability of ions.

In cases where the permeability of one of these ions is much greater than the others, equation (11.3) goes into the Nernst equation (11.1) for this ion.

From Table. 11.1 it can be seen that the resting membrane potential of cells is close to the Nernst potential for K + and CB ions, but differs significantly from it in Na +. This testifies

The fact that at rest the membrane is well permeable to K + and SG ions, while its permeability to Na + ions is very low.

Despite the fact that the equilibrium Nernst potential for SG is closest to the resting potential of the cell, the latter has a predominantly potassium nature. This is due to the fact that a high intracellular concentration of K + cannot decrease significantly, since K + ions must balance the volume negative charge of anions inside the cell. Intracellular anions are mainly large organic molecules (proteins, organic acid residues, etc.) that cannot pass through the channels in the cell membrane. The concentration of these anions in the cell is practically constant and their total negative charge prevents a significant release of potassium from the cell, maintaining its high intracellular concentration together with the Na-K pump. However, the main role in the initial establishment of a high concentration of potassium ions and a low concentration of sodium ions inside the cell belongs to the Na-K pump.

The distribution of C1 ions is established in accordance with the membrane potential, since there are no special mechanisms in the cell to maintain the concentration of SG. Therefore, due to the negative charge of chlorine, its distribution is reversed with respect to the distribution of potassium on the membrane (see Table 11.1). Thus, the concentration diffusion of K + from the cell and C1 into the cell are practically balanced by the resting membrane potential of the cell.

As for Na + , at rest its diffusion is directed into the cell under the action of both the concentration gradient and the electric field of the membrane, and the entry of Na + into the cell is limited at rest only by the low permeability of the membrane for sodium (sodium channels are closed). Indeed, Hodgkin and Katz experimentally established that at rest the permeability of the squid axon membrane for K + , Na + and SG is related as 1: 0.04: 0.45. Thus, at rest, the cell membrane is poorly permeable only for Na + , and for SG it is permeable almost as well as for K + . In nerve cells, the permeability for SG is usually lower than for K + , but in muscle fibers, the permeability for SG even somewhat predominates.

Despite the low permeability of the cell membrane for Na + at rest, there is, albeit a very small, passive transfer of Na + into the cell. This current of Na + should have led to a decrease in the potential difference across the membrane and to the release of K + from the cell, which would eventually lead to equalization of the concentrations of Na + and K + on both sides of the membrane. This does not happen due to the operation of the Na + - K + pump, which compensates for the leakage currents of Na + and K + and thus maintains the normal values ​​of the intracellular concentrations of these ions and, consequently, the normal value of the resting potential of the cell.

For most cells, the resting membrane potential is (-60) - (-100) mV. At first glance it may seem that this is a small value, but it must be taken into account that the membrane thickness is also small (8-10 nm), so the electric field strength in the cell membrane is huge and amounts to about 10 million volts per 1 m (or 100 kV per 1 cm):

Air, for example, cannot withstand such an electric field strength (electrical breakdown in air occurs at 30 kV/cm), but the membrane does. This is a normal condition for its activity, since it is precisely such an electric field that is necessary to maintain the difference in the concentrations of sodium, potassium and chlorine ions on the membrane.

The value of the resting potential, which is different in cells, can change when the conditions of their life activity change. Thus, the violation of bioenergetic processes in the cell, accompanied by a drop in the intracellular level of macroergic compounds (in particular, ATP), primarily excludes the component of the resting potential associated with the work of Ma + -K + -ATPase.

Damage to the cell usually leads to an increase in the permeability of cell membranes, as a result of which the differences in the permeability of the membrane for potassium and sodium ions decrease; the resting potential at the same time decreases, which can cause a violation of a number of cell functions, such as excitability.

• Since the intracellular concentration of potassium is maintained almost constant, even relatively small changes in the extracellular concentration of K * can have a noticeable effect on the resting potential and on the activity of the cell. Similar changes in the concentration of K "in the blood plasma occur in some pathologies (for example, renal failure).