": The resting potential is an important phenomenon in the life of all cells in the body, and it is important to know how it is formed. However, this is a complex dynamic process, difficult to comprehend in its entirety, especially for junior students (biological, medical and psychological specialties) and unprepared readers. However, when considered point by point, it is quite possible to understand its main details and stages. The work introduces the concept of the resting potential and highlights the main stages of its formation using figurative metaphors that help to understand and remember the molecular mechanisms of the formation of the resting potential.
Membrane transport structures - sodium-potassium pumps - create the prerequisites for the emergence of a resting potential. These prerequisites are the difference in ion concentration on the inner and outer sides of the cell membrane. The difference in sodium concentration and the difference in potassium concentration manifest itself separately. An attempt by potassium ions (K+) to equalize their concentration on both sides of the membrane leads to its leakage from the cell and the loss of positive electrical charges along with them, due to which the overall negative charge of the inner surface of the cell is significantly increased. This "potassium" negativity constitutes the majority of the resting potential (−60 mV on average), and a smaller portion (−10 mV) is the "exchange" negativity caused by the electrogenicity of the ion exchange pump itself.
Let's take a closer look.
Why do we need to know what resting potential is and how it arises?
Do you know what “animal electricity” is? Where do “biocurrents” come from in the body? How can a living cell located in an aquatic environment turn into an “electric battery” and why does it not immediately discharge?
These questions can only be answered if we know how the cell creates its electrical potential difference (resting potential) across the membrane.
It is quite obvious that in order to understand how the nervous system works, it is necessary to first understand how its individual nerve cell, the neuron, works. The main thing that underlies the work of a neuron is the movement of electrical charges through its membrane and, as a result, the appearance of electrical potentials on the membrane. We can say that a neuron, preparing for its nervous work, first stores energy in electrical form, and then uses it in the process of conducting and transmitting nervous excitation.
Thus, our very first step to studying the functioning of the nervous system is to understand how the electrical potential appears on the membrane of nerve cells. This is what we will do, and we will call this process formation of the resting potential.
Definition of the concept of “resting potential”
Normally, when a nerve cell is at physiological rest and ready to work, it has already experienced a redistribution of electrical charges between the inner and outer sides of the membrane. Due to this, an electric field arose, and an electric potential appeared on the membrane - resting membrane potential.
Thus, the membrane becomes polarized. This means that it has different electrical potentials on the outer and inner surfaces. The difference between these potentials is quite possible to register.
This can be verified if a microelectrode connected to a recording unit is inserted into the cell. As soon as the electrode gets inside the cell, it instantly acquires some constant electronegative potential with respect to the electrode located in the fluid surrounding the cell. The value of the intracellular electrical potential in nerve cells and fibers, for example, the giant nerve fibers of the squid, at rest is about −70 mV. This value is called the resting membrane potential (RMP). At all points of the axoplasm this potential is almost the same.
Nozdrachev A.D. and others. Beginnings of physiology.
A little more physics. Macroscopic physical bodies, as a rule, are electrically neutral, i.e. they contain both positive and negative charges in equal quantities. You can charge a body by creating an excess of charged particles of one type in it, for example, by friction against another body, in which an excess of charges of the opposite type is formed. Considering the presence of an elementary charge ( e), the total electric charge of any body can be represented as q= ±N× e, where N is an integer.
Resting potential- this is the difference in electrical potentials present on the inner and outer sides of the membrane when the cell is in a state of physiological rest. Its value is measured from inside the cell, it is negative and averages −70 mV (millivolts), although it can vary in different cells: from −35 mV to −90 mV.
It is important to consider that in the nervous system, electrical charges are not represented by electrons, as in ordinary metal wires, but by ions - chemical particles that have an electrical charge. In general, in aqueous solutions, it is not electrons, 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 only look positive on the outside, but on the inside they are negative.
The term “negativity,” which we will use to characterize the electrical potential inside the cell, will be useful to us to easily explain changes in the level of the resting potential. What is valuable about this term is that the following is intuitively clear: the greater the negativity inside the cell, the lower the potential is shifted to the negative side from zero, and the less negativity, the closer the negative potential is to zero. This is much easier to understand than to understand every time what exactly the expression “potential increases” means - an increase in absolute value (or “modulo”) will mean a shift of the resting potential down from zero, and simply an “increase” means a shift of the potential up to zero. The term "negativity" does not create such problems of ambiguity of understanding.
The essence of the formation of the resting potential
Let's try to figure out where the electric charge of nerve cells comes from, although no one rubs them, as physicists do in their experiments with electric charges.
Here one of the logical traps awaits the researcher and student: the internal negativity of the cell does not arise due to the appearance of extra negative particles(anions), but, on the contrary, due to loss of a certain amount of positive particles(cations)!
So where do positively charged particles go from the cell? Let me remind you that these are sodium ions - Na + - and potassium - K + that have left the cell and accumulated outside.
The main secret of the appearance of negativity inside the cell
Let’s immediately reveal this secret and say that the cell loses some of its positive particles and becomes negatively charged due to two processes:
- first, she exchanges “her” sodium for “foreign” potassium (yes, some positive ions for others, equally positive);
- 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:
- the cell's love for potassium (therefore the cell forcibly drags it towards itself);
- 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:
- Sodium (Na+) deficiency in the cell.
- Excess potassium (K+) in the cell.
- The appearance of a weak electric potential (−10 mV) on the membrane.
We can say this: at the first stage, membrane ion pumps create a difference in ion concentrations, or a concentration gradient (difference), between the intracellular and extracellular environment.
Second stage of creating negativity: leakage of K+ ions from the cell
So, what begins in the cell after its membrane sodium-potassium exchanger pumps work with ions?
Due to the resulting sodium deficiency inside the cell, this ion strives to rush inside: dissolved substances always strive to equalize their concentration throughout the entire volume of the solution. But sodium does this poorly, since sodium ion channels are usually closed and open only under certain conditions: under the influence of special substances (transmitters) or when the negativity in the cell decreases (membrane depolarization).
At the same time, there is an excess of potassium ions in the cell compared to the external environment - because the membrane pumps forcibly pumped it into the cell. And he, also trying to equalize his concentration inside and outside, strives, on the contrary, get out of the cage. And he succeeds!
Potassium ions K + leave the cell under the influence of a chemical gradient of their concentration on different sides of the membrane (the membrane is much more permeable to K + than to Na +) and carry away positive charges with them. Because of this, negativity grows inside the cell.
It is also important to understand that sodium and potassium ions do not seem to “notice” each other, they react only “to themselves.” Those. sodium reacts to the same sodium concentration, but “does not pay attention” to how much potassium is around. Conversely, potassium only responds to potassium concentrations and “ignores” sodium. It turns out that to understand the behavior of ions, it is necessary to separately consider the concentrations of sodium and potassium ions. Those. it is necessary to separately compare the concentration of sodium inside and outside the cell and separately - the concentration of potassium inside and outside the cell, but it makes no sense to compare sodium with potassium, as is sometimes done in textbooks.
According to the law of equalization of chemical concentrations, which operates in solutions, sodium “wants” to enter the cell from the outside; it is also drawn there by electrical force (as we remember, the cytoplasm is negatively charged). He wants to, but he can’t, since the membrane in its normal state does not allow him to pass through it well. Sodium ion channels present in the membrane are normally closed. If, nevertheless, a little of it comes in, then the cell immediately exchanges it for external potassium using its sodium-potassium exchanger pumps. It turns out that sodium ions pass through the cell as if in transit and do not stay in it. Therefore, sodium in neurons is always in short supply.
But potassium can easily leave the cell to the outside! The cage is full of him, and she can’t hold him. It exits through special channels in the membrane - "potassium leak channels", which are normally open and release potassium.
K + -leak channels are constantly open at normal values of the resting membrane potential and exhibit bursts of activity at shifts in membrane potential, which last several minutes and are observed at all potential values. An increase in K+ leakage currents leads to hyperpolarization of the membrane, while their suppression leads to depolarization. ...However, the existence of a channel mechanism responsible for leakage currents remained in question for a long time. Only now has it become clear that potassium leakage is a current through special potassium channels.
Zefirov A.L. and Sitdikova G.F. Ion channels of an excitable cell (structure, function, pathology).
From chemical to electrical
And now - once again the most important thing. We must consciously move away from movement chemical particles to the movement electric charges.
Potassium (K+) is positively charged, and therefore, when it leaves the cell, it carries out not only itself, but also a positive charge. Behind it, “minuses” - negative charges - stretch from inside the cell to the membrane. But they cannot leak through the membrane - unlike potassium ions - because... there are no suitable ion channels for them, and the membrane does not allow them to pass through. Remember about the −60 mV of negativity that remains unexplained by us? This is the very part of the resting membrane potential that is created by the leakage of potassium ions from the cell! And this is a large part of the resting potential.
There is even a special name for this component of the resting potential - concentration potential. Concentration potential - this is part of the resting potential created by the deficiency of positive charges inside the cell, formed due to the leakage of positive potassium ions from it.
Well, now a little physics, chemistry and mathematics for lovers of precision.
Electrical forces are related to chemical forces according to the Goldmann equation. Its special case is the simpler Nernst equation, the formula of which can be used to calculate the transmembrane diffusion potential difference based on different concentrations of ions of the same type on different sides of the membrane. So, knowing the concentration of potassium ions outside and inside the cell, we can calculate the potassium equilibrium potential E K:
Where E k - equilibrium potential, R- gas constant, T- absolute temperature, F- Faraday's constant, K + ext and K + int - concentrations of K + ions outside and inside the cell, respectively. The formula shows that to calculate the potential, the concentrations of ions of the same type - K + - are compared with each other.
More precisely, the final value of the total diffusion potential, which is created by the leakage of several types of ions, is calculated using the Goldman-Hodgkin-Katz formula. It takes into account that the resting potential depends on three factors: (1) the polarity of the electric charge of each ion; (2) membrane permeability R for each ion; (3) [concentrations of the corresponding ions] inside (internal) and outside the membrane (external). For the squid axon membrane at rest, the conductance ratio R K: PNa :P Cl = 1: 0.04: 0.45.
Conclusion
So, the resting potential consists of two parts:
- −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).
- 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
- 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;
- 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;
- Sarah Sundelacruz, Michael Levin, David L. Kaplan. (2008). Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells. PLoS ONE. 3 , e3737;
- 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;
- 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.;
- Makarov A.M. and Luneva L.A. Fundamentals of electromagnetism / Physics at a technical university. T. 3;
- Zefirov A.L. and Sitdikova G.F. Ion channels of an excitable cell (structure, function, pathology). Kazan: Art Cafe, 2010. - 271 p.;
- Rodina T.G. Sensory analysis of food products. Textbook for university students. M.: Academy, 2004. - 208 pp.;
- Kolman, J. and Rehm, K.-G. Visual biochemistry. M.: Mir, 2004. - 469 pp.;
- Shulgovsky V.V. Fundamentals of neurophysiology: A textbook for university students. M.: Aspect Press, 2000. - 277 pp..
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 a cell of excitable tissue, the resting potential. Since the inner side of the membrane is negatively charged relative to the outer one, taking the potential of the outer 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 emergence and maintenance of membrane potential was developed by Yu. Bernstein (1902). Based on the fact that the cell membrane has high permeability for potassium ions and 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 the modern membrane-ion 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 to 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 chlorine ions than extracellular fluid. The permeability of the membrane to ions is due to ion channels, protein macromolecules that penetrate the lipid layer. Some channels are constantly open, 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 channels. 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 membrane potential is 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 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, large molecular compounds for which the cell membrane is impermeable, create 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 it comes out and the higher the MP values. The passage of potassium and sodium ions through the membrane along their concentration gradient would ultimately 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 the cell membrane contains sodium-potassium pumps, 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 MP, since per unit time more sodium ions are removed from the cell than potassium is introduced (in a ratio of 3:2), which ensures a constant flow of positive ions from the cell. The fact that sodium excretion depends on the availability of metabolic energy is proven by the fact that under the influence of dinitrophenol, which blocks metabolic processes, sodium output is reduced by about 100 times. Thus, the emergence and maintenance of membrane potential is due to the selective permeability of the cell membrane and the operation of the sodium-potassium pump.
Why do we need to know what resting potential is?
What is "animal electricity"? Where do “biocurrents” come from in the body? How can a living cell in an aquatic environment turn into an “electric battery”?
We can answer these questions if we find out how the cell, due to redistributionelectric charges creates for himself electric potential on the membrane.
How does the nervous system work? Where does it all begin? Where does the electricity for nerve impulses come from?
We can also answer these questions if we find out how a nerve cell creates an electrical potential on its membrane.
So, understanding how the nervous system works begins with understanding how an individual nerve cell, a neuron, works.
And the basis for the work of a neuron with nerve impulses is redistributionelectric charges on its membrane and a change in the magnitude of electrical potentials. But in order to change the potential, you must first have it. Therefore, we can say that a neuron, preparing for its nervous work, creates an electrical potential, as an opportunity for such work.
Thus, our very first step to studying the work of the nervous system is to understand how electrical charges move on nerve cells and how, due to this, an electrical potential appears on the membrane. This is what we will do, and we will call this process of the appearance of electrical potential in neurons - resting potential formation.
Definition
Normally, when a cell is ready to work, it already has an electrical charge on the surface of the membrane. It is called resting membrane potential .
The resting potential is the difference in electrical potential between the inner and outer sides of the membrane when the cell is in a state of physiological rest. Its average value is -70 mV (millivolts).
"Potential" is an opportunity, it is akin to the concept of “potency”. The electrical potential of a membrane is its ability to move electrical charges, positive or negative. The charges are played by charged chemical particles - sodium and potassium ions, as well as calcium and chlorine. Of these, only chlorine ions are negatively charged (-), and the rest are positively charged (+).
Thus, having an electrical potential, the membrane can move the above charged ions into or out of the cell.
It is important to understand that in the nervous system, electrical charges are created not by electrons, as in metal wires, but by ions - chemical particles that have an electrical charge. Electric current in the body and its cells is a flow of ions, not electrons, as in wires. Note also that the membrane charge is measured from the inside cells, not outside.
To put it in a very primitive way, it turns out that “pluses” will predominate around the outside of the cell, i.e. positively charged ions, and inside there are “minus” signs, i.e. negatively charged ions. You could say there's a cage inside electronegative . And now we just need to explain how this happened. Although, of course, it is unpleasant to realize that all our cells are negative “characters”. ((
Essence
The essence of the resting potential is the predominance of negative electrical charges in the form of anions on the inner side of the membrane and the lack of positive electrical charges in the form of cations, which are concentrated on its outer side, and not on the inner.
Inside the cell there is “negativity”, and outside there is “positivity”.
This state of affairs is achieved through three phenomena: (1) the behavior of the membrane, (2) the behavior of the positive potassium and sodium ions, and (3) the relationship of chemical and electrical forces.
1. Membrane behavior
Three processes are important in the behavior of the membrane for the resting potential:
1) Exchange internal sodium ions to external potassium ions. Exchange is carried out by special membrane transport structures: ion exchanger pumps. In this way, the membrane oversaturates the cell with potassium, but depletes it with sodium.
2) Open potassium ion channels. Through them, potassium can both enter and exit the cell. It comes out mostly.
3) Closed sodium ion channels. Because of this, sodium removed from the cell by exchange pumps cannot return back to it. Sodium channels open only under special conditions - and then the resting potential is disrupted and shifted towards zero (this is called depolarization membranes, i.e. decreasing polarity).
2. Behavior of potassium and sodium ions
Potassium and sodium ions move through the membrane differently:
1) Through ion exchange pumps, sodium is forcibly removed from the cell, and potassium is dragged into the cell.
2) Through constantly open potassium channels, potassium leaves the cell, but can also return back into it through them.
3) Sodium “wants” to enter the cell, but “cannot”, because channels are closed to him.
3. Relationship between chemical and electrical force
In relation to potassium ions, an equilibrium is established between chemical and electrical forces at a level of - 70 mV.
1) Chemical the force pushes potassium out of the cell, but tends to pull sodium into it.
2) Electric the force tends to draw positively charged ions (both sodium and potassium) into the cell.
Formation of the resting potential
I’ll try to tell you briefly where the resting membrane potential in nerve cells—neurons—comes from. After all, as everyone now knows, our cells are only positive on the outside, but on the inside they are very negative, and in them there is an excess of negative particles - anions and a lack of positive particles - cations.
And here one of the logical traps awaits the researcher and student: the internal electronegativity of the cell does not arise due to the appearance of extra negative particles (anions), but, on the contrary, due to the loss of a certain number of positive particles (cations).
And therefore, the essence of our story will not lie in the fact that we will explain where the negative particles in the cell come from, but in the fact that we will explain how a deficiency of positively charged ions - cations - occurs in neurons.
Where do positively charged particles go from the cell? Let me remind you that these are sodium ions - Na + and potassium - K +.
Sodium-potassium pump
And the whole point is that in the membrane of a nerve cell they are constantly working exchanger pumps , formed by special proteins embedded in the membrane. What are they doing? They exchange the cell’s “own” sodium for external “foreign” potassium. Because of this, the cell ends up with a lack of sodium, which is used for metabolism. And at the same time, the cell is overflowing with potassium ions, which these molecular pumps brought into it.
To make it easier to remember, we can figuratively say this: " The cell loves potassium!"(Although there can be no talk of true love here!) That's why she drags potassium into herself, despite the fact that there is already plenty of it. Therefore, she unprofitably exchanges it for sodium, giving 3 sodium ions for 2 potassium ions. Therefore it spends ATP energy on this exchange. And how it spends it! Up to 70% of a neuron’s total energy expenditure 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 a cell is not born with a ready-made resting potential. For example, during differentiation and fusion of myoblasts, their membrane potential changes from -10 to -70 mV, i.e. their membrane becomes more electronegative and polarizes during differentiation. And in experiments on multipotent mesenchymal stromal cells (MMSC) from human bone marrow artificial depolarization inhibited differentiation cells (Fischer-Lougheed J., Liu J.H., Espinos E. et al. Human myoblast fusion requires expression of functional inward rectifier Kir2.1 channels. Journal of Cell Biology 2001; 153: 677-85; Liu J.H., Bijlenga P., Fischer-Lougheed J. et al. Role of an inward rectifier K+ current and of hyperpolarization in human myoblast fusion. Journal of Physiology 1998; 510: 467-76; Sundelacruz S., Levin M., Kaplan D. L. Membrane potential controls adipogenic and osteogenic differentiation of mesenchymal stem cells. Plos One 2008; 3).
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,
2) potassium’s love for freedom.
Oddly enough, the result of these two types of love is emptiness!
It is this emptiness that creates a negative electrical charge in the cell - the resting potential. More precisely, negative potential is createdempty spaces left by potassium that has escaped from the cell.
So, the result of the activity of membrane ion exchanger pumps is as follows:
The sodium-potassium ion exchanger pump creates three potentials (possibilities):
1. Electric potential - the ability to draw positively charged particles (ions) into the cell.
2. Sodium ion potential - the ability to draw sodium ions into the cell (and sodium ions, and not any others).
3. Ionic potassium potential - it is possible to push potassium ions out of the cell (and potassium ions, and not any others).
1. Sodium (Na +) deficiency in the cell.
2. Excess potassium (K+) in the cell.
We can say this: membrane ion pumps create concentration difference ions, or gradient (difference) concentration, between the intracellular and extracellular environment.
It is because of the resulting sodium deficiency that this same sodium will now “enter” the cell from the outside. This is how substances always behave: they strive to equalize their concentration throughout the entire volume of the solution.
And at the same time, the cell has an excess of potassium ions compared to the external environment. Because the membrane pumps pumped it into the cell. And he strives to equalize his concentration inside and outside, and therefore strives to leave the cell.
Here 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 reacts only to potassium concentrations and “ignores” sodium. It turns out that to understand the behavior of ions in a cell, it is necessary to separately compare 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 often done in textbooks.
According to the law of equalization of concentrations, which operates in solutions, sodium “wants” to enter the cell from the outside. But it cannot, since the membrane in its normal state does not allow it to pass through well. It comes in a little and the cell again immediately exchanges it for external potassium. 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. So it comes out through special protein holes in the membrane (ion channels).
Analysis
From chemical to electrical
And now - most importantly, follow the thought being expressed! We must move from the movement of chemical particles to the movement of electrical charges.
Potassium is charged with a positive charge, and therefore, when it leaves the cell, it takes out not only itself, but also “pluses” (positive charges). In their place, “minuses” (negative charges) remain in the cell. This is the resting membrane potential!
The resting membrane potential is a deficiency of positive charges inside the cell, formed due to the leakage of positive potassium ions from the cell.
Conclusion
Rice. Scheme of resting potential (RP) formation. The author thanks Ekaterina Yuryevna Popova for her help in creating the drawing.
Components of the resting potential
The resting potential is negative from the side of the cell and consists of two parts.
1. The first part is approximately -10 millivolts, which are obtained from the uneven operation of the membrane pump-exchanger (after all, it pumps out more “pluses” with sodium than it pumps back with potassium).
2. The second part is potassium leaking out of the cell all the time, dragging positive charges out of the cell. It provides most of the membrane potential, bringing it down to -70 millivolts.
Potassium will stop leaving the cell (more precisely, its input and output will be equal) only at a cell electronegativity level of -90 millivolts. But this is hampered by sodium constantly leaking into the cell, which carries its positive charges with it. And the cell maintains an equilibrium state at a level of -70 millivolts.
Please note that energy is required to create a resting potential. These costs are produced by ion pumps, which exchange “their” internal sodium (Na + ions) for “foreign” external potassium (K +). Let us remember that ion pumps are ATPase enzymes and break down ATP, receiving energy from it for the indicated exchange of ions of different types with each other. It is very important to understand that 2 potentials “work” with the membrane at once: chemical (concentration gradient of ions) and electrical ( difference in electrical potential on opposite sides of the membrane). Ions move in one direction or another under the influence of both of these forces, on which energy is wasted. In this case, one of the two potentials (chemical or electrical) decreases, and the other increases. Of course, if we consider the electric potential (potential difference) separately, then the “chemical” forces that move ions will not be taken into account. And then you may get the wrong impression that the energy for the movement of the ion comes from nowhere. But that's not true. Both forces must be considered: chemical and electrical. In this case, large molecules with negative charges located inside the cell play the role of “extras”, because they are not moved across the membrane by either chemical or electrical forces. Therefore, these negative particles are usually not considered, although they exist and they provide the negative side of the potential difference between the inner and outer sides of the membrane. But the nimble potassium ions are precisely capable of movement, and it is their leakage from the cell under the influence of chemical forces that creates the lion's share of the electrical potential (potential difference). After all, it is potassium ions that move positive electrical charges to the outside of the membrane, being positively charged particles.
So it’s all about the sodium-potassium membrane exchange pump and the subsequent leakage of “extra” potassium from the cell. Due to the loss of positive charges during this outflow, electronegativity inside the cell increases. This is the “resting membrane potential”. It is measured inside the cell and is typically -70 mV.
conclusions
Figuratively speaking, “the membrane turns the cell into an “electric battery” by controlling ionic flows.”
The resting membrane potential is formed due to two processes:
1. Operation of the sodium-potassium membrane pump.
The operation of the potassium-sodium pump, in turn, has 2 consequences:
1.1. Direct electrogenic (generating electrical phenomena) action of the ion exchanger pump. This is the creation of a small electronegativity inside the cell (-10 mV).
The unequal exchange of sodium for potassium is to blame for this. More sodium is released from the cell than potassium is exchanged. And along with sodium, more “pluses” (positive charges) are removed than are returned along with potassium. There is a slight deficiency of positive charges. The membrane is charged negatively from the inside (approximately -10 mV).
1.2. Creation of prerequisites for the emergence of high electronegativity.
These prerequisites are the unequal concentration of potassium ions inside and outside the cell. Excess potassium is ready to leave the cell and remove positive charges from it. We will talk about this below now.
2. Leakage of potassium ions from the cell.
From a zone of increased concentration inside the cell, potassium ions move into a zone of low concentration outside, at the same time carrying out positive electrical charges. There is a strong deficiency of positive charges inside the cell. As a result, the membrane is additionally charged negatively from the inside (up to -70 mV).
The final
The potassium-sodium pump creates the prerequisites for the emergence of the resting potential. This is the difference in ion concentration between the internal and external environment of the cell. The difference in sodium concentration and the difference in potassium concentration manifest itself separately. The cell's attempt to equalize the concentration of ions with potassium leads to loss of potassium, loss of positive charges and generates electronegativity within the cell. This electronegativity makes up most of the resting potential. A smaller part of it is the direct electrogenicity of the ion pump, i.e. predominant losses of sodium during its exchange for potassium.
Video: Resting membrane potential
In 1786, Luigi Galvani, professor of anatomy at the University of Bologna, conducted a series of experiments that laid the foundation for targeted research in the field of bioelectric phenomena. In the first experiment, he suspended a preparation of the naked legs of a frog using a copper hook on an iron grate, and found that every time the muscles touched the grate, they contracted. Galvani suggested that muscle contractions in general are a consequence of the influence of “animal electricity” on them, the source of which is nerves and muscles. However, according to Volta, the cause of the contraction was the electric current that arose in the area of contact of dissimilar metals. Galvani conducted a second experiment in which the source of the current acting on the muscle was as if a nerve: the muscle contracted again. Thus, precise proof of the existence of “animal electricity” was obtained.
All cells have their own electrical charge, which is formed as a result of the unequal permeability of the membrane to different ions. Cells of excitable tissues (nervous, muscle, glandular) are distinguished by the fact that, under the influence of a stimulus, they change the permeability of their membrane for ions, as a result of which ions are very quickly transported according to an electrochemical gradient. This is the process of excitation. Its basis is the resting potential.
Resting potential
Resting potential is a relatively stable difference in electrical potential between the outer and inner sides of the cell membrane. Its value usually varies from -30 to -90 mV. The inner side of the membrane at rest is negatively charged, and the outer side is positively charged due to unequal concentrations of cations and anions inside and outside the cell.
Intra- and extracellular ion concentrations (mmol/l) in muscle cells of warm-blooded animals
The picture is similar in nerve cells. Thus, it is clear that the main role in creating a negative charge inside the cell is played by K + ions and high-molecular intracellular anions; they are mainly represented by protein molecules with negatively charged amino acids (glutamate, aspartate) and organic phosphates. These anions typically cannot be transported across the membrane, creating a permanent negative intracellular charge. At all points of the cell the negative charge is almost the same. The charge inside the cell is negative both absolutely (there are more anions than cations in the cytoplasm) and relative to the outer surface of the cell membrane. The absolute difference is small, but it is enough to create an electrical gradient.
The main ion ensuring the formation of the resting potential (RP) is K +. In a resting cell, a dynamic equilibrium is established between the number of incoming and outgoing K + ions. This equilibrium is established when the electrical gradient balances the concentration gradient. According to the concentration gradient created by ion pumps, K+ tends to leave the cell, but the negative charge inside the cell and the positive charge on the outer surface of the cell membrane prevent this (electrical gradient). In the case of equilibrium, an equilibrium potassium potential is established on the cell membrane.
The equilibrium potential for each ion can be calculated using the Nernst formula:
E ion =RT/ZF ln( o / i),
where E ion is the potential created by a given ion;
R – universal gas constant;
T – absolute temperature (273+37°C);
Z – ion valency;
F – Faraday constant (9.65·10 4);
O – ion concentration in the external environment;
I is the concentration of the ion inside the cell.
At a temperature of 37°C, the equilibrium potential for K + is -97 mV. However, the real PP is less - about -90 mV. This is explained by the fact that other ions also contribute to the formation of PP. In general, PP is the algebraic sum of the equilibrium potentials of all ions located inside and outside the cell, which also includes the values of the surface charges of the cell membrane itself.
The contribution of Na + and Cl - to the creation of PP is small, but, nevertheless, it takes place. At rest, Na+ entry into the cell is low (much lower than K+), but it reduces the membrane potential. The effect of Cl is opposite, since it is an anion. The negative intracellular charge prevents much Cl - from entering the cell, so Cl is primarily an extracellular anion. Both inside and outside the cell, Na + and Cl - neutralize each other, as a result of which their joint entry into the cell does not have a significant effect on the PP value.
The outer and inner sides of the membrane carry their own electrical charges, mostly with a negative sign. These are polar components of membrane molecules - glycolipids, phospholipids, glycoproteins. Ca 2+ , as an extracellular cation, interacts with external fixed negative charges, as well as with negative carboxyl groups of the interstitium, neutralizing them, which leads to an increase and stabilization of PP.
To create and maintain electrochemical gradients, constant operation of ion pumps is required. An ion pump is a transport system that provides ion transport against an electrochemical gradient, with direct energy consumption. Na + and K + gradients are maintained using a Na/K – pump. The coupling of Na + and K + transport reduces energy consumption by approximately 2 times. In general, energy expenditure on active transport is enormous: the Na/K pump alone consumes about 1/3 of the total energy expended by the body at rest. 1ATP provides one cycle of work - the transfer of 3Na + from the cell, and 2 K + into the cell. Asymmetric ion transport also contributes to the formation of an electrical gradient (approximately 5 - 10 mV).
The normal value of PP is a necessary condition for the occurrence of cell excitation, i.e. propagation of an action potential that initiates specific cell activity.
Action potential (AP)
AP is an electrophysiological process expressed in rapid fluctuations in membrane potential due to the specific movement of ions and capable of spreading without decrement over long distances. The AP amplitude ranges from 80 – 130 mV, the duration of the AP peak in the nerve fiber is 0.5 – 1 ms. The amplitude of the action potential does not depend on the strength of the stimulus. AP either does not occur at all if the irritation is subthreshold, or reaches a maximum value if the irritation is threshold or suprathreshold. The main thing in the occurrence of AP is the rapid transport of Na + into the cell, which first contributes to a decrease in the membrane potential, and then to a change in the negative charge inside the cell to positive.
The AP consists of 3 phases: depolarization, inversion, and repolarization.
1. Depolarization phase. When a depolarizing stimulus acts on a cell, the initial partial depolarization occurs without changing its permeability to ions (there is no movement of Na + into the cell, since fast voltage-sensitive channels for Na + are closed). Na + channels have an adjustable gating mechanism, which is located on the inner and outer sides of the membrane. There are activation gates (m – gate) and inactivation gates (h – gate). At rest, m means the gate is closed, and h means the gate is open. The membrane also contains K + channels, which have only one gate (activation gate), closed at rest.
When cell depolarization reaches a critical value (E cr - critical level of depolarization, CLD), which is usually equal to 50 mV, the permeability for Na + increases sharply - a large number of voltage-dependent m - gates of Na + channels opens. In 1 ms, up to 6000 ions enter the cell through 1 open Na + channel. The developing depolarization of the membrane causes an additional increase in its permeability to Na +, more and more m - gates of Na + channels open, so that the Na + current has the character of a regenerative process (reinforces itself). As soon as the PP becomes zero, the depolarization phase ends.
2.Inversion phase. The entry of Na + into the cell continues, because the m - gate Na + - channels are still open, so the charge inside the cell becomes positive, and outside - negative. Now the electrical gradient prevents Na+ from entering the cell, however, because the concentration gradient is stronger than the electrical gradient, Na+ still passes into the cell. At the moment when the AP reaches its maximum value, the h – gate of the Na + channels closes (these gates are sensitive to the amount of positive charge in the cell) and the flow of Na + into the cell stops. At the same time, the gates of the K + - channels open. K+ is transported out of the cell according to a chemical gradient (in the descending phase of inversion, also along an electrical gradient). The release of positive charges from the cell leads to a decrease in its charge. K+ can also leave the cell at low speed through uncontrolled K+ channels, which are always open. All processes considered are regenerative. The AP amplitude is the sum of the AP value and the inversion phase value. The inversion phase ends when the electrical potential returns to zero.
3.Repolarization phase. This is due to the fact that the permeability of the membrane for K + is still high, and it leaves the cell along the concentration gradient, despite the opposition of the electrical gradient (the cell inside again has a negative charge). The release of K+ is responsible for the entire descending part of the AP peak. Often, at the end of AP, a slowdown in repolarization is observed, which is associated with the closure of a significant part of the gate of K + - channels, as well as with an increase in the oppositely directed electrical gradient.
PP- this is the difference in electrical potential between the outer and inner sides.
The PP plays an important role in the life of the neuron itself and the organism as a whole. It forms the basis for processing information in a nerve cell, ensures regulation of the activity of internal organs and the musculoskeletal system by triggering processes of excitation and contraction in the muscle.
Reasons for the formation of PP is the unequal concentration of anions and cations inside and outside the cell.
Formation mechanism:
As soon as at least a little Na + appears in the cell, the potassium-sodium pump begins to operate. The pump begins to exchange its own internal Na + for external K +. Because of this, the cell becomes deficient in Na +, and the cell itself becomes overfilled with potassium ions. K+ begins to leave the cell, because there is an excess of it. In this case, there are more anions in the cell than cations and the cell becomes negatively charged.
13. Characteristics of the action potential and the mechanism of its occurrence.
PD is an electrical process expressed in the fluctuation of membrane potential as a result of the movement of ions into and out of the cell.
Provides signal transmission between nerve cells, between nerve centers and working organs.
The PD consists of three phases:
1. Depolarization (i.e. the disappearance of the cell charge - a decrease in the membrane potential to zero)
2. Inversion (change of cell charge to the opposite, when the inner side of the cell membrane is charged positively, and the outer side is negatively charged)
3. Repolarization (restoration of the original charge of the cell, when the inner surface of the cell membrane is again charged negatively, and the outer surface – positively)
Mechanism of occurrence of PD: if the action of a stimulus on the cell membrane leads to the occurrence of PD, then the process of PD development itself causes phase changes in the permeability of the cell membrane, which ensures the rapid movement of the Na+ ion into the cell, and the K+ ion out of the cell.
14. Synaptic transmission to the central nervous system. Properties of synapses.
Synapse– the point of contact between a nerve cell and another neuron.
1.According to the transmission mechanism:
A. Electrical. In them, excitation is transmitted through an electric field. Therefore, it can be transmitted in both directions. There are few of them in the central nervous system.
b. Chemical. Excitation is transmitted through them using PAF, a neurotransmitter. They are the majority in the central nervous system.
V. Mixed.
2.By localization:
A. Axonodendritic
b. Axosomtic (axon + cell)
V. Axoaxonic
d. Dendrosomatic (dendrite + cell)
d. Dendrodendritic
3. By effect:
A. Exciting (triggering the generation of PD)
b. Inhibiting (preventing the occurrence of PD)
The synapse consists of:
Presynaptic terminal (axon terminal);
Synaptic cleft;
Postsynaptic part (end of dendrite);
Through the synapse, trophic influences are carried out, leading to changes in the metabolism of the innervated cell, its structure and function.
Properties of synapses:
Lack of strong connection between axon and dendrite;
Low lability;
Increased dysfunction;
Transformation of the rhythm of excitation;
Excitation transmission mechanism;
One-sided conduction of excitation;
High sensitivity to drugs and poisons;