Cell membrane potential. Electrical phenomena in excitable cells
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! Up to 70% of the neuron’s total energy expenditure can be spent on the work of sodium-potassium pumps. This is 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 rectifying K+ current and of hyperpolarization in human myoblast fusion. Journal of Physiology 1998; 510: 467-76; differentiation of mesenchymal stem cells. Plos One 2008;
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 of 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 themselves 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
It has been established that the most important ions that determine the membrane potentials of cells are the inorganic ions K + , Na + , SG, and also, 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 the table 11.1 shows 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 ensured by both their different permeability and 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 from the Nernst-Planck equation it follows that
Thus, at rest the concentration gradients - and
electric potential - on the membrane directed
opposite to each other and therefore, in a resting cell, a high and constant difference in the concentrations of the main ions ensures the maintenance of an electrical voltage on the cell membrane, which is called equilibrium membrane potential.
In turn, the resting potential that arises on the membrane prevents the exit of K + ions from the cell and the excessive entry of SGs 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 it that for the resting membrane potential it is not the absolute values of the membrane permeabilities for various ions that are important, but their ratios, since by dividing both parts of the fraction under the logarithm sign, for example, by P k, we move on to the relative permeabilities of the ions.
In cases where the permeability of one of these ions is significantly greater than the others, equation (11.3) becomes the Nernst equation (11.1) for this ion.
From the table 11.1 shows 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 shows
The fact is that at rest the membrane is well permeable to K + and SG ions, while for Na + ions its permeability is very low.
Despite the fact that the equilibrium Nernst potential for SG is closest to the resting potential of the cell, the latter is predominantly potassium in nature. This is due to the fact that the high intracellular concentration of K + cannot significantly decrease, since K + ions must balance the volumetric negative charge of anions inside the cell. Intracellular anions are mainly large organic molecules (proteins, organic acid residues, etc.) that cannot pass through channels in the cell membrane. The concentration of these anions in the cell is almost 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 the cell does not have special mechanisms for maintaining the concentration of SG. Therefore, due to the negative charge of chlorine, its distribution turns out to be opposite to the distribution of potassium on the membrane (see Table 11.1). Thus, the concentration diffusions 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 influence 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 in the resting state, the permeability of the squid axon membrane for K + , Na + and SG is in the ratio 1: 0.04: 0.45. Thus, in a resting state, the cell membrane is poorly permeable only to Na +, and for SG it is permeable almost as well as for K +. In nerve cells, permeability for SG is usually lower than for K +, but in muscle fibers, permeability for SG is even somewhat predominant.
Despite the low permeability of the cell membrane to Na + at rest, there is, albeit very small, passive transfer of Na + into the cell. This Na + current would lead to a decrease in the potential difference across the membrane and to the release of K + from the cell, which would ultimately lead to an 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 (-bO)-(-100) mV. At first glance, it may seem that this is a small value, but we must take into account that the thickness of the membrane is also small (8-10 nm), so the electric field strength in the cell membrane is enormous 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 can. This is a normal condition for its operation, since it is precisely this 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 varies among cells, can change when the conditions of their life activity change. Thus, a disruption of bioenergetic processes in the cell, accompanied by a drop in the intracellular level of high-energy compounds (in particular, ATP), primarily eliminates the component of the resting potential associated with the work of Ma + -K + -ATPase.
Cell damage usually leads to an increase in the permeability of cell membranes, as a result of which the differences in membrane permeability for potassium and sodium ions decrease; the resting potential decreases, which can cause disruption 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 cell activity. Similar changes in the concentration of K in the blood plasma occur in some pathologies (for example, renal failure).
"Membrane potential"
Completed by Chetverikova R
1st year student
Faculty of Biology and Soils
Introduction
A little history
Electricity in the cage
Membrane potential
Action potential
Threshold of irritation
Characteristic properties of 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 “vital 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 can be unambiguously described except on the basis of the concepts of physics and chemistry. The development of molecular biology 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 developing. Erwin Schrödinger came to an optimistic, although 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 revealed in the future.
On the contrary, the development of biophysics as a part of modern physics testifies to its unlimited possibilities.
Using this example, we can clearly see how advances in physics have helped scientists understand such a complex phenomenon.
A little history
Man discovered electricity in living organisms in ancient times. Or rather, I felt it without suspecting its existence. This concept did not exist then. For example, the ancient Greeks were wary of meeting fish in the water, which, as the great scientist Aristotle wrote, “makes animals freeze.” The fish that terrified people was an electric stingray and was called “torpedo”. And only two hundred years ago scientists finally understood the nature of this phenomenon.
Scientists have long wanted to understand the nature of the signals flowing along the nerves. Among the many theories that arose in the middle of the 18th century, under the influence of the general fascination with electricity, a theory appeared that “electric fluid” was transmitted through the nerves.
The idea was in the air. Luigi Galvani, while 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, a muscle contraction occurred. Based on this, Galvani concludes that there is an electrical signal in a biological object. However, Galvani's contemporary Alessandro Volta ruled out a biological object and showed that an electric current could be generated by the contact of a set of metals separated by an electrolyte (voltaic column). This is how a chemical current source was discovered (named, however, later, in honor of its scientific opponent, a galvanic element).
This debate was the beginning of electrobiology. And now, half a century later, the German physiologist E. Dubois-Reymond confirmed Galvani's discovery, demonstrating the presence of electric fields in the nerves using improved electrical measuring equipment. The answer to the question of how electricity appears in a cell was found half a century later.
Electricity in the cage
In 1890, Wilhelm Ostwald, who worked on semi-permeable artificial films, suggested that semi-permeability could be the cause not only of osmosis, but also of electrical phenomena. Osmosis occurs when the membrane is selectively permeable, i.e. allows some particles to pass through and not others. Most often, the permeability of a membrane depends on the particle size. Ions can also be such particles. Then the membrane will allow ions of only one sign to pass through, for example, positive. Indeed, if you 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 not permeable to anions, that is, v = 0, then we can see, that large values for Vd should appear
(2)
Potential across a membrane separating two solutions
Thus, Ostwald combined Nernst's formula and knowledge of semi-permeable 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)
Membrane potential refers to the potential difference between the inner (cytoplasmic) and outer surfaces of the membrane
Using electrophysiological studies, it was proven 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, and 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 chlorine ions are 50 times lower. According to the laws of physics, if a living system were not regulated, 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 causes potassium to leave the cell and chlorine to enter the cell, resulting in an increase in the number of positive charges on the surface of the cell and a decrease in the number of charges inside the cell. Thus, a positive charge remains on the surface of the cell, and a negative charge inside. This distribution of electronic charges ensures that the membrane potential is maintained.
molecular biology membrane potential
Action potential
This leads to the accumulation of positive charges on the inner surface of the membrane, and negative charges 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 membrane potential, it is necessary to “pump out” sodium and potassium cations against the concentration gradient. This work is performed by the sodium-potassium pump, which restores the initial state of concentration of sodium and potassium cations, i.e. membrane potential is restored.
Threshold of irritation
For depolarization and subsequent excitation to occur, the stimulus must have a certain magnitude. The minimum strength of the current stimulus that can cause excitation is called the threshold of irritation. A value above the threshold is called superthreshold, and below the threshold is called subthreshold. Excitable formations obey the “all or nothing” law, which means that when irritation is applied at a force equal to the threshold, maximum excitation occurs. Irritation below the subthreshold strength does not cause irritation.
To characterize the strength of the current 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 stimulus of threshold strength will cause excitation only if this stimulus lasts for a certain time. The minimum current or excitation that must act on excitable formations to cause irritation is called rheobase. The minimum time during which a stimulus must act with the force of one rheobase in order to cause excitation is called the minimum useful time.
The magnitude of the irritation threshold depends not only on the duration of the current stimulus, but also on the steepness of the increase. When the rate of increase of the stimulus decreases below a certain value, excitation does not occur, no matter how strong we increase the stimulus. This happens because at the site of application of the stimulus the threshold constantly rises, and no matter what value the stimulus is brought to, excitation does not occur. This 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 increase in the stimulus.
The same law works not only for electrical stimulators, but also for others (chemical, mechanical stimuli/stimulants).
Characteristic properties of action potential
Polar law of irritation.
This law was first discovered by P.F. A weather vane. He established 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 it is closed under the cathode. This is due to the fact that the 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 stimulus of subthreshold strength does not cause excitation (nothing); at threshold stimulation, excitation takes on a maximum value (everything). A further increase in the strength of the stimulus does not increase arousal.
For a long time it was believed that this law was a general principle of excitable tissue. At the same time, it was believed that “nothing” is the complete absence of excitation, and “everything” is the complete manifestation of an excitable formation, i.e. his ability to excite.
However, with the help of microelectronic studies it has been proven that even under the action of a subthreshold stimulus in an excitable formation, redistribution of ions occurs between the outer and inner surfaces of the membrane. If, with the help of a pharmacological drug, the permeability of the membrane for sodium ions is increased or the permeability for potassium ions is reduced, then the amplitude of action potentials increases. Thus, we can conclude that this law should be considered only, as a rule, characterizing the features of an excitable formation.
Carrying out stimulation. 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. Signal transmission through such fibers is carried out using nodes of Ranvier. The signal passes through the myelinated areas, and thus, the conduction of excitation through them occurs faster than in non-myelinated areas; returning the impulse back is impossible, since the threshold of stimulation increases in the previous interception.
Excitability is the ability of a tissue to be irritated or excited and, therefore, to generate an action potential. The higher the threshold of irritation, the higher the arousal, and vice versa.
The value of the irritation threshold is inversely dependent on 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, and membrane potential are some of the most important aspects of modern biology.
The difference in electrical potential (in volts or mV) between the liquid on one side of the membrane and the liquid on the other side is called membrane potential(MP) and is designated Vm. The magnitude of the MF of living cells is usually from -30 to -100 mV and all this potential difference is created in the areas immediately adjacent to the cell membrane on both sides. A decrease in the magnitude of the MP is called depolarization, increase - hyperpolarization, restoration of the original value after depolarization - repolarization. Membrane potential exists in all cells, but in excitable tissues (nervous, muscle, glandular), membrane potential, or as it is also called in these tissues, resting membrane potential, plays a key role in the implementation of their physiological functions. The membrane potential is determined by two basic properties of all eukaryotic cells: 1) asymmetric distribution of ions between extra- and intracellular fluid, supported by metabolic processes; 2) Selective permeability of ion channels of cell membranes. To understand how MF occurs, let us imagine that a certain vessel is divided into two compartments by a membrane permeable only to potassium ions. Let the first compartment contain 0.1 M, and the second 0.01 M KCl solution. Since the concentration of potassium ions (K +) in the first compartment is 10 times higher than in the second, then at the initial moment for every 10 K + ions diffusing from compartment 1 to the second there will be one ion diffusing in the opposite direction. Since chlorine anions (Cl-) cannot pass through the membrane together with potassium cations, an excess of positively charged ions will form in the second compartment and, on the contrary, an excess of Cl- ions will appear in compartment 1. As a result, there is transmembrane potential difference, preventing further diffusion of K + into the second compartment, since for this they need to overcome the attraction of negative Cl- ions at the moment of entering the membrane from compartment 1 and the repulsion of like ions at the exit from the membrane into compartment 2. Thus, for each K ion + passing through the membrane at this moment, two forces act - a chemical concentration gradient (or a chemical potential difference), facilitating the transition of potassium ions from the first compartment to the second, and an electrical potential difference, causing the K + ions to move in the opposite direction. After these two forces are balanced, the number of K+ ions moving from compartment 1 to compartment 2 and back will be equal and established electrochemical equilibrium. The transmembrane potential difference corresponding to this state is called equilibrium potential, in this particular case, the equilibrium potential for potassium ions ( Ek). At the end of the 19th century, Walter Nernst established that the equilibrium potential depends on the absolute temperature, the valence of the diffusing ion and the ratio of the concentrations of this ion on different sides of the membrane:
Where Ex- equilibrium potential for ion X, R- universal gas constant = 1.987 cal/(mol deg), T- absolute temperature in degrees Kelvin, F- Faraday number = 23060 cal/v, Z- charge of the transferred ion, [X] 1 And [X] 2- ion concentration in compartments 1 and 2.
If we move from the natural logarithm to the decimal one, then for a temperature of 18˚C and a monovalent ion we can write the Nernst equation as follows:
Ex = 0.058 lg
Using the Nernst equation, we calculate the potassium equilibrium potential for an imaginary cell, assuming that the extracellular potassium concentration is [K + ]n = 0.01 M, and the intracellular potassium concentration is [K + ]v = 0.1 M:
Ek = 0.058 log = 0.058 log = 0.058 (-1) = -0.058 = -58 mv
In this case, Ek negative because potassium ions would leave the hypothetical cell, negatively charging the layer of cytoplasm adjacent to the inside of the membrane. Since there is only one diffusing ion in this hypothetical system, the potassium equilibrium potential will be equal to the membrane potential ( Ek= Vm).
The above mechanism is also responsible for the formation of the membrane potential in real cells, but unlike the simplified system considered, in which only one ion could diffuse through the “ideal” membrane, real cell membranes allow all inorganic ions to pass through in one way or another. However, the less permeable the membrane is to any ion, the less effect it has on the MP. Considering this circumstance, Goldman in 1943. an equation was proposed for calculating the value of the MF of real cells, taking into account the concentrations and relative permeability of all diffusing ions through the plasma membrane:
Vm = 0.058 lg
Using the labeled isotope method, Richard Keynes in 1954 determined the permeability of frog muscle cells to major ions. It turned out that the permeability for sodium is approximately 100 times less than for potassium, and the Cl- ion does not make any contribution to the creation of MP. Therefore, for muscle cell membranes, the Goldman equation can be written in the following simplified form:
Vm = 0.058 lg
Vm = 0.058 lg
Studies using microelectrodes inserted into cells have shown that the resting potential of frog skeletal muscle cells ranges from -90 to -100 mV. Such good agreement between experimental data and theoretical data confirms that the resting potential is determined by diffusion fluxes of inorganic ions. Moreover, in real cells the membrane potential is close to the equilibrium potential of the ion, which is characterized by maximum transmembrane permeability, namely the equilibrium potential of the potassium ion.
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 is a complex of active electrical, chemical and functional changes in excitable tissues (nervous, muscle 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 relative to its outer side. Between the outer surface of the cell, charged electropositively with respect 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 when the cell dies. L. Galvani showed back in 1794 that if you damage a nerve or muscle 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 a current that always flows from the undamaged part of the tissue to the site of the cut . He called this flow a quiescent current. In their physiological essence, resting current and resting membrane potential are one and the same. The potential difference measured in this experiment is 30-50 mV, since when tissue is damaged, part of the current is shunted into the intercellular space and the fluid surrounding the structure under study. The potential difference can be calculated using the Nernst formula:
where R is the gas constant, T is the absolute temperature, F is the Faraday number, [K] int. and [K] adv. - potassium concentration inside and outside the cell.
Rice. 2.1.
The cause 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 (ion 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 cell cytoplasm is poorer. Inside the cells there are 8-10 times less Na + ions and 50 times less C ions! ". The main cation of the cytoplasm is K +. Its concentration inside the cell is 30 times higher than in the extracellular environment, and is approximately equal to the extracellular concentration of Na. The main counterions for K + in the cytoplasm are organic anions, in particular the 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 must rush into it. is happening.
The first obstacle to equalizing the difference in ion concentrations is the plasma membrane of the cell. It consists of a double layer of phospholipid molecules, covered on the inside with a layer of protein molecules, and on the outside with a layer of carbohydrates (mucopolysaccharides). Some cellular proteins are embedded directly in 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. Protein channels, or pores, provide selective permeability (diffusion) through the membrane of ions and molecules corresponding to their size. Receptor proteins possessing 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 surface of the membrane. Structural proteins ensure the connection of cells into organs and the maintenance of subcellular structure.
All these proteins are specific, but not strictly. Under certain conditions, a particular protein can simultaneously be a pump, an enzyme, and a receptor. Through membrane channels, water molecules, as well as ions corresponding to the size of the pores, enter and exit the cell. The permeability of the membrane for different cations is not the same and changes under 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 approximately 20 times higher than potassium. At rest, equal concentrations of potassium in the cytoplasm and sodium in the extracellular environment should provide an equal number 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 in relation to the inner side of the membrane, near which negatively charged molecules of aspartic, histamine and others, too large for the pores of the membrane, increasingly accumulate amino acids that “release” potassium outside the cell, but “prevent” it from going far due to their negative charge. Negative charges accumulate on the inside of the membrane, and positive charges on the outside. A potential difference arises. 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 counter current of potassium ions. Sodium ions, penetrating into the cell, reduce the resting potential, allowing it to remain 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 per unit time from the cell outward, and positively charged sodium ions diffusing through the membrane in the opposite direction. The higher this ratio, the greater 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 is called sodium-potassium or ionic, since it actively removes (pumps out) sodium ions penetrating into it from the protoplasm and introduces (pumps) potassium ions into it. The source of energy 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 ATPase).
Rice. 2.2.
This is a large protein, exceeding the thickness of the cell membrane. The molecule of this protein, penetrating the membrane, binds predominantly sodium and ATP on the inside, and potassium and various inhibitors such as glycosides on the outside. In this case, a membrane current occurs. Thanks to this current, the appropriate direction of ion transport is ensured. Ion transfer occurs in three stages. First, the ion combines with a carrier molecule to form an ion-transporter complex. This complex then passes through the membrane or transfers 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 occurs, transporting ions in the opposite direction. If the pump transfers one sodium ion to one potassium ion, then it simply maintains a 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 transport sodium and potassium in a ratio of 3:2, i.e., for every 2 potassium ions entering the cell, it must remove 3 sodium ions from the cell. Working at maximum load, each pump is capable of pumping about 130 potassium ions and 200 sodium ions per second through the membrane. This is the maximum speed. In real conditions, the operation of each pump is adjusted according to the needs of the cell. Most neurons have between 100 and 200 ion pumps per square micron of membrane surface. Consequently, 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; accordingly, the activity of the pumps necessary 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 therefore on its functional purpose. Electrical polarization of the membrane is the main condition for cell excitability. This is her constant readiness for action. This is the cell's reserve of potential energy, which it can use in case the nervous system needs its immediate response.