However, passive mechanisms do not allow us to understand the reasons for the persistence of ion asymmetry throughout the life of the cell; in addition, it was noted that many substances pass through the membrane against the concentration gradient. Naturally, this process requires energy. Therefore, this transfer mechanism is called active. Active transfer is always selective. It was discovered in 1955 by Hodgkin and named potassium-sodium pump.
It ensures the “pumping out” of sodium ions from the cell and the transport of potassium ions into it. This is accomplished with the help of a carrier protein. It captures 3 sodium ions in the cytoplasm of the cell and transports them outside, where the ions are split off and thus removed from the cell. On the outer surface, 2 potassium ions are attached to the carrier, which are pumped into the cell.
This work is carried out with the expenditure of energy, the source of which is adenosine triphosphate (ATP). The breakdown of ATP occurs under the action of the enzyme ATPase, which releases energy that is used in the operation of the potassium-sodium pump. With shifts in the transmembrane ion concentration, the activity of the K-Na pump can be automatically adjusted. In regulation, adenosine triphosphatase is of particular importance, which is activated by increasing the concentration of sodium in the cytoplasm and potassium in the intercellular fluid.
The operation of the pump leads to the following results:
1) maintains a high concentration of K + ions inside the cell, thereby ensuring a constant value of the resting potential,
2) maintains a low concentration of sodium ions inside the cell,
3) maintaining the sodium concentration gradient, the sodium-potassium pump promotes the coupled transport of amino acids and glucose across the cell membrane.
Thus, ionic asymmetry is due to both the selective permeability of the membrane at rest and the activity of the K-Na pump. This value can be calculated using the Goldman formula:
RTP K [K] B n +P N a B n +P Cl H
E m = ______ ln ________________________________________________, where
NFP K [K] B n +P N a B n +P Cl H
P K , P N a, P Cl – permeability for K, Na, Cl ions,
ext, n – their internal and external concentration.
Change in membrane potential. Action potential or action currents
Biocurrents are observed not only during rest, but also during tissue stimulation. Electrical processes always accompany excitation and are its best criterion.
The presence of biocurrents during excitation was first discovered by Matteuci in 1837 in the following experiment. He took 2 n.m. the drug and the nerve of one of them was applied to the muscle of the other, whose nerve was irritated by an electric current. when turning on El. current, not only the irritated muscle contracted, but also the other one. This fact is explained by the fact that when the first muscle contracts, biocurrents arise in it, the strength of which is sufficient to excite the nerve of the second drug lying on it and cause contraction of the innervated muscle.
In 1954, Müller and Kölliker established that electrical phenomena also accompany the activity of the heart. They applied the n.m. nerve to the contracting heart of a warm-blooded animal. a preparation of the frog gastrocnemius muscle and observed that with each contraction of the heart, the muscle also contracts simultaneously. The biocurrents of the heart excite the nerve, and it excites the muscle.
Subsequently, biocurrents were discovered in all excitable tissues during their activity. In 1800, Herman called the currents accompanying the excitation process potentials or action currents. This term is still used today, and action currents are considered the best indicator of tissue excitation.
Action currents can be registered.
This is done using the microelectrode method. One electrode is placed on the surface, and the microelectrode is inserted into the cell. In this case, registration occurs against the background of resting currents or membrane potential. Immediately after introducing the electrode into the cell, the oscilloscope records the presence of a resting potential, which is equal to 70 mV. If you then stimulate the cell with a suprathreshold stimulus acting near the extracellular electrode, the cell is excited and the oscilloscope records a single-phase action current curve, which reflects the rapid oscillation of the membrane potential. At the moment of excitation, the curve rises steeply, reaches 0 and then exceeds it. After this, the excitation leaves the point of influence and the membrane charge is restored to -70 mV.
In this case, a single-phase action potential (Fig.8) . There are several parts in the single-phase action current curve. The ascending part of the curve is called depolarization phase, since it reflects the process of decrease and disappearance of the initial polarization of the membrane. This phase occurs most quickly. The peak of the action current is called spike. The descending knee characterizes the restoration of the initial polarization of the membrane and is called repolarization phase. In this phase there are 2 parts - rapid repolarization with a steep drop in curve and slow, when the recovery of membrane potential slows down, This part is often called trace negative potential. After it, in some tissues (non-pulp nerves) there is trace positive potential, an increase in the membrane charge, its hyperpolarization.
The ionic mechanism of the action potential was first attempted to be explained by J. Bernshetein in 1912 from the position of the “ion barrier breakthrough theory.” According to this hypothesis, under the action of a stimulus, the membrane loses its selectivity and all ions are able to move along their concentration gradients: Na– into the cell, K– to the surface. Their concentration above and below the membrane is equalized and the membrane potential in the excited area disappears. This lasts for a very short time, after which the membrane potential is completely restored. According to Bernstein, the amplitude of action currents is equal to the value of the membrane potential.
This theory was extended prior to the microelectrode studies of Hodgkin and Katz (1949). In their experiments on giant squid nerve fibers, they found that action currents are larger than resting currents: when excited, the MP does not simply drop to 0, but changes to the opposite - the outer surface is charged negatively in relation to the inner one.
Hodgkin, Huxley, Katz (1952) first put forward a theory about the individual participation of various ions in the formation of the action potential (Fig. 9).
According to this theory, the action potential has several phases:
1) phase gradual depolarization – this is the time from the moment the stimulus is applied until the level of critical depolarization is reached, after which the high-amplitude part of the action potential develops. Gradual depolarization is characterized by the gradual opening of sodium channels, the slow entry of sodium ions into the cell along a concentration gradient, and a gradual decrease in MP. The duration of the first phase for nervous tissue is 0.00004 sec, for skeletal muscle – 0.0001 sec. When the membrane potential decreases to E cr, all sodium channels open and the next phase develops.
2) phase of rapid depolarization - this is the time of development of the peak from the beginning of its occurrence to the top. All sodium channels open, and sodium ions avalanchely enter the cell along the concentration and electrochemical gradient. During this phase, the membrane potential shifts rapidly, it decreases and acquires a positive charge, reaching a value of +30-+40 mV. It is called depolarization peak or spike. The amplitude of the action potential is 100-120 mV.
The duration of this phase for a nerve is approximately 0.001-0.002 seconds, for a muscle - approximately 0.005 seconds.
3) repolarization phase – is determined by the time of decrease in membrane polarization to the initial level. It starts when the membrane charge reaches +30-+40mV. At this point, sodium channels are inactivated and potassium channels are activated. Permeability for potassium ions increases and it begins to leave the cell. This period has two periods of time - a relatively rapid decrease in membrane polarization (fast repolarization) , and a subsequent slower decrease in cell polarization ( slow repolarization) which is called negative trace potential. The slow decrease in membrane polarization is due to the inclusion of active mechanisms for the transport of sodium and potassium ions (potassium-sodium pump). The duration of the third phase for a nerve is 0.02-0.03 seconds, for a muscle - approximately 0.05-0.1 seconds.
4) hyperpolarization phase (positive trace potential) – decrease in polarization of the cell membrane below the initial value. Hyperpolarization is characteristic of unmyelinated nerve fibers. It is associated with a temporarily increased permeability for K + ions. The duration of trace electropositivity for a nerve is approximately 0.1 sec, for a muscle – 0.25 sec or more.
After hyperpolarization, the MP is completely normalized to the original -70 mV. Similar APs are observed in any excitable system, proceeding at different speeds and taking different times. PD develops according to the “all or nothing” law.
Action currents serve as one of the most objective criteria of arousal, therefore their registration is used to assess the functioning of many organs: ECG, EEG, electromyography, etc. Action currents have found practical application in prosthetics - in the creation of controlled prostheses.
The mechanism of operation of the sodium-potassium pump. In one cycle, NCN transports 3 Na+ ions from the cell and 2 K+ ions into the cell. This is due to the fact that the integral protein molecule can be in 2 positions. The protein molecule that forms the channel has an active site that binds either Na+ or K+. In position (conformation) 1, it faces the inside of the cell and can accept Na+. The enzyme ATPase is activated, breaking down ATP to ADP. As a result, the molecule changes to conformation 2. In position 2, it faces outside the cell and can accept K+. Then the conformation changes again and the cycle repeats.
Ion channels
Ion channels are integral proteins that provide passive transport of ions along a concentration gradient. The energy for transport is the difference in ion concentration on both sides of the membrane (transmembrane ion gradient).
Non-selective channels have the following properties:
All types of ions pass through, but the permeability for K+ ions is significantly higher than for other ions;
are always open.
Selective channels have the following properties:
only one type of ion passes through; for each type of ion there is its own type of channel;
can be in one of 3 states: closed, activated, inactivated.
The selective permeability of the selective channel is ensured selective filter, which is formed by a ring of negatively charged oxygen atoms, which is located at the narrowest point of the channel.
Changing the channel state is ensured by the operation gate mechanism, which is represented by two protein molecules. These protein molecules, the so-called activation gate and inactivation gate, by changing their conformation, can block the ion channel.
In the resting state, the activation gate is closed, the inactivation gate is open (the channel is closed). When a signal acts on the gate system, the activation gate opens and ion transport through the channel begins (the channel is activated). With significant depolarization of the cell membrane, the inactivation gate closes and ion transport stops (the channel is inactivated). When the PP level is restored, the channel returns to its original (closed) state.
Depending on the signal that causes the activation gate to open, selective ion channels are divided into:
chemosensitive channels– the signal for the opening of the activation gate is a change in the conformation of the receptor protein associated with the channel as a result of the attachment of a ligand to it;
potential sensitive channels– the signal to open the activation gate is a decrease in PP (depolarization) of the cell membrane to a certain level, which is called critical level of depolarization(KUD).
Mechanism of action potential generation
When an electric current passes in the direction of polarization, the PP increases - this is the phenomenon of hyperpolarization. When the current passes in the opposite direction, the PP decreases - depolarization.
PP can only be reduced to a certain point. After the PP drops to 0, a change in polarity occurs, and a propagating electrical process occurs in the cell - an action potential (AP).
The membrane has many channels that allow ions to pass through. There are transport mechanisms: complexons, etc. But there is a channel that works against the electrical gradient - energy-consuming channels.
At a certain level, sodium channels open - a critical level of depolarization. It is 10-15% lower than the rest polarization level. These are voltage dependent channels. They, unlike potassium channels, which are always open, work only after a critical level of depolarization - the value of the membrane potential, upon reaching which AP occurs.
As soon as the channel opens, sodium ions rush into the cytoplasm of the neuron from the intercellular environment, of which there are approximately 50 times more than in the cytoplasm. This movement of ions is a consequence of a simple physical law: ions move along a concentration gradient. Thus, sodium ions enter the neuron; they are positively charged. In other words, an incoming current of sodium ions will flow through the membrane, which will shift the membrane potential towards depolarization, i.e., reduce the polarization of the membrane. The more sodium ions enter the cytoplasm of a neuron, the more its membrane is depolarized. The membrane potential will increase, opening more and more sodium channels. There are a lot of K+ and Na+ cations inside. But this potential will not grow indefinitely, but only until it becomes approximately +55 mV. This potential corresponds to the concentrations of sodium ions present in and outside the neuron, and is therefore called the sodium equilibrium potential. Recall that at rest the membrane had a potential of -70 mV, then the absolute amplitude of the potential will be about 125 mV.
Once sodium equilibrium is reached, the sodium channels are closed by a protein plug. This is the so-called “sodium inactivation”. The membrane becomes impermeable to sodium ions. In order for the membrane potential to return to its original resting state, it is necessary that a current of positive particles leaves the cell. This is where energy-consuming channels come to the rescue - the sodium-potassium pump. Additional energy is needed, which is obtained from the breakdown of 3-phosphate (ATP) to 2-phosphate (ADP). This system returns the cell to the original level of membrane polarization. These channels work all the time. Energy-consuming channels are potential independent. As a result of these processes, the neuron membrane returns to its resting state (-70 mV) and the neuron prepares for the next act of excitation.
The “all or nothing” rule: no matter how you influence the cell, it will not generate an AP until the level of depolarization is reached. If a cell creates an PD, then only the corresponding PP (PD is directly proportional to the PP). This rule only works outside the cage.
Trace processes: after a certain time after the generation of AP, no matter what you do with the cell, it will not be able to generate a new AP, since the initial level of depolarization has not yet been restored. This is a refractory period - the cell does not react to anything.
The sodium-potassium pump (or sodium-potassium pump) is probably one of the most studied proteins, but it continues to present surprises. Recently, a group of Danish researchers proposed a model for how this protein works, in which cytoplasmic protons play an important role. Some inherited neurological disorders, such as a type of hemiplegic migraine, appear to be caused by a mutation in the exact region of the pump where the proton binds.
Life originated in salty sea water, and the first cells - tiny bags with fresh contents - had to constantly “spit out” the sodium ions penetrating into them so as not to “salt”. Therefore, a special protein appeared in the cell membrane - a sodium-potassium pump. This transmembrane (that is, penetrating the membrane right through) protein pumps sodium ions out of the cell and in return lets in potassium ions: for every three sodium ions “spitted out”, two potassium ions are “swallowed” and one ATP molecule is broken down. The cell has learned to use the resulting chemical and electrical gradients to its advantage: for example, to create a resting potential, symport and maintain cellular volume.
The fact that in exchange for three sodium ions only two potassium ions enter the cell is a little alarming. If the pump has three sites for binding cations, where does one of them go when the protein transports potassium? A group of scientists from Denmark (the Danes are generally famous for their work in the biology of ion pumps, take, for example, the discoverer of the sodium pump, Jens Christian Skou) tried to prove that the place of the third sodium ion during potassium transfer is occupied by a cytoplasmic proton (that is, a hydrogen ion), which then, when becomes unnecessary and returns back to the cytoplasm. In addition, the researchers suggest that they have discovered a previously unexplored ion path in the sodium pump, along which this proton moves.
It all started when, while studying the alpha subunit of this protein, scientists noticed that between its C-terminus and the putative binding site for the third sodium ion there is a cavity lined with polar and charged amino acid residues - that is, an ideal path for ions. It is especially interesting that a severe hereditary disease - hemiplegic migraine - is caused by a mutation in amino acids located very close to this cavity.
To find out what this cavity is for, scientists tried to “spoil” it (by replacing some of the amino acids that form it with others) and see what problems the mutant protein would have. First, it turned out that the mutant pump had significantly lost its affinity for sodium. But in addition, it turned out that under certain conditions (at increased membrane potential) it “spitted out” sodium much more readily than the non-mutant protein. This could mean that a mutation in this part of the pump facilitates some process associated with the release of sodium.
The researchers conducted a series of other experiments and came to the conclusion that this mysterious process is the release of the C-terminus: it, like a cork, moves away from the main part of the protein, opens the ion channel and admits water molecules, which protonate the aspartate residue located in the depths (D930) . Sodium then leaves the pump and enters the extracellular space. All this allowed scientists to create an improved model of the sodium pump.
Apparently this is how it works. Let us first assume that three sodium ions “sit” in the pump at their binding sites and one proton on the glutamate residue. Sodium ions can exit into the extracellular space only when the C-terminus of the protein changes its position and ceases to plug the ion channel and water flows through this channel, which protonates the aspartate residue (where the binding site for sodium is located). When sodium ions enter the extracellular space, they are replaced by potassium ions. The proton that was on glutamate goes to aspartate, and the one that was on aspartate leaves the protein through an open ion channel. Potassium ions enter the intracellular space through one channel, and the proton, which was on aspartate, through another. Potassium ions are replaced by sodium ions. A proton “sits” on the glutamate residue, and the cycle repeats.
Active transport is the energy-consuming transfer of molecules or ions across a membrane against a concentration gradient. Energy is required because matter must move against its natural tendency to diffuse in the opposite direction. Movement is usually unidirectional, while diffusion is reversible. The source of energy for active transport is ATP, a compound formed during respiration and acting as an energy carrier in the cell. Therefore, in the absence of respiration, active transport cannot occur.
In extracellular and intracellular fluids, sodium ions (Na=), potassium ions (K+) and chloride ions (Cl-) predominate. The figure shows that the concentrations of these ions inside erythrocytes and in human blood plasma are very different. Inside red blood cells, as in most cells, the concentration of potassium is much higher than outside. Another characteristic feature is that the intracellular potassium concentration exceeds the sodium concentration.
If the respiration of red blood cells is suppressed by some specific influence, for example with cyanide, their ionic composition will begin to gradually change and will eventually become equal to the ionic composition of the blood plasma. This shows that these ions can passively diffuse through the plasma membrane of red blood cells, but that normally, due to the energy supplied by the respiration process, their active transport occurs, due to which the concentrations indicated in the figure are maintained. In other words, sodium is actively pumped out of the cell, and potassium is actively pumped into it.
Sodium-potassium pumpActive transport carried out using carrier proteins localized in the plasma membrane. These proteins, unlike those we discussed in our discussion of facilitated diffusion, require energy to change their conformation. This energy is supplied by ATP, which is produced during respiration.
Relatively recently, it became clear that most cells in the plasma membrane sodium pump operates, actively pumping sodium out of the cell. In animal cells, the sodium pump is coupled with a potassium pump, which actively absorbs potassium ions from the external environment and transports them into the cell. This combined pump is called the sodium-potassium pump |(Na+, K+)-pump|. Since the pump is present in almost all animal cells and performs a number of important functions in them, it is a good example of an active transport mechanism. Its physiological importance is evidenced by the fact that more than a third of the ATP consumed by an animal cell at rest is spent on pumping sodium and potassium.
Pump is a special carrier protein localized in the membrane in such a way that it penetrates its entire thickness. Sodium and ATP enter it from the inside of the membrane, and potassium from the outside. The transfer of sodium and potassium across the membrane occurs as a result of conformational changes that this protein undergoes. Note that for every two potassium ions absorbed, three sodium ions are removed from the cell. As a result, the contents of the cell become more negative in relation to the external environment, and a potential difference arises between the two sides of the membranes. This limits the entry of negatively charged ions (anions), such as chloride ions, into the cell. It is this circumstance that explains the fact that the concentration of chloride ions in erythrocytes is lower than in blood plasma (Fig. 5.20), although these ions can enter and exit cells due to facilitated diffusion. Positively charged ions (cations), on the contrary, are attracted by the cell. Thus, both factors - concentration and electrical charge - are important in determining in which direction ions will move across the membrane.
Sodium-potassium pump necessary for animal cells to maintain osmotic balance (osmoregulation). If it stops working, the cell will begin to swell and eventually burst. This will happen because with the accumulation of sodium ions, more and more water will enter the cell under the influence of osmotic forces. It is clear that bacteria, fungi and plants with their rigid cell walls do not require such a pump. Animal cells also need it to maintain electrical activity in nerve and muscle cells and, finally, for the active transport of certain substances, such as sugars and amino acids. High concentrations of potassium are also required for protein synthesis, glycolysis, photosynthesis and some other vital processes.
Active transport carried out by all cells, but in some cases it plays a particularly important role. This is exactly the case in the epithelial cells lining the intestines and renal tubules, since the functions of these cells are related to secretion and absorption.
Sodium pump (“Sodium pump”,)
“sodium-potassium pump” (biochemical), a membrane mechanism that maintains a certain ratio of Na + and K + ions in the cell by their active transport against electrochemical and concentration gradients. The cells of most tissues contain more K + ions than Na +, while in the fluid that washes them (blood, lymph, intercellular fluid) the concentration of Na + is significantly higher. A certain number of ions constantly enter and leave cells. Passive cation transport (the movement of ions through the membrane through a system of special channels along electrochemical and concentration gradients) is normally compensated by active ion transport (See Active ion transport). Functioning of "N. n." associated with the transfer of metabolites into cells, and for nerve and muscle fibers also with the mechanism of excitation (See Excitation) (see Membrane theory of excitation). The active transfer of Na + from the cell is associated with K + transport in the opposite direction and is carried out by a special enzyme system - Na, K transport - stimulated by adenosine triphosphatase, localized in the cell membrane. The latter, hydrolyzing adenosine triphosphoric acid (ATP), releases energy, which is spent on the active transfer of cations. Work "N. n." generally depends on the level of cell metabolism. See also Bioelectric potentials,
Permeability of biological membranes.
R. N. Glebov.
Great Soviet Encyclopedia. - M.: Soviet Encyclopedia. 1969-1978 .
See what a “Sodium pump” is in other dictionaries:
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- (French polarisation, first