Types of ion channels. ion channels. Potential independent sodium channels
Last update: 28/10/2013
The second article in the Fundamentals of Human and Animal Physiology series. We will talk about the mechanism of action potential formation - the basis of any movement.
Excitable cells (which are, to one degree or another, all cells of the animal's body) at rest have an excess of negative charge, which forms. If the cell is exposed to external stimulation, it goes into an excited state and generates another potential - the action potential.
This process is implemented by a system of ion channels in the cell membrane, which regulates the concentration of electrically charged particles - ions. All channels, regardless of specialization, are controlled by certain forces. This can be a change in the potential on the cell membrane - in the case of voltage-dependent channels, an increase in the concentration of certain active substances - for ligand-dependent ones, or membrane stretching - for mechanically controlled channels.
Channels are specific proteins embedded in the membrane. Each type of channel allows certain ions to pass through. This is a passive transport system: ions pass through them due to diffusion, and the channels simply control the concentration of passing particles, regulate the membrane permeability for them.
In the formation of the action potential, as well as the resting potential, mainly sodium and potassium ions take part.
Sodium channels have a fairly simple structure: it is a protein of three different subunits that form a pore-like structure - that is, a tube with an internal lumen. The channel can be in three states: closed, open and inactivated (closed and non-excitable). This is ensured by the localization of negative and positive charges in the protein itself; these charges are attracted to the opposite ones existing on the membrane, and thus the channel opens and closes when the state of the membrane changes. When it is open, sodium ions can freely pass through it into the cell along the concentration gradient. This is a very short moment of time - literally fractions of a millisecond.
Potassium channels are even simpler: they are separate subunits that have a trapezoidal shape in the context; they are located almost close to each other, but there is always a gap between them. Potassium channels do not close completely; at rest, potassium freely leaves the cytoplasm (along the concentration gradient).
Both sodium and potassium channels are voltage-dependent - they work depending on changes electrical potential membranes.
During the formation of the action potential, a sharp short-term recharge of the membrane occurs. This is provided by several sequential processes.
First, under the influence of an external stimulus (for example, an electric current), the membrane depolarizes - that is, the charges from its different sides change to opposite ones (inside the cell, the charge turns into positive, outside - into negative). This is a signal for the opening of sodium channels, of which there are a huge number on the surface of one membrane - there can be up to 12 thousand. The moment at which the channels begin to open is called the critical level of depolarization. The current that produces this critical depolarization is called the threshold current.
Interestingly, increasing the current after the threshold has been reached does not change the characteristics of the resulting action potential. What matters for opening the channels is not the amplitude of the current, but the amount of energy received by the membrane - the “amount of electricity”. This pattern is called "all or nothing" - either there is a full-fledged response to irritation with its value from the threshold and above, or there is no answer at all if the irritation has not reached the threshold value. In this case, the value of the threshold value is determined by the duration of the supplied stimulation.
This law is valid, however, only within a single cell. If we take, for example, a nerve composed of a large number of different axons, the amplitude will also matter, because we will see a response to irritation only when the channels are activated in all cells - that is, with a larger total value of the threshold current.
After the opening of the channels, sodium begins to enter the cell, and its current significantly exceeds the current of potassium leaving the gradient. This means that the permeability of the membrane for sodium becomes greater than for potassium. At some point, almost all sodium channels open. This happens like an avalanche: from the point at which the stimulus came, in both directions. Thus, the concentration of sodium in the cell rises sharply.
After that, the ion concentrations should return to the original ones. This provides such a common property of channels as refractoriness: a channel that has worked is inactive for some time after that and cannot be excited under the action of an irritating stimulus.
Sodium channels at the moment of maximum response to irritation become refractory, sodium permeability drops sharply. Potassium channels, on the contrary, begin to work actively, and the current of potassium from the cell increases. Thus, an excess of positively charged ions leaves the cell and the original resting potential is restored. This period of time, until the sodium channels and the initial potential are restored (this can take about a millisecond), the cell is not able to excite.
Since the ability of cells to excite ensures the functioning of the body as a whole and the possibility of central control of all cells of the body, poisons that block channels are among the most dangerous for humans and many animals.
One of the most feared channel blockers is tetrodotoxin, a substance produced by puffer fish. For him, the value of LD50 (50% Level of Death - the dose from which 50 people out of a hundred will die) is 10 milligrams per kilogram of weight, that is, about a thousand times less than for cyanide. Its molecules bind tightly to the sodium channel protein when it is closed and completely block the possibility of an action potential. Some algae produce similar toxins. Scorpion venom, on the contrary, keeps all the channels in a permanently open state.
Well, okay, a scorpion, but why such a terrible weapon for algae is a mystery.
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Properties of ion channels
Selectivity is the selective increased permeability of IR for certain ions. For other ions, the permeability is reduced. Such selectivity is determined by the selective filter - the narrowest point of the channel pore. The filter, in addition to narrow dimensions, can also have a local electric charge. For example, cation-selective channels usually have negatively charged amino acid residues in the protein molecule in the region of their selective filter, which attract positive cations and repel negative anions, preventing them from passing through the pore.
Controlled permeability is the ability of the IC to open or close under certain control actions on the channel. A closed channel has a reduced permeability, and an open channel has an increased one. According to this property, ICs can be classified depending on the methods of their discovery: for example, potential-activated, ligand-activated, etc.
Inactivation is the ability of ICs to automatically lower their permeability some time after their opening, even if the activating factor that opened them continues to operate. Fast inactivation is a special process with its own specific mechanism, different from slow channel closure (slow inactivation). Closing (slow inactivation) of the channel occurs due to processes that are opposite to the processes that ensured its opening, i.e. by changing the conformation of the channel protein. But, for example, in voltage-activated channels, rapid inactivation occurs with the help of a special molecular plug, resembling a plug on a chain, which is usually used in baths. This plug is an amino acid (polypeptide) loop with a thickening at the end in the form of three amino acids, which closes the inner mouth of the channel from the side of the cytoplasm. That is why voltage-dependent ICs for sodium, which ensure the development of an action potential and the movement of a nerve impulse, can let sodium ions into the cell only for a few milliseconds, and then they are automatically closed by their molecular plugs, despite the fact that the depolarization that opens them continues to act. Another mechanism of CI inactivation can be modification of the intracellular mouth of the channel with additional subunits.
Blocking is the ability of IR under the action of blocking substances to fix one of its states and not respond to ordinary control actions. In this state, the channel simply stops responding to control actions. Blocking is caused by blocking substances, which may be called antagonists, blockers, or lytics. Antagonists are substances that prevent the activating action of other substances on the IC. Such substances are able to bind well to the IR receptor site, but are not able to change the state of the channel and cause its response. It turns out the blockade of the receptor and, together with it, the blockade of the IR. It should be remembered that antagonists do not necessarily cause complete blockade of the receptor and its IR, they can act more weakly and only inhibit (oppress) the channel, but not completely stop it. Agonist-antagonists are substances that have a weak stimulating effect on the receptor, but while blocking the action of natural endogenous control substances. Blockers are substances that prevent the operation of an ion channel, for example, the interaction of a mediator with a molecular receptor for it and, therefore, disrupt channel control, blocking it. For example, the action of acetylcholine is blocked by anticholinergics; norepinephrine with adrenaline - blockers; histamine - histamine blockers, etc. Many blockers are used for therapeutic purposes as drugs. Lytics are the same blockers, the term is older and is used as a synonym for a blocker: anticholinergic, adrenolytic, etc.
Plasticity is the ability of an IC to change its properties, its characteristics. The most common mechanism that provides plasticity is the phosphorylation of the amino acids of channel proteins from the inner side of the membrane by protein kinase enzymes. Phosphorus residues from ATP or GTP are attached to channel proteins - and the channel changes its properties. For example, it is fixed in a permanently closed state, or, conversely, in an open state.
12. Ion channels…
The ion channel consists of several subunits, their number in a single ion channel ranges from 3 to 12 subunits. By their organization, the subunits included in the channel can be homologous (of the same type), a number of channels are formed by subunits of different types.
Each of the subunits consists of several (three or more) transmembrane segments (non-polar parts twisted in α-helices), of extra- and intracellular loops and terminal sections of domains (represented by polar regions of molecules that form a domain and protrude beyond the bilipid layer of the membrane) .
Each of the transmembrane segments, extra- and intracellular loops, and terminal sections of domains performs its own function.
Thus, the transmembrane segment 2, organized in the form of an α-helix, determines the selectivity of the channel.
The terminal regions of the domain act as sensors for extra- and intracellular ligands, and one of the transmembrane segments plays the role of a voltage-dependent sensor.
The third transmembrane segments in the subunit are responsible for the operation of the portal channel system, etc.
Ion channels work by the mechanism of facilitated diffusion. When the channels are activated, the movement of ions along them follows a concentration gradient. The speed of movement through the membrane is 10 ions per second.
Specificity of ion channels.
Most of them are selective, i.e. channels that allow only one type of ion to pass through (sodium channels, potassium channels, calcium channels, anion channels).
channel selectivity.
Channel selectivity is determined by the presence of a selective filter.
Its role is played by the initial section of the channel, which has a certain charge, configuration and size (diameter), which allows only a certain type of ions to pass into the channel.
Some of the ion channels are non-selective, such as "leak" channels. These are membrane channels through which, at rest, along the concentration gradient, K + ions leave the cell, however, through these channels, a small amount of Na + ions also enter the cell at rest along the concentration gradient.
Ion channel sensor.
The ion channel sensor is a sensitive part of the channel that perceives signals, the nature of which can be different.
On this basis, there are:
voltage-gated ion channels;
receptor-gated ion channels;
ligand-controlled (ligand-dependent);
mechanically controlled (mechanically dependent).
Channels that have a sensor are called controlled. Some channels do not have a sensor. Such channels are called unmanaged.
The gate system of the ion channel.
The channel has a gate that is closed at rest and opens when a signal is applied. In some channels, two types of gates are distinguished: activation (m-gates) and inactivation (h-gates).
There are three states of ion channels:
a state of rest, when the gate is closed and the channel is inaccessible to ions;
the state of activation, when the gate system is open and ions move through the membrane along the channel;
the state of inactivation, when the channel is closed and does not respond to stimuli.
Conduction speed (conductivity).
There are fast and slow channels. Leak channels are slow, sodium channels in neurons are fast.
In the membrane of any cell there is a large set of various (in terms of speed) ion channels, the activation of which determines the functional state of the cells.
voltage controlled channels.
Potentially controlled channel consists of:
selective filter;
activation and inactivation gates;
voltage sensor.
pores filled with water;
The channel diameter is much larger than the ion diameter; in the selective filter zone, it narrows to atomic sizes, which ensures that this section of the channel performs the function of a selective filter.
The opening and closing of the gate mechanism occurs when the membrane potential changes, and the gate opens at one value of the membrane potential, and closes at a different level of the membrane potential.
It is believed that the change in the electric field of the membrane is perceived by a special section of the channel wall, which is called the voltage sensor.
A change in its state, due to a change in the level of the membrane potential, causes the conformation of the protein molecules that form the channel, and, as a result, leads to the opening or closing of the gate of the ion channel.
Channels (sodium, calcium, potassium) have four homologous domains - subunits (I, II, III, IV). The domain (for example, sodium channels) consists of six transmembrane segments organized in the form of a-helices, each of which plays its own role.
Thus, the transmembrane segment 5 plays the role of a pore, the transmembrane segment 4 is a sensor that responds to changes in the membrane potential, and other transmembrane segments are responsible for the activation and inactivation of the portal channel system. Until the end, the role of individual transmembrane segments and subunits has not been studied.
Sodium channels (internal diameter 0.55 nm) are present in the cells of excitable tissues. Density per 1 µm 2 in different tissues is not the same.
So, in non-myelinated nerve fibers, it is 50-200 channels, and in myelinated nerve fibers (Ranvier intercepts) - 13,000 per 1 micron 2 membrane area. At rest, they are closed. The membrane potential is 70-80 mV.
Exposure to a stimulus changes the membrane potential and activates a voltage-gated sodium channel.
It is activated when the membrane potential shifts from the resting potential level towards the critical level of depolarization.
A strong sodium current provides a shift in the membrane potential to a critical level of depolarization (CDL).
Change in membrane potential up to -50-40 mV, i.e. to the level of a critical level of depolarization, causes the opening of other voltage-dependent Na + channels, through which the incoming sodium current is carried out, which forms the "peak" of the action potential.
Sodium ions move into the cell along the concentration gradient and the chemical gradient through the channel, forming the so-called incoming sodium current, which leads to further rapid development of the depolarization process.
Membrane potential changes sign to the opposite +10-20 mV. A positive membrane potential causes sodium channels to close and become inactivated.
Potential-dependent Na + channels play a leading role in the formation of the action potential, i.e. process of excitation in the cell.
Calcium ions hinder the opening of voltage-gated sodium channels by changing the response parameters.
TO + -channels
Potassium channels (internal diameter 0.30 nm) are present in cytoplasmic membranes, a significant number of channels for potassium "leakage" from the cell were found.
At rest, they are open. Through them, at rest, potassium "leaks" from the cell along the concentration gradient and the electrochemical gradient.
This process is referred to as the outgoing potassium current, which leads to the formation of a membrane resting potential (-70-80 mV). These potassium channels can only be conditionally classified as voltage-dependent.
When the membrane potential changes during depolarization, the potassium current is inactivated.
During repolarization, an incoming K + current is formed through voltage-dependent channels, which is called K + current of delayed rectification.
Another type of voltage-gated K + -channels. A fast outward potassium current arises along them in the subthreshold region of the membrane potential (positive trace potential). Channel inactivation occurs due to trace hyperpolarization.
Another type of voltage-gated potassium channels is activated only after preliminary hyperpolarization, it forms a fast transient potassium current, which is quickly inactivated.
Calcium ions facilitate the opening of voltage-gated potassium channels by changing the response parameters.
Sa + -channels.
Potential-gated channels make a significant contribution both to the regulation of calcium entry into the cytoplasm and to electrogenesis.
Proteins that form calcium channels consist of five subunits (al, a2, b, g, d).
The main subunit al forms the channel itself and contains binding sites for various calcium channel modulators.
Several structurally distinct calcium channel al-subunits have been found in mammalian nerve cells (designated A, B, C, D, and E).
Functionally, different types of calcium channels differ from each other in activation, kinetics, single channel conductance, and pharmacology.
Up to six types of voltage-gated calcium channels have been described in cells (T - , L - , N - , P - , Q - , R - channels).
The activity of voltage-gated plasma membrane channels is regulated by various intracellular second messengers and membrane-bound G-proteins.
Calcium voltage-gated channels are found in large numbers in the cytoplasmic membranes of neurons, myocytes of smooth, striated and cardiac muscles, and in the membranes of the endoplasmic reticulum.
Ca 2+ -channels of the SPR are oligomeric proteins embedded in the SPR membrane.
Sa 2+ - controlled Sa 2+ - SPR channels.
These calcium channels were first isolated from skeletal and cardiac muscles.
It turned out that Ca 2+ -channels of SPR in these muscle tissues have molecular differences and are encoded by different genes.
Ca 2+ -channels of SPR in cardiac muscles are directly connected with high-threshold Ca 2+ -channels of the plasma membrane (L-type) through calcium-binding proteins, thus forming a functionally active structure - a "triad".
In skeletal muscles, plasmalemma depolarization directly activates the release of Ca 2+ from the endoplasmic reticulum due to the fact that the Ca 2+ channels of the plasma membrane serve as voltage-sensitive transmitters of the activating signal directly to the Ca 2+ channels of the SPR through binding proteins.
Thus, Ca 2+ -depots of skeletal muscles have a depolarization-induced Ca 2+ release mechanism (RyRl-type).
Unlike skeletal muscles, endoplasmic Ca 2+ channels of cardiomyocytes are not associated with the plasma membrane, and stimulation of Ca 2+ release from the depot requires an increase in the concentration of cytosolic calcium (RyR2 type).
In addition to these two types of Ca 2+ -activated Ca 2h channels, a third type of Ca 2+ SPR channels (RyR3 type) has recently been identified, which has not yet been sufficiently studied.
All calcium channels are characterized by slow activation and slow inactivation compared to sodium channels.
When the muscle cell is depolarized (protrusions of the cytoplasmic membranes - T-tubules approach the membranes of the endoplasmic reticulum), a voltage-dependent opening of the calcium channels of the membranes of the sarcoplasmic reticulum occurs.
Since, on the one hand, the calcium concentration in the SPR is high (calcium depot), and the calcium concentration in the cytoplasm is low, and, on the other hand, the area of the SPR membrane and the density of calcium channels in it are large, the calcium level in the cytoplasm increases 100 times.
This increase in calcium concentration initiates the process of contraction of myofibrils.
Calcium channels in cardiomyocytes are located in the cytoplasmic membrane and are L-type calcium channels.
They are activated at a membrane potential of +20-40 mV, form an incoming calcium current. They are in an activated state for a long time, form a "plateau" of the cardiomyocyte action potential.
anion channels.
The largest number of channels for chlorine in the cell membrane. There are fewer chloride ions in the cell compared to the intercellular environment. Therefore, when the channels open, chlorine enters the cell along the concentration gradient and the electrochemical gradient.
The number of channels for HCO 3 is not so large, the volume of transport of this anion through the channels is much less.
ion exchangers.
The membrane contains ion exchangers (carrier proteins) that carry out facilitated diffusion of ions, i.e. accelerated coupled movement of ions through the biomembrane along the concentration gradient, such processes are ATP-independent.
The best known are Na + -H +, K + -H +, Ca 2+ -H + exchangers, as well as exchangers that provide the exchange of cations for anionsNa + -HCO- 3, 2CI-Ca 2+ and exchangers that provide the exchange of cation for cation (Na + -Ca 2+) or anion per anion (Cl- HCO3).
Receptor-gated ion channels.
Ligand-gated (ligand-gated) ion channels.
Ligand-gated ion channels are a subspecies of receptor-gated channels and are always combined with a receptor for a biologically active substance (BAS).
The receptors of the considered channels belong to the ionotropic type of membrane receptors, when interacting with biologically active substances (ligands), fast reactions occur.
A ligand-gated ion channel consists of:
pores filled with water;
selective filter;
activation gate;
ligand binding site (receptor). High-energy active BAS has a high
affinity (affinity) for a particular type of receptor. When ion channels are activated, certain ions move along a concentration gradient and an electrochemical gradient.
In a membrane receptor, the ligand binding site may be accessible to the ligand from the outer surface of the membrane.
In this case, hormones and parahormones, ions act as a ligand.
So, when N-cholinergic receptors are activated, sodium channels are activated.
Calcium permeability is initiated by neuronal acetylcholine-gated, glutamate-gated (NMDA and AMPA/kainattypes) receptors and purine receptors.
GABA A receptors are coupled to ionic chloride channels, and glycine receptors are also coupled to chloride channels.
In a membrane receptor, the ligand binding site may be accessible to ligands from the inner surface of the membrane.
In this case, protein kinases activated by second messengers or the second messengers themselves act as ligands.
So, protein kinases A, C, G, by phosphorylation of cation channel proteins, change their permeability.
Mechanically controlled ion channels.
Mechanically controlled ion channels change their conductivity for ions either by changing the tension of the bilipid layer or through the cell cytoskeleton. Many mechanically controlled channels are associated with mechanoreceptors; they exist in auditory cells, muscle spindles, and vascular endothelium.
All mechanically controlled channels are divided into two groups:
stretch-activated cells (SAC);
stretch-inactivated cells (SIC).
Mechanically controlled channels have all the main channel features:
pore filled with water;
gate mechanism;
stretch sensor.
When the channel is activated, ions move along the concentration gradient along it.
Sodium, potassium ATPase.
Sodium, potassium ATPase (sodium-potassium pump, sodium-potassium pump).
Consists of four transmembrane domains: two α-subunits and two β-subunits. The α-subunit is a large domain and the β-subunit is a small one. During ion transport, large subunits are phosphorylated and ions move through them.
Sodium, potassium ATPase plays a crucial role in maintaining sodium and potassium homeostasis in the intra- and extracellular environment:
supports high level K + and low levels of Na + in the cell;
participates in the formation of the resting membrane potential, in the generation of the action potential;
provides Na + conjugated transport of most organic substances through the membrane (secondary active transport);
significantly affects the homeostasis of H 2 O.
Sodium, potassium ATPase, makes the most important contribution to the formation of ionic asymmetry in extra- and intracellular spaces.
The phased work of the sodium, potassium pump provides a non-equivalent exchange of potassium and sodium across the membrane.
Sa + -ATPase (pump).
There are two families of Ca 2+ pumps responsible for the elimination of Ca 2+ ions from the cytoplasm: the Ca 2+ pumps of the plasma membrane and the Ca 2+ pumps of the endoplasmic reticulum.
Although they belong to the same family of proteins (the so-called P-class of ATPases), these pumps show some differences in structure, functional activity and pharmacology.
It is found in large quantities in the cytoplasmic membrane. In the cytoplasm of the cell at rest, the calcium concentration is 10-7 mol/l, and outside the cell it is much more -10-3 mol/l.
Such a significant difference in concentrations is maintained due to the work of the cytoplasmic Ca ++ -ATPase.
The activity of the Ca 2+ -pump of the plasma membrane is directly controlled by Ca 2+ : an increase in the concentration of free calcium in the cytosol activates the Ca 2+ -pump.
At rest, diffusion through calcium ion channels almost does not occur.
Ca-ATPase transports Ca from the cell to the extracellular environment against its concentration gradient. Along the gradient, Ca + enters the cell due to diffusion through ion channels.
The membrane of the endoplasmic reticulum also contains a large amount of Ca ++ -ATPase.
The calcium pump of the endoplasmic reticulum (SERCA) ensures the removal of calcium from the cytosol to the endoplasmic reticulum - "depot" of calcium due to primary active transport.
In the depot, calcium binds to calcium-binding proteins (calsequestrin, calreticulin, etc.).
At least three different isoforms of SERCA pumps have been described so far.
The SERCA1 subtype is exclusively concentrated in fast skeletal muscles, while the SERCA2 pumps are widespread in other tissues. The significance of SERCA3 pumps is less clear.
SERCA2-nacos proteins are divided into two different isoforms: SERCA2a, characteristic of cardiomyocytes and smooth muscles, and SERCA2b, characteristic of brain tissues.
An increase in Ca 2+ in the cytosol activates the uptake of calcium ions into the endoplasmic reticulum, while an increase in free calcium within the endoplasmic reticulum inhibits the SERCA pumps.
H + K + -ATPase (pump).
With the help of this pump (as a result of the hydrolysis of one ATP molecule) in the lining (parietal) cells of the gastric mucosa, two potassium ions are transported from the extracellular space to the cell and two H + ions from the cytosol to the extracellular space during the hydrolysis of one molecule. This mechanism underlies the formation of hydrochloric acid in the stomach.
Ion pump classF.
Mitochondrial ATPase. Catalyzes the final step in ATP synthesis. Mitochondrial crypts contain ATP synthase, which couples oxidation in the Krebs cycle and ADP phosphorylation to ATP.
Ion pump gradeV.
Lysosomal H + -ATPase (lysosomal proton pumps) - proton pumps that provide transport of H + from the cytosol to a number of lysosome organelles, the Golgi apparatus, secretory vesicles. As a result, the pH value decreases, for example, in lysosomes to 5.0, which optimizes the activity of these structures.
Features of ion transport
1. Significant and asymmetric transmembrane! gradient for Na+ and K+ at rest.
Sodium outside the cell (145 mmol/l) is 10 times greater than in the cell (14 mmol/l).
There is about 30 times more potassium in the cell (140 mmol/l) than outside the cell (4 mmol/l).
This feature of the distribution of sodium and potassium ions:
homeostatized by the work of Na + /K + -nacoca;
forms at rest the outgoing potassium current (leakage channel);
generates resting potential;
the work of any potassium channels (voltage-dependent, calcium-dependent, ligand-dependent) is aimed at the formation of the outgoing potassium current.
This either returns the state of the membrane to its original level (activation of voltage-dependent channels in the repolarization phase), or hyperpolarizes the membrane (calcium-dependent, ligand-dependent channels, including those activated by systems of second mediators).
It should be borne in mind that:
the movement of potassium across the membrane is carried out by passive transport;
the formation of excitation (action potential) is always due to the incoming sodium current;
activation of any sodium channels always causes an inward sodium current;
the movement of sodium across the membrane is carried out almost always by passive transport;
in epithelial cells that form a wall of various tubes and cavities in tissues (small intestine, nephron tubules, etc.), in the outer membrane there is always a large number of sodium channels that provide an incoming sodium current when activated, and in the basement membrane - a large number of sodium, potassium pumps that pump sodium out of the cell. Such an asymmetric distribution of these transport systems for sodium ensures its transcellular transport, i.e. from the intestinal lumen, renal tubules into the internal environment of the body;
passive transport of sodium into the cell along the electrochemical gradient leads to the accumulation of energy, which is used for the secondary active transport of many substances.
2. Low level of calcium in the cytosol of the cell.
In the cell at rest, the calcium content (50 nmol/l) is 5000 times lower than outside the cell (2.5 mmol/l).
Such a low level of calcium in the cytosol is not accidental, since calcium in concentrations 10–100 times higher than the initial one acts as a second intracellular mediator in signal realization.
Under such conditions, a rapid increase in calcium in the cytosol is possible due to the activation of calcium channels (facilitated diffusion), which are present in large quantities in the cytoplasmic membrane and in the membrane of the endoplasmic reticulum (endoplasmic reticulum - "depot" of calcium in the cell).
The formation of calcium fluxes, which occurs due to the opening of channels, provides a physiologically significant increase in the calcium concentration in the cytosol.
The low level of calcium in the cytosol of the cell is maintained by Ca 2+ -ATPase, Na + /Ca 2+ -exchangers, calcium-binding proteins of the cytosol.
In addition to the rapid binding of cytosolic Ca 2+ by intracellular Ca 2+ -binding proteins, calcium ions entering the cytosol can be accumulated by the Golgi apparatus or the cell nucleus and captured by mitochondrial Ca 2+ depots.
3. Low level of chlorine in the cell.
In the cell at rest, the content of chlorine (8 mmol/l) is more than 10 times lower than outside the cell (110 mmol/l).
This state is maintained by the operation of the K + /Cl- -transporter.
The change in the functional state of the cell is associated (or caused) with a change in the permeability of the membrane for chlorine. Upon activation of voltage- and ligand-gated chloride channels, the ion enters the cytosol through the channel by passive transport.
In addition, the entry of chlorine into the cytosol is formed by the Na+/K+/2CH-cotransporter and the CG-HCO3 exchanger.
The entry of chlorine into the cell increases the polarity of the membrane up to hyperpolarization.
Features of ion transport play a fundamental role in the formation of bioelectric phenomena in organs and tissues that encode information, determine the functional state of these structures, their transition from one functional state to another.
12. Ion channels…
The ion channel consists of several subunits, their number in a single ion channel ranges from 3 to 12 subunits. By their organization, the subunits included in the channel can be homologous (of the same type), a number of channels are formed by subunits of different types.
Each of the subunits consists of several (three or more) transmembrane segments (non-polar parts twisted in α-helices), of extra- and intracellular loops and terminal sections of domains (represented by polar regions of molecules that form a domain and protrude beyond the bilipid layer of the membrane) .
Each of the transmembrane segments, extra- and intracellular loops, and terminal sections of domains performs its own function.
Thus, the transmembrane segment 2, organized in the form of an α-helix, determines the selectivity of the channel.
The terminal regions of the domain act as sensors for extra- and intracellular ligands, and one of the transmembrane segments plays the role of a voltage-dependent sensor.
The third transmembrane segments in the subunit are responsible for the operation of the portal channel system, etc.
Ion channels work by the mechanism of facilitated diffusion. When the channels are activated, the movement of ions along them follows a concentration gradient. The speed of movement through the membrane is 10 ions per second.
Specificity of ion channels.
Most of them are selective, i.e. channels that allow only one type of ion to pass through (sodium channels, potassium channels, calcium channels, anion channels).
channel selectivity.
Channel selectivity is determined by the presence of a selective filter.
Its role is played by the initial section of the channel, which has a certain charge, configuration and size (diameter), which allows only a certain type of ions to pass into the channel.
Some of the ion channels are non-selective, such as "leak" channels. These are membrane channels through which, at rest, along the concentration gradient, K + ions leave the cell, however, through these channels, a small amount of Na + ions also enter the cell at rest along the concentration gradient.
Ion channel sensor.
The ion channel sensor is a sensitive part of the channel that perceives signals, the nature of which can be different.
On this basis, there are:
voltage-gated ion channels;
receptor-gated ion channels;
ligand-controlled (ligand-dependent);
mechanically controlled (mechanically dependent).
Channels that have a sensor are called controlled. Some channels do not have a sensor. Such channels are called unmanaged.
The gate system of the ion channel.
The channel has a gate that is closed at rest and opens when a signal is applied. In some channels, two types of gates are distinguished: activation (m-gates) and inactivation (h-gates).
There are three states of ion channels:
a state of rest, when the gate is closed and the channel is inaccessible to ions;
the state of activation, when the gate system is open and ions move through the membrane along the channel;
the state of inactivation, when the channel is closed and does not respond to stimuli.
Conduction speed (conductivity).
There are fast and slow channels. Leak channels are slow, sodium channels in neurons are fast.
In the membrane of any cell there is a large set of various (in terms of speed) ion channels, the activation of which determines the functional state of the cells.
voltage controlled channels.
Potentially controlled channel consists of:
selective filter;
activation and inactivation gates;
voltage sensor.
pores filled with water;
The channel diameter is much larger than the ion diameter; in the selective filter zone, it narrows to atomic sizes, which ensures that this section of the channel performs the function of a selective filter.
The opening and closing of the gate mechanism occurs when the membrane potential changes, and the gate opens at one value of the membrane potential, and closes at a different level of the membrane potential.
It is believed that the change in the electric field of the membrane is perceived by a special section of the channel wall, which is called the voltage sensor.
A change in its state, due to a change in the level of the membrane potential, causes the conformation of the protein molecules that form the channel, and, as a result, leads to the opening or closing of the gate of the ion channel.
Channels (sodium, calcium, potassium) have four homologous domains - subunits (I, II, III, IV). The domain (for example, sodium channels) consists of six transmembrane segments organized in the form of a-helices, each of which plays its own role.
Thus, the transmembrane segment 5 plays the role of a pore, the transmembrane segment 4 is a sensor that responds to changes in the membrane potential, and other transmembrane segments are responsible for the activation and inactivation of the portal channel system. Until the end, the role of individual transmembrane segments and subunits has not been studied.
Sodium channels (internal diameter 0.55 nm) are present in the cells of excitable tissues. Density per 1 µm 2 in different tissues is not the same.
So, in non-myelinated nerve fibers, it is 50-200 channels, and in myelinated nerve fibers (Ranvier intercepts) - 13,000 per 1 micron 2 membrane area. At rest, they are closed. The membrane potential is 70-80 mV.
Exposure to a stimulus changes the membrane potential and activates a voltage-gated sodium channel.
It is activated when the membrane potential shifts from the resting potential level towards the critical level of depolarization.
A strong sodium current provides a shift in the membrane potential to a critical level of depolarization (CDL).
Change in membrane potential up to -50-40 mV, i.e. to the level of a critical level of depolarization, causes the opening of other voltage-dependent Na + channels, through which the incoming sodium current is carried out, which forms the "peak" of the action potential.
Sodium ions move into the cell along the concentration gradient and the chemical gradient through the channel, forming the so-called incoming sodium current, which leads to further rapid development of the depolarization process.
Membrane potential changes sign to the opposite +10-20 mV. A positive membrane potential causes sodium channels to close and become inactivated.
Potential-dependent Na + channels play a leading role in the formation of the action potential, i.e. process of excitation in the cell.
Calcium ions hinder the opening of voltage-gated sodium channels by changing the response parameters.
TO + -channels
Potassium channels (internal diameter 0.30 nm) are present in cytoplasmic membranes, a significant number of channels for potassium "leakage" from the cell were found.
At rest, they are open. Through them, at rest, potassium "leaks" from the cell along the concentration gradient and the electrochemical gradient.
This process is referred to as the outgoing potassium current, which leads to the formation of a membrane resting potential (-70-80 mV). These potassium channels can only be conditionally classified as voltage-dependent.
When the membrane potential changes during depolarization, the potassium current is inactivated.
During repolarization, an incoming K + current is formed through voltage-dependent channels, which is called K + current of delayed rectification.
Another type of voltage-gated K + -channels. A fast outward potassium current arises along them in the subthreshold region of the membrane potential (positive trace potential). Channel inactivation occurs due to trace hyperpolarization.
Another type of voltage-gated potassium channels is activated only after preliminary hyperpolarization, it forms a fast transient potassium current, which is quickly inactivated.
Calcium ions facilitate the opening of voltage-gated potassium channels by changing the response parameters.
Sa + -channels.
Potential-gated channels make a significant contribution both to the regulation of calcium entry into the cytoplasm and to electrogenesis.
Proteins that form calcium channels consist of five subunits (al, a2, b, g, d).
The main subunit al forms the channel itself and contains binding sites for various calcium channel modulators.
Several structurally distinct calcium channel al-subunits have been found in mammalian nerve cells (designated A, B, C, D, and E).
Functionally, different types of calcium channels differ from each other in activation, kinetics, single channel conductance, and pharmacology.
Up to six types of voltage-gated calcium channels have been described in cells (T - , L - , N - , P - , Q - , R - channels).
The activity of voltage-gated plasma membrane channels is regulated by various intracellular second messengers and membrane-bound G-proteins.
Calcium voltage-gated channels are found in large numbers in the cytoplasmic membranes of neurons, myocytes of smooth, striated and cardiac muscles, and in the membranes of the endoplasmic reticulum.
Ca 2+ -channels of the SPR are oligomeric proteins embedded in the SPR membrane.
Sa 2+ - controlled Sa 2+ - SPR channels.
These calcium channels were first isolated from skeletal and cardiac muscles.
It turned out that Ca 2+ -channels of SPR in these muscle tissues have molecular differences and are encoded by different genes.
Ca 2+ -channels of SPR in cardiac muscles are directly connected with high-threshold Ca 2+ -channels of the plasma membrane (L-type) through calcium-binding proteins, thus forming a functionally active structure - a "triad".
In skeletal muscles, plasmalemma depolarization directly activates the release of Ca 2+ from the endoplasmic reticulum due to the fact that the Ca 2+ channels of the plasma membrane serve as voltage-sensitive transmitters of the activating signal directly to the Ca 2+ channels of the SPR through binding proteins.
Thus, Ca 2+ -depots of skeletal muscles have a depolarization-induced Ca 2+ release mechanism (RyRl-type).
Unlike skeletal muscles, endoplasmic Ca 2+ channels of cardiomyocytes are not associated with the plasma membrane, and stimulation of Ca 2+ release from the depot requires an increase in the concentration of cytosolic calcium (RyR2 type).
In addition to these two types of Ca 2+ -activated Ca 2h channels, a third type of Ca 2+ SPR channels (RyR3 type) has recently been identified, which has not yet been sufficiently studied.
All calcium channels are characterized by slow activation and slow inactivation compared to sodium channels.
When the muscle cell is depolarized (protrusions of the cytoplasmic membranes - T-tubules approach the membranes of the endoplasmic reticulum), a voltage-dependent opening of the calcium channels of the membranes of the sarcoplasmic reticulum occurs.
Since, on the one hand, the calcium concentration in the SPR is high (calcium depot), and the calcium concentration in the cytoplasm is low, and, on the other hand, the area of the SPR membrane and the density of calcium channels in it are large, the calcium level in the cytoplasm increases 100 times.
This increase in calcium concentration initiates the process of contraction of myofibrils.
Calcium channels in cardiomyocytes are located in the cytoplasmic membrane and are L-type calcium channels.
They are activated at a membrane potential of +20-40 mV, form an incoming calcium current. They are in an activated state for a long time, form a "plateau" of the cardiomyocyte action potential.
anion channels.
The largest number of channels for chlorine in the cell membrane. There are fewer chloride ions in the cell compared to the intercellular environment. Therefore, when the channels open, chlorine enters the cell along the concentration gradient and the electrochemical gradient.
The number of channels for HCO 3 is not so large, the volume of transport of this anion through the channels is much less.
ion exchangers.
The membrane contains ion exchangers (carrier proteins) that carry out facilitated diffusion of ions, i.e. accelerated coupled movement of ions through the biomembrane along the concentration gradient, such processes are ATP-independent.
The best known are Na + -H +, K + -H +, Ca 2+ -H + exchangers, as well as exchangers that provide the exchange of cations for anionsNa + -HCO- 3, 2CI-Ca 2+ and exchangers that provide the exchange of cation for cation (Na + -Ca 2+) or anion per anion (Cl- HCO3).
Receptor-gated ion channels.
Ligand-gated (ligand-gated) ion channels.
Ligand-gated ion channels are a subspecies of receptor-gated channels and are always combined with a receptor for a biologically active substance (BAS).
The receptors of the considered channels belong to the ionotropic type of membrane receptors, when interacting with biologically active substances (ligands), fast reactions occur.
A ligand-gated ion channel consists of:
pores filled with water;
selective filter;
activation gate;
ligand binding site (receptor). High-energy active BAS has a high
affinity (affinity) for a particular type of receptor. When ion channels are activated, certain ions move along a concentration gradient and an electrochemical gradient.
In a membrane receptor, the ligand binding site may be accessible to the ligand from the outer surface of the membrane.
In this case, hormones and parahormones, ions act as a ligand.
So, when N-cholinergic receptors are activated, sodium channels are activated.
Calcium permeability is initiated by neuronal acetylcholine-gated, glutamate-gated (NMDA and AMPA/kainattypes) receptors and purine receptors.
GABA A receptors are coupled to ionic chloride channels, and glycine receptors are also coupled to chloride channels.
In a membrane receptor, the ligand binding site may be accessible to ligands from the inner surface of the membrane.
In this case, protein kinases activated by second messengers or the second messengers themselves act as ligands.
So, protein kinases A, C, G, by phosphorylation of cation channel proteins, change their permeability.
Mechanically controlled ion channels.
Mechanically controlled ion channels change their conductivity for ions either by changing the tension of the bilipid layer or through the cell cytoskeleton. Many mechanically controlled channels are associated with mechanoreceptors; they exist in auditory cells, muscle spindles, and vascular endothelium.
All mechanically controlled channels are divided into two groups:
stretch-activated cells (SAC);
stretch-inactivated cells (SIC).
Mechanically controlled channels have all the main channel features:
pore filled with water;
gate mechanism;
stretch sensor.
When the channel is activated, ions move along the concentration gradient along it.
Sodium, potassium ATPase.
Sodium, potassium ATPase (sodium-potassium pump, sodium-potassium pump).
Consists of four transmembrane domains: two α-subunits and two β-subunits. The α-subunit is a large domain and the β-subunit is a small one. During ion transport, large subunits are phosphorylated and ions move through them.
Sodium, potassium ATPase plays a crucial role in maintaining sodium and potassium homeostasis in the intra- and extracellular environment:
maintains a high level of K + and a low level of Na + in the cell;
participates in the formation of the resting membrane potential, in the generation of the action potential;
provides Na + conjugated transport of most organic substances through the membrane (secondary active transport);
significantly affects the homeostasis of H 2 O.
Sodium, potassium ATPase, makes the most important contribution to the formation of ionic asymmetry in extra- and intracellular spaces.
The phased work of the sodium, potassium pump provides a non-equivalent exchange of potassium and sodium across the membrane.
Sa + -ATPase (pump).
There are two families of Ca 2+ pumps responsible for the elimination of Ca 2+ ions from the cytoplasm: the Ca 2+ pumps of the plasma membrane and the Ca 2+ pumps of the endoplasmic reticulum.
Although they belong to the same family of proteins (the so-called P-class of ATPases), these pumps show some differences in structure, functional activity and pharmacology.
It is found in large quantities in the cytoplasmic membrane. In the cytoplasm of the cell at rest, the calcium concentration is 10-7 mol/l, and outside the cell it is much more -10-3 mol/l.
Such a significant difference in concentrations is maintained due to the work of the cytoplasmic Ca ++ -ATPase.
The activity of the Ca 2+ -pump of the plasma membrane is directly controlled by Ca 2+ : an increase in the concentration of free calcium in the cytosol activates the Ca 2+ -pump.
At rest, diffusion through calcium ion channels almost does not occur.
Ca-ATPase transports Ca from the cell to the extracellular environment against its concentration gradient. Along the gradient, Ca + enters the cell due to diffusion through ion channels.
The membrane of the endoplasmic reticulum also contains a large amount of Ca ++ -ATPase.
The calcium pump of the endoplasmic reticulum (SERCA) ensures the removal of calcium from the cytosol to the endoplasmic reticulum - "depot" of calcium due to primary active transport.
In the depot, calcium binds to calcium-binding proteins (calsequestrin, calreticulin, etc.).
At least three different isoforms of SERCA pumps have been described so far.
The SERCA1 subtype is exclusively concentrated in fast skeletal muscles, while the SERCA2 pumps are widespread in other tissues. The significance of SERCA3 pumps is less clear.
SERCA2-nacos proteins are divided into two different isoforms: SERCA2a, characteristic of cardiomyocytes and smooth muscles, and SERCA2b, characteristic of brain tissues.
An increase in Ca 2+ in the cytosol activates the uptake of calcium ions into the endoplasmic reticulum, while an increase in free calcium within the endoplasmic reticulum inhibits the SERCA pumps.
H + K + -ATPase (pump).
With the help of this pump (as a result of the hydrolysis of one ATP molecule) in the lining (parietal) cells of the gastric mucosa, two potassium ions are transported from the extracellular space to the cell and two H + ions from the cytosol to the extracellular space during the hydrolysis of one molecule. This mechanism underlies the formation of hydrochloric acid in the stomach.
Ion pump classF.
Mitochondrial ATPase. Catalyzes the final step in ATP synthesis. Mitochondrial crypts contain ATP synthase, which couples oxidation in the Krebs cycle and ADP phosphorylation to ATP.
Ion pump gradeV.
Lysosomal H + -ATPase (lysosomal proton pumps) - proton pumps that provide transport of H + from the cytosol to a number of lysosome organelles, the Golgi apparatus, secretory vesicles. As a result, the pH value decreases, for example, in lysosomes to 5.0, which optimizes the activity of these structures.
Features of ion transport
1. Significant and asymmetric transmembrane! gradient for Na+ and K+ at rest.
Sodium outside the cell (145 mmol/l) is 10 times greater than in the cell (14 mmol/l).
There is about 30 times more potassium in the cell (140 mmol/l) than outside the cell (4 mmol/l).
This feature of the distribution of sodium and potassium ions:
homeostatized by the work of Na + /K + -nacoca;
forms at rest the outgoing potassium current (leakage channel);
generates resting potential;
the work of any potassium channels (voltage-dependent, calcium-dependent, ligand-dependent) is aimed at the formation of the outgoing potassium current.
This either returns the state of the membrane to its original level (activation of voltage-dependent channels in the repolarization phase), or hyperpolarizes the membrane (calcium-dependent, ligand-dependent channels, including those activated by systems of second mediators).
It should be borne in mind that:
the movement of potassium across the membrane is carried out by passive transport;
the formation of excitation (action potential) is always due to the incoming sodium current;
activation of any sodium channels always causes an inward sodium current;
the movement of sodium across the membrane is carried out almost always by passive transport;
in epithelial cells that form a wall of various tubes and cavities in tissues (small intestine, nephron tubules, etc.), in the outer membrane there is always a large number of sodium channels that provide an incoming sodium current when activated, and in the basement membrane - a large number of sodium, potassium pumps that pump sodium out of the cell. Such an asymmetric distribution of these transport systems for sodium ensures its transcellular transport, i.e. from the intestinal lumen, renal tubules into the internal environment of the body;
passive transport of sodium into the cell along the electrochemical gradient leads to the accumulation of energy, which is used for the secondary active transport of many substances.
2. Low level of calcium in the cytosol of the cell.
In the cell at rest, the calcium content (50 nmol/l) is 5000 times lower than outside the cell (2.5 mmol/l).
Such a low level of calcium in the cytosol is not accidental, since calcium in concentrations 10–100 times higher than the initial one acts as a second intracellular mediator in signal realization.
Under such conditions, a rapid increase in calcium in the cytosol is possible due to the activation of calcium channels (facilitated diffusion), which are present in large quantities in the cytoplasmic membrane and in the membrane of the endoplasmic reticulum (endoplasmic reticulum - "depot" of calcium in the cell).
The formation of calcium fluxes, which occurs due to the opening of channels, provides a physiologically significant increase in the calcium concentration in the cytosol.
The low level of calcium in the cytosol of the cell is maintained by Ca 2+ -ATPase, Na + /Ca 2+ -exchangers, calcium-binding proteins of the cytosol.
In addition to the rapid binding of cytosolic Ca 2+ by intracellular Ca 2+ -binding proteins, calcium ions entering the cytosol can be accumulated by the Golgi apparatus or the cell nucleus and captured by mitochondrial Ca 2+ depots.
3. Low level of chlorine in the cell.
In the cell at rest, the content of chlorine (8 mmol/l) is more than 10 times lower than outside the cell (110 mmol/l).
This state is maintained by the operation of the K + /Cl- -transporter.
The change in the functional state of the cell is associated (or caused) with a change in the permeability of the membrane for chlorine. Upon activation of voltage- and ligand-gated chloride channels, the ion enters the cytosol through the channel by passive transport.
In addition, the entry of chlorine into the cytosol is formed by the Na+/K+/2CH-cotransporter and the CG-HCO3 exchanger.
The entry of chlorine into the cell increases the polarity of the membrane up to hyperpolarization.
Features of ion transport play a fundamental role in the formation of bioelectric phenomena in organs and tissues that encode information, determine the functional state of these structures, their transition from one functional state to another.
The excitable membrane model according to the Hodgkin-Huxley theory assumes a regulated transport of ions across the membrane. However, the direct transition of the ion through the lipid bilayer is very difficult, and, consequently, the ion flux would also be small.
This and a number of other considerations gave reason to believe that the membrane must contain some special structures - conducting ions. Such structures were found and named ion channels. Similar channels have been isolated from various objects: the plasma membrane of cells, the postsynaptic membrane of muscle cells, and other objects. Ion channels formed by antibiotics are also known.
Main properties of ion channels:
1) selectivity;
2) independence of the operation of individual channels;
3) discrete character of conductivity;
4) dependence of channel parameters on membrane potential.
Let's consider them in order.
1. Selectivity is the ability of ion channels to selectively pass ions of any one type.
Even in the first experiments on the squid axon, it was found that Na+ and Km ions have different effects on the membrane potential. K+ ions change the resting potential, and Na+ ions change the action potential. In the Hodgkin-Huxley model, this is described by introducing independent potassium and sodium ion channels. It was assumed that the former let through only K+ ions, and the latter only Na+ ions.
Measurements have shown that ion channels have absolute selectivity with respect to cations (cation-selective channels) or to anions (anion-selective channels). At the same time, various cations of various chemical elements are able to pass through the cation-selective channels, but the conductivity of the membrane for a minor ion, and hence the current through it, will be significantly lower, for example, for the Na + -channel, the potassium current through it will be 20 times less. The ability of an ion channel to pass various ions is called relative selectivity and is characterized by a selectivity series - the ratio of channel conductivities for different ions taken at the same concentration. In this case, for the main ion, the selectivity is taken as 1. For example, for the Na + channel, this series has the form:
Na + : K + = 1: 0.05.
2. Independence of individual channels. The passage of current through an individual ion channel is independent of whether current flows through other channels. For example, K + channels can be turned on or off, but the current through Na + channels does not change. The influence of channels on each other occurs indirectly: a change in the permeability of any channels (for example, sodium) changes the membrane potential, and it already affects the conductivities of other ion channels.
3. Discrete nature of the conduction of ion channels. Ion channels are a subunit complex of proteins that spans the membrane. In its center there is a tube through which ions can pass. The number of ion channels per 1 μm 2 membrane surface was determined using a radioactively labeled sodium channel blocker - tetrodotoxin. It is known that one TTX molecule binds to only one channel. Then the measurement of the radioactivity of a sample with a known area made it possible to show that there are about 500 sodium channels per 1 μm 2 of the squid axon.
Those transmembrane currents that are measured in conventional experiments, for example, on a squid axon 1 cm long and 1 mm in diameter, that is, with an area of 3 * 10 7 μm 2, are due to a total response (change in conductivity) of 500 3 10 7 -10 10 ion channels. Such a response is characterized by a gradual change in conductivity over time. The response of a single ion channel changes over time in a fundamentally different way: discretely for both Na+ channels, K+-, and Ca 2+ channels.
This was first discovered in 1962 in studies of the conductivity of lipid bilayer membranes (BLMs) when microquantities of some substance that induced excitation were added to the solution surrounding the membrane. A constant voltage was applied to the BLM and the current I(t) was recorded. Recording the current in time had the form of jumps between two conducting states.
One of effective methods An experimental study of ion channels was the method of local fixing of the membrane potential ("Patch Clamp") developed in the 1980s (Fig. 10).
Rice. 10. Method of local fixation of the membrane potential. ME - microelectrode, IR - ion channel, M - cell membrane, SFP - potential clamp circuit, I - single channel current
The essence of the method lies in the fact that the ME microelectrode (Fig. 10) with a thin end having a diameter of 0.5–1 μm is sucked to the membrane in such a way that an ion channel enters its inner diameter. Then, using the potential-clamping circuit, it is possible to measure currents that pass only through a single channel of the membrane, and not through all channels simultaneously, as happens when using standard method fixing potential.
The results of experiments performed on various ion channels showed that the conductivity of the ion channel is discrete and it can be in two states: open or closed. Transitions between states occur at random times and obey statistical patterns. It cannot be said that this ion channel will open exactly at this moment in time. One can only make a statement about the probability of opening a channel in a certain time interval.
4. Dependence of the channel parameters on the membrane potential. The ion channels of nerve fibers are sensitive to the membrane potential, for example, the sodium and potassium channels of the squid axon. This is manifested in the fact that after the beginning of membrane depolarization, the corresponding currents begin to change with one or another kinetics. This process occurs as follows: The ion-selective channel has a sensor - some element of its design, sensitive to the action of an electric field (Fig. 11). When the membrane potential changes, the magnitude of the force acting on it changes, as a result, this part of the ion channel moves and changes the probability of opening or closing the gate - a kind of damper acting according to the all-or-nothing law. It has been experimentally shown that under the action of membrane depolarization, the probability of the transition of the sodium channel to the conducting state increases. The voltage jump on the membrane, created during measurements by the method of clamping the potential, leads to the fact that a large number of channels open. More charges pass through them, which means, on average, more current flows. It is essential that the growth process of the channel conductivity is determined by the increase in the probability of the channel transition to the open state, and not by the increase in the diameter of the open channel. This is the modern idea of the mechanism of current passage through a single channel.
Smooth kinetic curves of currents recorded during electrical measurements on large membranes are obtained due to the summation of many jump currents flowing through individual channels. Their summation, as shown above, sharply reduces the fluctuations and gives rather smooth time dependences of the transmembrane current.
Ion channels can be sensitive to other physical impact: mechanical deformation, chemical bonding, etc. In this case, they are the structural basis, respectively, of mechanoreceptors, chemoreceptors, etc.
The study of ion channels in membranes is one of the important tasks of modern biophysics.
Structure of the ion channel.
The ion-selective channel consists of the following parts (Fig. 11): a protein part immersed in the bilayer, which has a subunit structure; a selective filter formed by negatively charged oxygen atoms, which are rigidly located at a certain distance from each other and pass ions of only a certain diameter; gate part.
The gates of the ion channel are controlled by the membrane potential and can be either in the closed state (dashed line) or in the open state (solid line). The normal position of the sodium channel gate is closed. Under the action of an electric field, the probability of an open state increases, the gate opens and the flow of hydrated ions gets the opportunity to pass through the selective filter.
If the ion fits in diameter, then it sheds the hydration shell and jumps to the other side of the ion channel. If the ion is too large in diameter, such as tetraethylammonium, it is unable to pass through the filter and cannot cross the membrane. If, on the contrary, the ion is too small, then it has difficulties in the selective filter, this time associated with the difficulty of discarding the hydration shell of the ion.
Ion channel blockers either cannot pass through it, getting stuck in the filter, or, if they are large molecules, like TTX, they sterically match any entrance to the channel. Since blockers carry a positive charge, their charged part is drawn into the channel to the selective filter as an ordinary cation, and the macromolecule clogs it.
Thus, changes in the electrical properties of excitable biomembranes are carried out using ion channels. These are protein macromolecules penetrating the lipid bilayer, which can be in several discrete states. The properties of channels selective for K + , Na + and Ca 2+ ions can depend differently on the membrane potential, which determines the dynamics of the action potential in the membrane, as well as differences in such potentials in the membranes of different cells.
Rice. 11. Scheme of the structure of the sodium ion channel of the membrane in the context
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