Channels of cell membranes. Structure and functions of the membrane, ion channels and their functions, ion gradients
12. Ion channels...
An ion channel consists of several subunits; their number in an individual ion channel ranges from 3 to 12 subunits. In terms of 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 into α-helices), extra- and intracellular loops and terminal sections of domains (represented by the polar regions of the molecules that form the 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, transmembrane segment 2, organized in the form of an α-helix, determines the selectivity of the channel.
The terminal sections 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 gating channel system, etc.
Ion channels operate by the mechanism of facilitated diffusion. The movement of ions through them when the channels are activated follows a concentration gradient. The rate 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.
The selectivity of the channel 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 K + ions leave the cell at rest along a concentration gradient, but through these channels a small amount of Na + ions also enters the cell at rest along a concentration gradient.
Ion channel sensor.
The ion channel sensor is the sensitive part of the channel that perceives signals, the nature of which can be different.
On this basis, the following are distinguished:
voltage-gated ion channels;
receptor-gated ion channels;
ligand-gated (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 uncontrollable.
Ion channel gate system.
The channel has a gate that is closed when at rest and opens when exposed to a signal. Some channels have two types of gates: activation (m-gate) and inactivation (h-gate).
There are three states of ion channels:
a state of rest when the gate is closed and the channel is inaccessible to ions;
activation state when the gate system is open and ions move through the membrane along the channel;
a state of inactivation when the channel is closed and does not respond to stimuli.
Conduction speed (conduction).
There are fast and slow channels. “Leak” channels are slow, sodium channels in neurons are fast.
The membrane of any cell contains 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.
The voltage-controlled channel consists of:
selective filter;
activation and inactivation gates;
voltage sensor.
pores filled with water;
The diameter of the channel is significantly larger than the diameter of the ion; in the selective filter zone it narrows to atomic sizes, this 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, with the gate opening at one value of the membrane potential and closing at a different level of membrane potential.
It is believed that changes in the electric field of the membrane are sensed by a special section of the channel wall, which is called a voltage sensor.
A change in its state, caused by a change in the level of membrane potential, causes the conformation of the protein molecules that form the channel and, as a consequence, 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 (using the example of sodium channels) consists of six transmembrane segments organized in the form of α-helices, each of which plays a different role.
Thus, transmembrane segment 5 plays the role of a pore, transmembrane segment 4 is a sensor that responds to changes in membrane potential, other transmembrane segments are responsible for the activation and inactivation of the channel’s gate system. The role of individual transmembrane segments and subunits is not fully understood.
Sodium channels (internal diameter 0.55 nm) are present in cells of excitable tissues. The density per 1 micron 2 is not the same in different tissues.
Thus, in non-myelinated nerve fibers it is 50-200 channels, and in myelinated nerve fibers (nodes of Ranvier) - 13,000 per 1 µm 2 membrane area. At rest they are closed. The membrane potential is 70-80 mV.
Exposure to the stimulus changes the membrane potential and activates the 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 shifts the membrane potential to a critical depolarization level (CDL).
Changing the membrane potential to -50-40 mV, i.e. to the level of a critical level of depolarization, causes the opening of other voltage-gated Na + channels, through which the incoming sodium current is carried out, forming the “peak” of the action potential.
Sodium ions along the concentration gradient and chemical gradient along the channel move into the cell, forming the so-called incoming sodium current, which leads to further rapid development of the depolarization process.
The membrane potential changes sign to the opposite +10-20 mV. A positive membrane potential causes the closure of sodium channels, their inactivation.
Voltage-gated No+ channels play a leading role in the formation of the action potential, i.e. process of excitation in the cell.
Calcium ions impede the opening of voltage-gated sodium channels, changing response parameters.
TO + -channels
Potassium channels (internal diameter 0.30 nm) are present in cytoplasmic membranes; a significant number of potassium “leak” channels from the cell have been detected.
At rest they are open. Through them, in a state of rest, potassium “leaks” from the cell along a concentration gradient and an electrochemical gradient.
This process is referred to as an outgoing potassium current, which leads to the formation of a resting membrane potential (-70-80 mV). These potassium channels can only be conditionally classified as voltage-gated.
When the membrane potential changes during depolarization, the potassium current is inactivated.
During repolarization, an incoming K + current is formed through voltage-gated channels, which is called the K + delayed rectification current.
Another type of voltage-gated K + channels. A fast outgoing potassium current appears along them in the subthreshold region of the membrane potential (positive trace potential). Inactivation of the channel 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 that is quickly inactivated.
Calcium ions facilitate the opening of voltage-gated potassium channels, changing response parameters.
Ca + -channels.
Voltage-gated channels make a significant contribution to both the regulation of calcium entry into the cytoplasm and electrogenesis.
The 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 α-calcium channel subunits have been discovered 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 plasma membrane voltage-gated channels is regulated by various intracellular second messengers and membrane-bound G proteins.
Voltage-gated calcium channels are found in large quantities in the cytoplasmic membranes of neurons, myocytes of smooth, striated and cardiac muscles and in the membranes of the endoplasmic reticulum.
The SPR Ca 2+ channels are oligomeric proteins embedded in the SPR membrane.
Ca 2+ - controlled by Sa 2+ - SPR channels.
These calcium channels were first isolated from skeletal and cardiac muscle.
It turned out that the SPR Ca 2+ channels in these muscle tissues have molecular differences and are encoded by different genes.
Ca 2+ channels of the SPR in cardiac muscles are directly connected to high-threshold Ca 2+ channels of the plasmalemma (L-type) through calcium-binding proteins, thus forming a functionally active structure - a “triad”.
In skeletal muscle, depolarization of the plasma membrane 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+ stores in skeletal muscles have a mechanism for Ca 2+ release caused by depolarization (RyRl type).
Unlike skeletal muscles, endoplasmic Ca 2+ channels of cardiomyocytes are not connected to the plasmalemma, and to stimulate the release of Ca 2+ from the store, an increase in the concentration of cytosolic calcium (RyR2 type) is required.
In addition to these two types of Ca 2+ -activated Ca 2h channels, a third type of Ca 2+ channels SPR (RyR3 type) has recently been identified, which has not yet been sufficiently studied.
All calcium channels exhibit slow activation and slow inactivation compared to sodium channels.
When a muscle cell depolarizes (protrusions of cytoplasmic membranes - T-tubules approach the membranes of the endoplasmic reticulum), a voltage-dependent opening of 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 level of calcium in the cytoplasm increases 100 times.
This increase in calcium concentration initiates the process of myofibril contraction.
Calcium channels in cardiomyocytes are located in the cytoplasm plasma membrane and belong to L-type calcium channels.
They are activated at a membrane potential of +20-40 mV, forming an incoming calcium current. They remain in an activated state for a long time, forming a “plateau” of the action potential of the cardiomyocyte.
Anion channels.
The largest number of chlorine channels in the cell membrane. There are fewer chlorine ions in the cell compared to the intercellular environment. Therefore, when the channels open, chlorine enters the cell along a concentration gradient and an electrochemical gradient.
The number of channels for HCO 3 is not so large; the volume of transport of this anion through the channels is significantly less.
Ion exchangers.
The membrane contains ion exchangers (transport proteins), which facilitate facilitated diffusion of ions, i.e. accelerated coupled movement of ions through the biomembrane along a 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 to anion (Cl- HCO3).
Receptor-gated ion channels.
Ligand-gated (ligand-dependent) ion channels.
Ligand-gated ion channels are a subtype of receptor-gated channels and are always combined with a receptor for a biologically active substance (BAS).
The receptors of the channels under consideration belong to the ionotropic type of membrane receptors, the interaction of which with biologically active substances (ligands) results in rapid reactions.
A ligand-gated ion channel consists of:
pores filled with water;
selective filter;
activation gate;
ligand binding site (receptor). A highly energetically active biologically active substance has a high
affinity (affinity) for a certain 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 and ions act as ligands.
Thus, when N-cholinergic receptors are activated, sodium channels are activated.
Calcium permeability is initiated by neuronal acetylcholine-gated, glutamate-gated (NMDA and AMPA/kainate-type) receptors and purine receptors.
GABA A receptors are coupled to chloride ion 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.
Thus, protein kinases A, C, G, phosphorylating cation channel proteins, change their permeability.
Mechanically controlled ion channels.
Mechanically gated ion channels change their conductance to ions either by changing the tension of the lipid bilayer 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 characteristics:
time filled with water;
gate mechanism;
stretch sensor.
When a channel is activated, ions move along a concentration gradient.
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 the large domain, and the β subunit is the small domain. During ion transport, large subunits are phosphorylated and ions move through them.
Sodium, potassium ATPase plays a critical 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 and the generation of action potentials;
provides Na + coupled transport of most organic substances across the membrane (secondary active transport);
significantly affects H2O homeostasis.
Sodium, a potassium ATPase, makes the most important contribution to the formation of ionic asymmetry in extra- and intracellular spaces.
The gradual operation of the sodium and potassium pump ensures an unequal exchange of potassium and sodium across the membrane.
Ca + -ATPase (pump).
There are two families of Ca 2+ pumps responsible for the removal of Ca 2+ ions from the cytoplasm: Ca 2+ pumps of the plasmalemma and Ca 2+ pumps of the endoplasmic reticulum.
Although they belong to the same family of proteins (the so-called P-class ATPases), these pumps show some differences in structure, functional activity and pharmacology.
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 higher - 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 plasma membrane Ca 2+ pump is controlled directly by Ca 2+: an increase in the concentration of free calcium in the cytosol activates the Ca 2+ pump.
At rest, there is almost no diffusion through calcium ion channels.
Ca-ATPase transports Ca from the cell to the extracellular environment against its concentration gradient. Along a 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 endoplasmic reticulum calcium pump (SERCA) ensures the removal of calcium from the cytosol into the endoplasmic reticulum - a calcium “depot” 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 now been described.
SERCA1 subtypes are concentrated exclusively in fast skeletal muscles; SERCA2 pumps are widely distributed in other tissues. The significance of SERCA3 pumps is less clear.
SERCA2 proteins are divided into two different isoforms: SERCA2a, characteristic of cardiomyocytes and smooth muscles, and SERCA2b, characteristic of brain tissue.
An increase in cytosolic Ca 2+ activates the uptake of calcium ions into the endoplasmic reticulum, while an increase in free calcium within the endoplasmic reticulum inhibits SERCA pumps.
H+ K+ -ATPase (pump).
With the help of this pump (as a result of the hydrolysis of one ATP molecule), two potassium ions are transported from the extracellular space into the cell and two H+ ions from the cytosol into the extracellular space during the hydrolysis of one molecule in the parietal cells of the gastric mucosa. This mechanism underlies the formation of hydrochloric acid in the stomach.
Ion pump classF.
Mitochondrial ATPase. Catalyzes the final stage of ATP synthesis. Mitochondrial crypts contain ATP synthase, which couples oxidation in the Krebs cycle and phosphorylation of ADP to ATP.
Ion pump classV.
Lysosomal H + -ATPases (lysosomal proton pumps) - proton pumps that provide transport of H + from the cytosol to a number of organelles - lysosomes, 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 asymmetrical transmembrane! gradient for Na + and K + at rest.
Sodium outside the cell (145 mmol/l) is 10 times more than in the cell (14 mmol/l).
There is approximately 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:
homeostatic by the work of Na + /K + -nacoca;
forms an outgoing potassium current at rest (leakage channel);
forms resting potential;
the work of any potassium channels (voltage-dependent, calcium-dependent, ligand-dependent) is aimed at the formation of an outgoing potassium current.
This either returns the state of the membrane to its original level (activation of voltage-dependent channels during the repolarization phase), or hyperpolarizes the membrane (calcium-dependent, ligand-dependent channels, including those activated by second messenger systems).
Please keep 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 channel always causes an inward sodium current;
the movement of sodium across the membrane is almost always carried out by passive transport;
in epithelial cells that form the walls 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, which, upon activation, provide an incoming sodium current, and in the basement membrane - a large number of sodium, potassium pumps that pump sodium out of the cell. This asymmetrical distribution of these transport systems for sodium it 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 an electrochemical gradient leads to the accumulation of energy, which is used for 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 messenger in the implementation of the signal.
In such conditions it is possible rapid increase calcium in the cytosol 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 is the “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 concentration of calcium in the cytosol.
Low level calcium in the cytosol of the cell is maintained by Ca 2+ -ATPase, Na + /Ca 2+ -exchangers, and 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+ stores.
3. Low chlorine levels in the cage.
In the cell at rest, the chlorine content (8 mmol/l) is more than 10 times lower than outside the cell (110 mmol/l).
This state is maintained by the work 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 to chlorine. When voltage- and ligand-gated chloride channels are activated, the ion enters the cytosol through the channel by passive transport.
In addition, the entry of chlorine into the cytosol is formed due to the Na + /K + /2CH cotransporter and the CH-HCO 3 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 bioelectrical phenomena in organs and tissues that encode information and determine the functional state of these structures and their transition from one functional state to another.
According to modern concepts, biological membranes form the outer shell of all living cells. One of the main structural features is that membranes always form closed spaces. This fact helps them perform the most important functions:
Barrier (creation of concentration gradients, which prevents the free diffusion of substances). This ensures the creation of a resting potential and the generation of an action potential.
Regulatory (fine regulation of intracellular contents and intracellular reactions due to the reception of biologically active substances, which leads to changes in the activity of membrane enzymatic systems and the launch of mechanisms of secondary messengers (intermediaries).
Conversion of stimulus energy into electrical signals (in receptors).
Release of neurotransmitters in synoptic endings.
Chemical analysis showed that the membranes mainly consist of lipids and proteins, the amount of which varies depending on different types cells. Currently, the fluid mosaic model of the cell membrane is the most recognized.
According to this model, the membrane is represented by a bilayer of phospholipid molecules. In this case, the hydrophobic ends of the molecules are located inside the bilayer, and the hydrophilic ends are directed into the aqueous phase, which contributes to the formation of a separation between two phases: extra- and intracellular. Globular proteins are integrated into the phospholipid bilayer, the polar regions of which form a hydrophilic surface in the aqueous phase. These integrated proteins perform various functions:
receptor,
enzymatic,
form ion channels
are diaphragm pumps,
transport ions and molecules.
General understanding of the structure and function of ion channels.
Ion channels are special formations in the cell membrane, which are oligomeric (consisting of several subunits) proteins. The central formation of the channel is a protein molecule that penetrates the membrane in such a way that a channel-pore is formed in its hydrophilic center, through which compounds whose diameter does not exceed the diameter of the pore (usually ions) can penetrate into the cell.
Around the main subunit of the channel there is a system of several subunits that form sites for interaction with membrane regulatory proteins, various mediators, and pharmacologically active substances.
Classification of ion channels according to their functions:
1) according to the number of ions for which the channel is permeable, channels are divided into selective (permeable to only one type of ion) and non-selective (permeable to several types of ions);
2) by the nature of the ions that they pass through the Na +, Ca ++, Cl -, K + channels;
3) according to the method of regulation, they are divided into voltage-dependent and voltage-independent. Voltage-gated channels respond to changes in cell membrane potential, and when the potential reaches a certain value, the channel enters an active state, beginning to pass ions along their concentration gradient. Thus, sodium and fast calcium channels are voltage-dependent, their activation occurs when the membrane potential decreases to -50-60 mV, while the current of Na + and Ca ++ ions into the cell causes a drop in the resting potential and the generation of AP. Voltage-gated potassium channels are activated during the development of AP and, providing a flow of K + ions from the cell, cause membrane repolarization.
Voltage-independent channels do not respond to changes in membrane potential, but to the interaction of the receptors with which they are interconnected and their ligands. Thus, Cl - channels are associated with g-aminobutyric acid receptors and when these receptors interact with it, they are activated and provide a flow of chlorine ions into the cell, causing its hyperpolarization and decreased excitability.
3. Resting membrane potential and its origin.
The term "membrane potential peace » It is customary to call the transmembrane potential difference that exists between the cytoplasm and the external solution surrounding the cell. When a cell (fiber) is in a state of physiological rest, its internal charge is negative in relation to the external one, which is conventionally taken as zero. In different tissues, the membrane potential is characterized by different values: the largest in muscle tissue is -80-90 mV, in nervous tissue -70 mV, in connective tissue -35-40 mV, in epithelial tissue -20 mV.
The formation of MPP depends on the concentration of K +, Na +, Ca 2+, Cl - ions, and on the structural features of the cell membrane. In particular, ion channels present in the membrane have the following properties:
1. Selectivity (selective permeability)
2. Electrical excitability.
At rest, sodium channels are all closed, while most potassium channels are open. Channels can open and close. In the membrane there are leakage channels(nonspecific), which are permeable to all elements, but more permeable to potassium. Potassium channels are always open, and ions move through these channels along a concentration and electrochemical gradient.
According to the membrane-ion theory, the presence of MPP is due to:
continuous movement of ions through the ion channels of the membrane,
a constantly existing difference in cation concentrations on both sides of the membrane,
continuous operation of the sodium-potassium pump.
different permeability of channels for these ions.
There are a lot of K+ ions in the cell, but little outside, Na+ - on the contrary, a lot outside the cell and little in the cell. There are slightly more Cl ions outside the cell than inside. There are many organic anions inside the cell, which mainly provide a negative charge on the inner surface of the membrane.
At rest, the cell membrane is permeable only to K + ions. Potassium ions at rest are constantly released into the environment, where there is a high concentration of Na +. Therefore, at rest, the outer surface of the membrane is positively charged. High-molecular organic anions (proteins) are concentrated at the inner surface of the membrane and determine its negative charge. They electrostatically retain K+ ions on the other side of the membrane. The main role in the formation of MPP belongs to K ions + .
Despite the flow of ions through the leakage channels, the difference in ion concentration is not equalized, i.e. always remains constant. This does not happen because Na + - K + - pumps exist in membranes. They continuously pump Na+ out of the cell and introduce K+ into the cytoplasm against the concentration gradient. For 3 Na + ions that are removed from the cell, 2 K + ions are introduced inside. The transfer of ions against the concentration gradient is carried out by active transport (with energy consumption). In the absence of ATP energy, the cell dies.
The presence of a resting potential allows a cell to move from a state of functional rest to a state of excitation almost instantly after the action of a stimulus.
When excited, the value of the initial resting potential decreases with membrane recharging. When the internal charge of the membrane becomes less negative, the membrane depolarizes and an action potential begins to develop.
4. Action potential and mechanism of its origin.
The relationship between the phases of excitability and the phases of the action potential.
Action potential called a rapid oscillation of membrane potential that occurs when nerve, muscle and secretory cells are excited. It is based on changes in the ionic permeability of the membrane. The amplitude and nature of changes in the action potential depend little on the strength of the stimulus that causes it; it is only important that this strength is not less than a certain critical value, which is called the threshold of irritation.
Threshold of irritation- this is the minimum force at which a minimum response occurs. To characterize the threshold of irritation, the concept is used rheobase(reo – current, base – main).
In addition to threshold ones, there are subthreshold stimuli, which cannot cause a response, but cause a shift in metabolism in the cell. There are also suprathreshold stimuli.
Having arisen, the PD spreads along the membrane, without changing its amplitude. It distinguishes phases:
Depolarization:
a) slow depolarization;
b) rapid depolarization.
Repolarization:
a) rapid repolarization;
b) slow repolarization (negative trace potential)
Hyperpolarization (positive trace potential)
12. Ion channels...
An ion channel consists of several subunits; their number in an individual ion channel ranges from 3 to 12 subunits. In terms of 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 into α-helices), extra- and intracellular loops and terminal sections of domains (represented by the polar regions of the molecules that form the 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, transmembrane segment 2, organized in the form of an α-helix, determines the selectivity of the channel.
The terminal sections 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 gating channel system, etc.
Ion channels operate by the mechanism of facilitated diffusion. The movement of ions through them when the channels are activated follows a concentration gradient. The rate 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.
The selectivity of the channel 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 K + ions leave the cell at rest along a concentration gradient, but through these channels a small amount of Na + ions also enters the cell at rest along a concentration gradient.
Ion channel sensor.
The ion channel sensor is the sensitive part of the channel that perceives signals, the nature of which can be different.
On this basis, the following are distinguished:
voltage-gated ion channels;
receptor-gated ion channels;
ligand-gated (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 uncontrollable.
Ion channel gate system.
The channel has a gate that is closed when at rest and opens when exposed to a signal. Some channels have two types of gates: activation (m-gate) and inactivation (h-gate).
There are three states of ion channels:
a state of rest when the gate is closed and the channel is inaccessible to ions;
activation state when the gate system is open and ions move through the membrane along the channel;
a state of inactivation when the channel is closed and does not respond to stimuli.
Conduction speed (conduction).
There are fast and slow channels. “Leak” channels are slow, sodium channels in neurons are fast.
The membrane of any cell contains 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.
The voltage-controlled channel consists of:
selective filter;
activation and inactivation gates;
voltage sensor.
pores filled with water;
The diameter of the channel is significantly larger than the diameter of the ion; in the selective filter zone it narrows to atomic sizes, this 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, with the gate opening at one value of the membrane potential and closing at a different level of membrane potential.
It is believed that changes in the electric field of the membrane are sensed by a special section of the channel wall, which is called a voltage sensor.
A change in its state, caused by a change in the level of membrane potential, causes the conformation of the protein molecules that form the channel and, as a consequence, 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 (using the example of sodium channels) consists of six transmembrane segments organized in the form of α-helices, each of which plays a different role.
Thus, transmembrane segment 5 plays the role of a pore, transmembrane segment 4 is a sensor that responds to changes in membrane potential, other transmembrane segments are responsible for the activation and inactivation of the channel’s gate system. The role of individual transmembrane segments and subunits is not fully understood.
Sodium channels (internal diameter 0.55 nm) are present in cells of excitable tissues. The density per 1 micron 2 is not the same in different tissues.
Thus, in non-myelinated nerve fibers it is 50-200 channels, and in myelinated nerve fibers (nodes of Ranvier) - 13,000 per 1 µm 2 membrane area. At rest they are closed. The membrane potential is 70-80 mV.
Exposure to the stimulus changes the membrane potential and activates the 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 shifts the membrane potential to a critical depolarization level (CDL).
Changing the membrane potential to -50-40 mV, i.e. to the level of a critical level of depolarization, causes the opening of other voltage-gated Na + channels, through which the incoming sodium current is carried out, forming the “peak” of the action potential.
Sodium ions along the concentration gradient and chemical gradient along the channel move into the cell, forming the so-called incoming sodium current, which leads to further rapid development of the depolarization process.
The membrane potential changes sign to the opposite +10-20 mV. A positive membrane potential causes the closure of sodium channels, their inactivation.
Voltage-gated No+ channels play a leading role in the formation of the action potential, i.e. process of excitation in the cell.
Calcium ions impede the opening of voltage-gated sodium channels, changing response parameters.
TO + -channels
Potassium channels (internal diameter 0.30 nm) are present in cytoplasmic membranes; a significant number of potassium “leak” channels from the cell have been detected.
At rest they are open. Through them, in a state of rest, potassium “leaks” from the cell along a concentration gradient and an electrochemical gradient.
This process is referred to as an outgoing potassium current, which leads to the formation of a resting membrane potential (-70-80 mV). These potassium channels can only be conditionally classified as voltage-gated.
When the membrane potential changes during depolarization, the potassium current is inactivated.
During repolarization, an incoming K + current is formed through voltage-gated channels, which is called the K + delayed rectification current.
Another type of voltage-gated K + channels. A fast outgoing potassium current appears along them in the subthreshold region of the membrane potential (positive trace potential). Inactivation of the channel 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 that is quickly inactivated.
Calcium ions facilitate the opening of voltage-gated potassium channels, changing response parameters.
Ca + -channels.
Voltage-gated channels make a significant contribution to both the regulation of calcium entry into the cytoplasm and electrogenesis.
The 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 α-calcium channel subunits have been discovered 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 plasma membrane voltage-gated channels is regulated by various intracellular second messengers and membrane-bound G proteins.
Voltage-gated calcium channels are found in large quantities in the cytoplasmic membranes of neurons, myocytes of smooth, striated and cardiac muscles, and in the membranes of the endoplasmic reticulum.
The SPR Ca 2+ channels are oligomeric proteins embedded in the SPR membrane.
Ca 2+ - controlled by Sa 2+ - SPR channels.
These calcium channels were first isolated from skeletal and cardiac muscle.
It turned out that the SPR Ca 2+ channels in these muscle tissues have molecular differences and are encoded by different genes.
Ca 2+ channels of the SPR in cardiac muscles are directly connected to high-threshold Ca 2+ channels of the plasmalemma (L-type) through calcium-binding proteins, thus forming a functionally active structure - a “triad”.
In skeletal muscle, depolarization of the plasma membrane 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+ stores in skeletal muscles have a mechanism for Ca 2+ release caused by depolarization (RyRl type).
Unlike skeletal muscles, endoplasmic Ca 2+ channels of cardiomyocytes are not connected to the plasmalemma, and to stimulate the release of Ca 2+ from the store, an increase in the concentration of cytosolic calcium (RyR2 type) is required.
In addition to these two types of Ca 2+ -activated Ca 2h channels, a third type of Ca 2+ channels SPR (RyR3 type) has recently been identified, which has not yet been sufficiently studied.
All calcium channels exhibit slow activation and slow inactivation compared to sodium channels.
When a muscle cell depolarizes (protrusions of cytoplasmic membranes - T-tubules approach the membranes of the endoplasmic reticulum), a voltage-dependent opening of 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 level of calcium in the cytoplasm increases 100 times.
This increase in calcium concentration initiates the process of myofibril contraction.
Calcium channels in cardiomyocytes are located in the cytoplasmic membrane and belong to L-type calcium channels.
They are activated at a membrane potential of +20-40 mV, forming an incoming calcium current. They remain in an activated state for a long time, forming a “plateau” of the action potential of the cardiomyocyte.
Anion channels.
The largest number of chlorine channels in the cell membrane. There are fewer chlorine ions in the cell compared to the intercellular environment. Therefore, when the channels open, chlorine enters the cell along a concentration gradient and an electrochemical gradient.
The number of channels for HCO 3 is not so large; the volume of transport of this anion through the channels is significantly less.
Ion exchangers.
The membrane contains ion exchangers (transport proteins), which facilitate facilitated diffusion of ions, i.e. accelerated coupled movement of ions through the biomembrane along a 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 to anion (Cl- HCO3).
Receptor-gated ion channels.
Ligand-gated (ligand-dependent) ion channels.
Ligand-gated ion channels are a subtype of receptor-gated channels and are always combined with a receptor for a biologically active substance (BAS).
The receptors of the channels under consideration belong to the ionotropic type of membrane receptors, the interaction of which with biologically active substances (ligands) results in rapid reactions.
A ligand-gated ion channel consists of:
pores filled with water;
selective filter;
activation gate;
ligand binding site (receptor). A highly energetically active biologically active substance has a high
affinity (affinity) for a certain 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 and ions act as ligands.
Thus, when N-cholinergic receptors are activated, sodium channels are activated.
Calcium permeability is initiated by neuronal acetylcholine-gated, glutamate-gated (NMDA and AMPA/kainate-type) receptors and purine receptors.
GABA A receptors are coupled to chloride ion 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.
Thus, protein kinases A, C, G, phosphorylating cation channel proteins, change their permeability.
Mechanically controlled ion channels.
Mechanically gated ion channels change their conductance to ions either by changing the tension of the lipid bilayer 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 characteristics:
time filled with water;
gate mechanism;
stretch sensor.
When a channel is activated, ions move along a concentration gradient.
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 the large domain, and the β subunit is the small domain. During ion transport, large subunits are phosphorylated and ions move through them.
Sodium, potassium ATPase plays a critical 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 and the generation of action potentials;
provides Na + coupled transport of most organic substances across the membrane (secondary active transport);
significantly affects H2O homeostasis.
Sodium, a potassium ATPase, makes the most important contribution to the formation of ionic asymmetry in extra- and intracellular spaces.
The gradual operation of the sodium and potassium pump ensures an unequal exchange of potassium and sodium across the membrane.
Ca + -ATPase (pump).
There are two families of Ca 2+ pumps responsible for the removal of Ca 2+ ions from the cytoplasm: Ca 2+ pumps of the plasmalemma and Ca 2+ pumps of the endoplasmic reticulum.
Although they belong to the same family of proteins (the so-called P-class ATPases), these pumps show some differences in structure, functional activity and pharmacology.
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 higher - 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 plasma membrane Ca 2+ pump is controlled directly by Ca 2+: an increase in the concentration of free calcium in the cytosol activates the Ca 2+ pump.
At rest, there is almost no diffusion through calcium ion channels.
Ca-ATPase transports Ca from the cell to the extracellular environment against its concentration gradient. Along a 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 endoplasmic reticulum calcium pump (SERCA) ensures the removal of calcium from the cytosol into the endoplasmic reticulum - a calcium “depot” 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 now been described.
SERCA1 subtypes are concentrated exclusively in fast skeletal muscles; SERCA2 pumps are widely distributed in other tissues. The significance of SERCA3 pumps is less clear.
SERCA2 proteins are divided into two different isoforms: SERCA2a, characteristic of cardiomyocytes and smooth muscles, and SERCA2b, characteristic of brain tissue.
An increase in cytosolic Ca 2+ activates the uptake of calcium ions into the endoplasmic reticulum, while an increase in free calcium within the endoplasmic reticulum inhibits SERCA pumps.
H+ K+ -ATPase (pump).
With the help of this pump (as a result of the hydrolysis of one ATP molecule), two potassium ions are transported from the extracellular space into the cell and two H+ ions from the cytosol into the extracellular space during the hydrolysis of one molecule in the parietal cells of the gastric mucosa. This mechanism underlies the formation of hydrochloric acid in the stomach.
Ion pump classF.
Mitochondrial ATPase. Catalyzes the final stage of ATP synthesis. Mitochondrial crypts contain ATP synthase, which couples oxidation in the Krebs cycle and phosphorylation of ADP to ATP.
Ion pump classV.
Lysosomal H + -ATPases (lysosomal proton pumps) - proton pumps that provide transport of H + from the cytosol to a number of organelles - lysosomes, 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 asymmetrical transmembrane! gradient for Na + and K + at rest.
Sodium outside the cell (145 mmol/l) is 10 times more than in the cell (14 mmol/l).
There is approximately 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:
homeostatic by the work of Na + /K + -nacoca;
forms an outgoing potassium current at rest (leakage channel);
forms resting potential;
the work of any potassium channels (voltage-dependent, calcium-dependent, ligand-dependent) is aimed at the formation of an outgoing potassium current.
This either returns the state of the membrane to its original level (activation of voltage-dependent channels during the repolarization phase), or hyperpolarizes the membrane (calcium-dependent, ligand-dependent channels, including those activated by second messenger systems).
Please keep 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 channel always causes an inward sodium current;
the movement of sodium across the membrane is almost always carried out by passive transport;
in epithelial cells that form the walls 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, which, upon activation, provide an incoming sodium current, and in the basement membrane - a large number of sodium, potassium pumps that pump sodium out of the cell. This 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 an electrochemical gradient leads to the accumulation of energy, which is used for 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 messenger in the implementation of the signal.
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 (the endoplasmic reticulum is the “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 concentration of calcium in the cytosol.
The low level of calcium in the cytosol of the cell is maintained by Ca 2+ -ATPase, Na + /Ca 2+ -exchangers, and 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+ stores.
3. Low chlorine levels in the cage.
In the cell at rest, the chlorine content (8 mmol/l) is more than 10 times lower than outside the cell (110 mmol/l).
This state is maintained by the work 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 to chlorine. When voltage- and ligand-gated chloride channels are activated, the ion enters the cytosol through the channel by passive transport.
In addition, the entry of chlorine into the cytosol is formed due to the Na + /K + /2CH cotransporter and the CH-HCO 3 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 bioelectrical phenomena in organs and tissues that encode information and determine the functional state of these structures and their transition from one functional state to another.
Ion channels (IC) are membrane molecular structures formed by integral (transmembrane) proteins that penetrate the cell membrane across the cell membrane in the form of several loops and form a through channel (pore) in the membrane. Channel proteins consist of subunits that form a structure with a complex spatial configuration, in which, in addition to the pore, there are usually additional molecular systems: opening, closing, selectivity, inactivation, reception and regulation. ICs can have not one, but several sites (sites) for binding to control substances (ligands).
ICs consist of proteins of complex structure (channel-forming proteins).
IR proteins have a certain conformation, forming a transmembrane pore, and are “sewn” into the lipid layer of the membrane. A channel protein complex can consist of either one protein molecule or several protein subunits, identical or different in structure. These subunits can be encoded by different genes, synthesized separately on ribosomes, and then assembled into a complete channel. In another case, the channel may be a single polypeptide that crosses the membrane several times in the form of loops. At the beginning of the 21st century, more than 400 channel-forming proteins are known, for the biosynthesis of which 1-2% of the human genome is used.
Domains are individual, compactly formed parts of a channel protein or subunits. Segments are parts of a channel-forming protein that are coiled and stitch the membrane. The terminal domains of the channelformer protein (N- and C-terminal domains) can protrude from the membrane both outside and inside the cell.
Almost all ICs contain in their subunits regulatory domains, capable of binding to various control substances (regulatory molecules) and thereby changing the state or properties of the channel. In voltage-activated IR, one of the transmembrane segments contains a special set of amino acids with positive charges and works as electric potential sensor membranes. When the potential changes, such a sensor changes the state of the channel from open to closed or vice versa. Thus, IC can be controlled by certain external influences, this is their important property.
IC may also include accessory subunits, performing modulatory, structural or stabilizing functions. One class of such subunits is intracellular, located entirely in the cytoplasm, and the second is membrane-bound, because they have transmembrane domains that span the membrane.
Classification of ion channels:
By activation type
-Voltage dependent
-Ligand dependent
Mechanically activated
By selectivity
-Selective (Na, K, Ca, Cl)
-Non-selective
By kinetics
-Fast
-Slow
Mixed
It is a voltage-gated ion channel that provides a rapid increase in sodium conductance, responsible for the depolarization phase during the development of action potentials in nerve and muscle cells. Channels isolated from mammalian tissues have a molecular weight of ~335,000. Na+ channels interact with various toxins, in particular tetrodotoxin, saxitoxin and scorpion α-toxin, which bind very strongly to channel proteins and can be used in quantitative biochemical measurements.
Potassium channel
Voltage-gated K channels are located in both the plasma membrane and the sarcoplasmic reticulum. A common property of these channels is sensitivity to the inhibitory effects of tetraethylammonium, 4-aminopyridine and Cs, although the effectiveness of these inhibitors on different channel subtypes varies significantly. These channels are activated by depolarization and repolarize the membrane during an action potential. The speed of their inactivation is low - from 100 ms to several seconds.
5. The concept of excitability. Parameters of excitability of the neuromuscular system: threshold of irritation (rheobase), useful time (chronaxy). Dependence of the strength of irritation on the time of its action (Goorweg-Weiss curve). Refractoriness.
Excitability- this is the ability (property) of some physiological systems to respond to external or internal influence with a specialized response - the generation of an action potential.
Cells capable of excitation (in the human body) - muscle, nerve, secretory - are called excitable. All other cells are irritable. It follows from this that irritability is more general property living systems, while excitability is a private and specialized manifestation of irritability.
For any excitable system there is its own minimum stimulus strength that causes excitation. She got the name threshold or rheobase.
Any stimulus must act for at least a certain time in order to cause an excitation reaction; this time is called latent or useful time.
Chronaxia - This special case useful time of action of a stimulus of 2 thresholds (2 rheobases).
Lability– a measure of excitability or the maximum rhythm of impulses that an excitable system can reproduce per unit time. The magnitude of lability is inversely proportional to the duration of the absolute refractory phase, i.e. 1/ARF (sec).
Law duration of irritation. The tissue response depends on the duration of stimulation, but is carried out within certain limits and is directly proportional. There is a relationship between the strength of irritation and the time of its action. This relationship is expressed as a force-time curve. This curve is called the Goorweg-Weiss-Lapik curve. The curve shows that no matter how strong the stimulus, it must act for a certain period of time. If the time period is short, then the response does not occur. If the stimulus is weak, then no matter how long it acts, a response does not occur. The strength of the stimulus gradually increases, and at a certain moment a tissue response occurs. This force reaches a threshold value and is called rheobase (the minimum force of stimulation that causes a primary response). The time during which a current equal to the rheobase operates is called useful time.
Force-time/duration graph (Goorweg-Weiss-Lapick curve)
Refractoriness– (physiological property of excitable tissues) a temporary decrease in excitability simultaneously with excitation occurring in the tissue. Refractoriness can be absolute (there is no response to any stimulus) and relative (excitability is restored, and the tissue responds to a subthreshold or suprathreshold stimulus);
6. Ion pumps (ATPases): K+-Na+-e, Ca2+-e (plasmolemma and sarcoplasmic reticulum). N+-K+-lbmennik.
Ligand-gated channels are ion channels located in the postsynaptic membrane at neuromuscular junctions. The binding of a mediator to these channels on the outside of the membrane causes changes in their conformation - the channels open, allowing ions to pass through the membrane and thereby changing the membrane potential. Unlike voltage-gated channels, which are responsible for the occurrence of action potentials and transmitter release, ligand-gated channels are relatively insensitive to changes in membrane potential and therefore are not capable of self-reinforcing all-or-nothing excitation. Instead they generate electrical signal, the strength of which depends on the intensity and duration of the external chemical signal, i.e. depends on how much transmitter is released into the synaptic cleft and how long it remains there.
Receptors associated with channels are specific, like enzymes, only in relation to certain ligands and therefore respond to the influence of only one transmitter - the one that is released from the presynaptic terminal; other mediators have no effect.
Channels of different types are characterized by different ion specificity: some can selectively allow sodium ions to pass through, others - potassium ions, etc.; there may also be those that are less selective towards various cations, but do not allow anions to pass through. However, ion specificity is constant for a given postsynaptic membrane: usually all channels in a synapse have the same selectivity.
Of all the ligand-gated ion channels, the nicotinic acetylcholine receptor is the most studied.
There are many other types of MK, they are activated by various mediators (serotonin, glycine, gamma-aminobutyric acid - GABA, etc.) and all these main types of MK are divided into many subtypes. Regarding sensory systems, the most important MKs, found in olfactory and photoreceptor cells, are sensitive to cyclic nucleotides (CNNs). The structure of the CNC gate canals will be described. Unlike n-AChR channels, the subunit protein forms 6 transmembrane segments, and the entire channel consists of four subunits.