Ion channel properties
Selectivity is the selective, increased permeability of IR for certain ions. For other ions, the permeability is reduced. This selectivity is determined by a selective filter - the narrowest point of the channel pore. The filter, in addition to its 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 area 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 IK to open or close under certain control actions on the channel. A closed channel has a reduced permeability, and an open one - increased. According to this property, IRs can be classified depending on the methods of their discovery: for example, potential-activated, ligand-activated, etc.
Inactivation is the ability of IR, some time after its opening, to automatically lower its permeability even if the activating factor that opened them continues to act. Rapid inactivation is a special process with its own special mechanism, which differs from slow closure of the canal (slow inactivation). Closing (slow inactivation) of the channel occurs due to processes opposite to the processes that ensured its opening, i.e. by changing the conformation of the channel protein. But, for example, in potential-activated channels, rapid inactivation occurs with the help of a special molecular "plug-plug", reminiscent of 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 plugs the inner opening of the canal from the side of the cytoplasm. That is why voltage-dependent ICs for sodium, which ensure the development of the action potential and the movement of the nerve impulse, can let sodium ions into the cell only for a few milliseconds, and then they automatically close with their molecular plugs, despite the fact that the depolarization that opens them continues to act. Another mechanism of IK inactivation can be modification of the intracellular canal opening with additional subunits.
Blocking is the ability of IC under the influence of blocking substances to fix one of its states and not respond to usual control influences. In this state, the channel simply stops giving responses to control actions. The blockage is caused by blocker substances, which may be called antagonists, blockers, or lytic agents. Antagonists are substances that interfere with the activating effect of other substances on IC. Such substances are able to bind well to the receptor site of the IC, but they are not able to change the state of the channel, to cause its response. It turns out the blockade of the receptor and, along with it, the blockade of the IC. It should be remembered that antagonists do not necessarily cause a complete blockade of the receptor and its IC, they can act weaker and only inhibit (depress) the channel, but do not completely stop it.Agonists-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 interfere with 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 - adrenergic blockers; histamine - histamine blockers, etc. Many blockers are used for therapeutic purposes as drugs. Lytic are the same blockers, the term is older and is used synonymously for a blocker: anticholinergic, adrenolytic, etc.
Plasticity is the ability of IR to change its properties, its characteristics. The most common mechanism providing 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 the channel proteins, and the channel changes its properties. For example, it is fixed in a permanently closed state, or, conversely, in an open state.
All channels present in living tissues, and now we know several hundred varieties of channels, can be divided into two main types. The first type is channels of rest, which spontaneously open and close without any external influences. They are important for the generation of the resting membrane potential. The second type is the so-called gate channels, or portal channels(from the word "gate") . At rest, these channels are closed and can be opened under the influence of certain stimuli. Some types of such channels take part in the generation of action potentials.
Most ion channels are characterized by selectivity(selectivity), that is, only certain ions pass through a certain type of channels. On this basis, sodium, potassium, calcium, chlorine channels are distinguished. The selectivity of the channels is determined by the size of the pore, the size of the ion and its hydration shell, the charge of the ion, and the charge of the inner surface of the channel. However, there are also non-selective channels that can pass two types of ions at once: for example, potassium and sodium. There are channels through which all ions and even larger molecules can pass.
There is a classification of ion channels by activation method(fig. 9). Some channels specifically respond to physical changes in the cell membrane of a neuron. The most prominent representatives of this group are potential-activated channels... Examples are sodium, potassium, and calcium ion channels that are sensitive to the potential on the membrane, which are responsible for the formation of an action potential. These channels open at a certain potential across the membrane. So, sodium and potassium channels open at a potential of about -60 mV (the inner surface of the membrane is negatively charged compared to the outer surface). Calcium channels open at a potential of -30 mV. The group of channels activated by physical changes includes
Fig 9. Methods for activating ion channels
(A) Ionic channels activated by changes in membrane potential or membrane stretching. (B) Ionic channels activated by chemical agents (ligands) from the extracellular or intracellular side.
also mechano-sensitive channels that respond to mechanical stress (stretching or deformation of the cell membrane). Ionic channels of another group open when chemicals activate special receptor binding centers on the channel molecule. Such ligand-activated channels are subdivided into two subgroups, depending on whether their receptor centers are intracellular or extracellular. Ligand-activated channels that respond to extracellular stimuli are also called ionotropic receptors. Such channels are sensitive to mediators and are most directly involved in the transmission of information in synaptic structures. Ligand-activated channels that are activated from the cytoplasmic side include channels that are sensitive to changes in the concentration of specific ions. For example, calcium-activated potassium channels are activated by a local increase in intracellular calcium concentration. Such channels play an important role in the repolarization of the cell membrane during the completion of the action potential. In addition to calcium ions, cyclic nucleotides are typical representatives of intracellular ligands. Cyclic GMF, for example, is responsible for the activation of sodium channels in the retinal rods. This type of channel plays a fundamental role in the work of the visual analyzer. Phosphorylation / dephosphorylation of certain parts of its protein molecule under the action of intracellular enzymes - protein kinases and protein phosphatases - is a separate type of modulation of the channel by binding an intracellular ligand.
The presented classification of channels by the method of activation is largely arbitrary. Some ion channels can only be activated with a few treatments. For example, calcium-activated potassium channels are also sensitive to potential changes, and some voltage-activated ion channels are sensitive to intracellular ligands.
According to modern concepts, biological membranes form the outer membrane of all animal cells and form numerous intracellular organelles. The most characteristic structural feature is that membranes always form closed spaces, and this microstructural organization of membranes allows them to perform critical functions.
The structure and function of cell membranes.
1. The barrier function is expressed in the fact that the membrane with the help of appropriate mechanisms participates in the creation of concentration gradients, preventing free diffusion. In this case, the membrane takes part in the mechanisms of electrogenesis. These include mechanisms for creating resting potential, generation of an action potential, mechanisms for the propagation of bioelectric impulses along homogeneous and inhomogeneous excitable structures.
2. The regulatory function of the cell membrane consists in fine regulation of the intracellular content and intracellular reactions due to the reception of extracellular biologically active substances, which leads to a change in the activity of the membrane enzyme systems and the launch of the mechanisms of secondary “messengers” (“mediators”).
3. Transformation of external stimuli of a non-electrical nature into electrical signals (in receptors).
4. Release of neurotransmitters in synaptic endings.
The thickness of cell membranes (6-12 nm) was determined by modern methods of electron microscopy. Chemical analysis showed that membranes are mainly composed of lipids and proteins, the amount of which is not the same for different types of cells. The difficulty of studying the molecular mechanisms of the functioning of cell membranes is due to the fact that during the isolation and purification of cell membranes, their normal functioning is disrupted. Currently, we can talk about several types of models of the cell membrane, among which the most widespread is the liquid-mosaic model.
According to this model, the membrane is represented by a bilayer of phospholipid molecules oriented in such a way that the hydrophobic ends of the molecules are inside the bilayer, while the hydrophilic ends are directed to the aqueous phase. This structure is ideal for the formation of the separation of two phases: extra- and intracellular.
In the phospholipid bilayer, globular proteins are integrated, the polar regions of which form a hydrophilic surface in the aqueous phase. These integrated proteins perform various functions, including receptor, enzymatic, form ion channels, are membrane pumps and carriers of ions and molecules.
Some protein molecules freely diffuse in the plane of the lipid layer; in the normal state, parts of protein molecules emerging on opposite sides of the cell membrane do not change their position.
Membrane electrical characteristics:
Capacitive properties are mainly determined by the phospholipid bilayer, which is impermeable to hydrated ions and at the same time thin enough (about 5 nm) to ensure efficient separation and accumulation of charges and electrostatic interaction of cations and anions. In addition, the capacitive properties of cell membranes are one of the reasons that determine the temporal characteristics of electrical processes occurring on cell membranes.
Conductivity (g) is the reciprocal of electrical resistance and is equal to the ratio of the total transmembrane current for a given ion to the value that caused its transmembrane potential difference.
Various substances can diffuse through the phospholipid bilayer, and the degree of permeability (P), i.e., the ability of the cell membrane to pass these substances, depends on the difference in the concentration of the diffusing substance on both sides of the membrane, its solubility in lipids and the properties of the cell membrane.
The conductivity of a membrane is a measure of its ionic permeability. An increase in conductivity indicates an increase in the number of ions passing through the membrane.
Structure and function of ion channels... Ions Na +, K +, Ca2 +, Cl- penetrate into the cell and go out through special channels filled with liquid. The size of the channels is quite small.
All ion channels are classified into the following groups:
- By selectivity:
a) Selective, i.e. specific. These channels are permeable to strictly defined ions.
b) Low-selective, non-specific, not having a certain ionic selectivity. There are few of them in the membrane.
- By the nature of the passed ions:
a) potassium
b) sodium
c) calcium
d) chlorine
- By the rate of inactivation, i.e. closing:
a) rapidly inactivating, i.e. quickly turning into a closed state. They provide a rapidly increasing decrease in MF and an equally fast recovery.
b) slow-moving. Their opening causes a slow decrease in the MP and its slow recovery.
4. By opening mechanisms:
a) potential-dependent, i.e. those that open at a certain level of membrane potential.
b) chemodependent, which open when the chemoreceptors of the cell membrane are exposed to physiologically active substances (neurotransmitters, hormones, etc.).
It has now been established that ion channels have the following structure:
1. Selective filter located at the mouth of the channel. It ensures the passage of strictly defined ions through the channel.
2. Activation gates, which open at a certain level of membrane potential or the action of the corresponding PAV. The activation gates of voltage-dependent channels have a sensor that opens them at a certain level of the MP.
3. Inactivation gates, which ensure the closure of the channel and the termination of the conduction of ions through the channel at a certain level of the MF (Fig).
Nonspecific ion channels have no gates.
Selective ion channels can be in three states, which are determined by the position of the activation (m) and inactivation (h) gates:
1.Closed, when the activation is closed, and the inactivation is open.
2. When activated, both gates are open.
3.Inactivated, the activation gate is open and the inactivation gate is closed
Ion Channel Functions:
1. Potassium (at rest) - generation of rest potential
2. Sodium - generation of action potential
3. Calcium - Slow Action Generation
4. Potassium (delayed rectification) - ensuring repolarization
5. Potassium calcium-activated - limiting depolarization due to the current Ca + 2
The function of ion channels is studied in various ways. The most common is the voltage-clamp method. The essence of the method lies in the fact that with the help of special electronic systems during the experiment, the membrane potential is changed and fixed at a certain level. In this case, the value of the ionic current flowing through the membrane is measured. If the potential difference is constant, then, in accordance with Ohm's law, the current is proportional to the conductivity of the ion channels. In response to stepwise depolarization, certain channels are opened, the corresponding ions enter the cell along an electrochemical gradient, that is, an ionic current arises, which depolarizes the cell. This change is registered using a control amplifier and an electric current is passed through the membrane, equal in magnitude, but opposite in direction to the membrane ionic current. In this case, the transmembrane potential difference does not change.
The study of the function of individual channels is possible by the method of local clamping of potential "path-clamp". A glass microelectrode (micropipette) is filled with saline, pressed against the membrane surface and a slight vacuum is applied. In this case, part of the membrane is sucked into the microelectrode. If an ion channel appears in the suction zone, the activity of a single channel is recorded. The system of stimulation and registration of channel activity differs little from the voltage fixation system.
The current through a single ion channel has a rectangular shape and is the same in amplitude for different types of channels. The duration of the channel's stay in the open state has a probabilistic character, but depends on the value of the membrane potential. The total ionic current is determined by the probability of being in the open state in each specific period of time for a certain number of channels.
The outer part of the canal is relatively accessible for study; the study of the inner part presents significant difficulties. P. G. Kostyuk developed a method of intracellular dialysis, which allows studying the function of the input and output structures of ion channels without the use of microelectrodes. It turned out that the part of the ion channel opened into the extracellular space differs in its functional properties from the part of the channel facing the intracellular environment.
It is the ion channels that provide two important properties of the membrane: selectivity and conductivity.
Selectivity, or selectivity, of the channel is provided by its special protein structure. Most of the channels are electrically controlled, i.e., their ability to conduct ions depends on the value of the membrane potential. The channel is heterogeneous in its functional characteristics, especially for protein structures located at the entrance to the channel and at its exit (the so-called gate mechanisms).
Let us consider the principle of operation of ion channels using the example of a sodium channel. The sodium channel is believed to be closed at rest. When the cell membrane is depolarized to a certain level, the m-activation gates are opened (activation) and the flow of Na + ions into the cell increases. A few milliseconds after the opening of the m-gate, the h-gate located at the exit of the sodium channels closes (inactivation). Inactivation develops in the cell membrane very quickly and the degree of inactivation depends on the magnitude and duration of the depolarizing stimulus.
When a single action potential is generated in a thick nerve fiber, the change in the concentration of Na + ions in the internal environment is only 1/100000 of the internal content of Na ions in the giant squid axon.
In addition to sodium, other types of channels are installed in cell membranes that are selectively permeable for individual ions: K +, Ca2 +, and there are varieties of channels for these ions.
Hodgkin and Huxley formulated the principle of "independence" of channels, according to which the flows of sodium and potassium through the membrane are independent of each other.
The conductivity property of different channels is not the same. In particular, for potassium channels, the inactivation process does not exist, as for sodium channels. There are special potassium channels that are activated with an increase in intracellular calcium concentration and depolarization of the cell membrane. Activation of potassium-calcium-dependent channels accelerates repolarization, thereby restoring the initial value of the resting potential.
Calcium channels are of particular interest. The incoming calcium current is usually not large enough to depolarize the cell membrane normally. Most often, calcium entering the cell acts as a “messenger”, or a secondary mediator. The activation of calcium channels is provided by depolarization of the cell membrane, for example, by the incoming sodium current.
The process of inactivation of calcium channels is rather complicated. On the one hand, an increase in the intracellular concentration of free calcium leads to inactivation of calcium channels. On the other hand, proteins of the cytoplasm of cells bind calcium, which allows maintaining a stable value of calcium current for a long time, albeit at a low level; in this case, the sodium current is completely suppressed. Calcium channels play an essential role in heart cells. Electrogenesis of cardiomyocytes is discussed in Chapter 7. Electrophysiological characteristics of cell membranes are investigated using special methods.
The structure and function of ion channels. Ions Na +, K +, Ca 2+, Cl - penetrate into the cell and go out through special channels filled with liquid. The channel size is rather small (diameter 0.5-0.7 nm). Calculations show that the total channel area occupies an insignificant part of the cell membrane surface.
The function of ion channels is studied in various ways. The most common is the voltage-clamp method (Figure 2.2). The essence of the method lies in the fact that with the help of special electronic systems during the experiment, the membrane potential is changed and fixed at a certain level. In this case, the value of the ionic current flowing through the membrane is measured. If the potential difference is constant, then, in accordance with Ohm's law, the current is proportional to the conductivity of the ion channels. In response to stepwise depolarization, certain channels are opened, the corresponding ions enter the cell along an electrochemical gradient, that is, an ionic current arises, which depolarizes the cell. This change is registered using a control amplifier and an electric current is passed through the membrane, equal in magnitude, but opposite in direction to the membrane ionic current. In this case, the transmembrane potential difference does not change. The combined use of the potential clamping method and specific ion channel blockers has led to the opening of various types of ion channels in the cell membrane.
At present, many types of channels have been established for various ions (Table 2.1). Some of them are very specific, the second, in addition to the main ion, can pass other ions.
The study of the function of individual channels is possible by the method of local clamping of potential "path-clamp"; rice. 2.3, A). A glass microelectrode (micropipette) is filled with saline, pressed against the membrane surface and a slight vacuum is applied. In this case, part of the membrane is sucked into the microelectrode. If an ion channel appears in the suction zone, the activity of a single channel is recorded. The system of stimulation and registration of channel activity differs little from the voltage fixation system.
Table 2.1. The most important ion channels and ion currents of excitable cells
Note. TEA - tetraethylammonium; TTX - tetrodotoxin.
The outer part of the canal is relatively accessible for study; the study of the inner part presents significant difficulties. P. G. Kostyuk developed the method of intracellular dialysis, which allows studying the function of the input and output structures of ion channels without the use of microelectrodes. It turned out that the part of the ion channel opened into the extracellular space differs in its functional properties from the part of the channel facing the intracellular environment.
It is the ion channels that provide two important properties of the membrane: selectivity and conductivity.
Selectivity, or selectivity, the channel is provided by its special protein structure. Most of the channels are electrically controlled, i.e., their ability to conduct ions depends on the value of the membrane potential. The channel is heterogeneous in its functional characteristics, especially for protein structures located at the entrance to the channel and at its exit (the so-called gate mechanisms).
5. The concept of excitability. Parameters of excitability of the neuromuscular system: irritation threshold (rheobase), useful time (chronaxia). Dependence of the strength of irritation on the time of its action (Goorweg-Weiss curve). Refractoriness.
Excitability- the ability of a cell to respond to stimulation by the formation of AP and a specific reaction.
1) the phase of the local response - partial depolarization of the membrane (entry of Na + into the cell). If you apply a small irritant, then the answer is stronger.
Local depolarization is the phase of exaltation.
2) the phase of absolute refractoriness - the property of excitable tissues not to form PD for any stimulus of any strength
3) the phase of relative refractoriness.
4) the phase of slow repolarization - irritation - again a strong response
5) the phase of hyperpolarization - less excitability (subnormal), the stimulus should be large.
Functional lability- assessment of tissue excitability through the maximum possible number of APs per unit time.
Excitation laws:
1) the law of force - the force of the stimulus must be threshold or above-threshold (the minimum value of the force that causes excitement). The stronger the stimulus, the stronger the excitement - only for tissue associations (nerve trunk, muscle, with the exception of SMC).
2) the law of time - a long acting stimulus should be sufficient for the onset of excitement.
The relationship between force and time is inversely proportional between the minimum time and the minimum force. The minimum force - rheobase - is the force that causes excitement and does not depend on the duration. Minimum time is good time. Chronaxia is the excitability of a particular tissue, the time at which arousal occurs is equal to two rheobases.
The greater the strength, the greater the response to a certain value.
Factors that create MSP:
1) the difference in the concentration of sodium and potassium
2) different permeability to sodium and potassium
3) the work of the Na-K pump (3 Na + is removed, 2 K + is returned).
The relationship between the strength of the stimulus and the duration of its impact, necessary for the emergence of a minimal response of a living structure, can be very well traced on the so-called force-time curve (Goorweg-Weiss-Lapik curve).
From the analysis of the curve it follows that, no matter how great the strength of the stimulus, if the duration of its action is insufficient, there will be no response (points to the left of the ascending branch of the hyperbola). A similar phenomenon is observed with prolonged action of subthreshold stimuli. The minimum current (or voltage) that can cause excitation is called Lapik rheobase (a segment of the ordinate OA). The smallest time interval during which a current equal in strength to a doubled rheobase causes excitation in the tissue is called chronaxia (a segment of the abscissa OF), which is an indicator of the threshold duration of stimulation. Chronaxia is measured in δ (thousandths of a second). By the magnitude of chronaxia, one can judge the rate of onset of excitation in the tissue: the less chronaxia, the faster excitement arises. Chronaxia of human nerve and muscle fibers is equal to thousandths and ten-thousandths of a second, and chronaxia of so-called slow tissues, for example, muscle fibers of a frog's stomach, is equal to hundredths of a second.
Determination of chronaxia of excitable tissues has become widespread not only in experiment, but also in the physiology of sports, in the clinic. In particular, by measuring the chronaxia of the muscle, the neurologist can establish the presence of motor nerve damage. It should be noted that the stimulus can be strong enough, have a threshold duration, but a low rate of increase in time to the threshold value; excitation in this case does not arise. The adaptation of excitable tissue to a slowly growing stimulus is called accommodation. Accommodation is due to the fact that during the increase in the strength of the stimulus in the tissue, active changes have time to develop, increasing the threshold of irritation and preventing the development of excitation. Thus, the rate of increase in stimulation over time, or the gradient of stimulation, is essential for the onset of arousal.
Irritation gradient law. The reaction of a living entity to a stimulus depends on the gradient of stimulation, i.e., on the urgency or steepness of the growth of the stimulus in time: the higher the gradient of stimulation, the stronger (up to certain limits) the response of the excitable formation.
Consequently, the laws of irritation reflect the complex relationship between the stimulus and the excitable structure during their interaction. For excitation to occur, the stimulus must have a threshold strength, have a threshold duration and have a certain rate of increase in time.
6. Ion pumps (ATP-ases): K + -Na +, Ca2 + (plasmolemma and sarcoplasmic reticulum), H + –K + -exchanger.
According to modern concepts, biological membranes have ion pumps operating at the expense of the free energy of ATP hydrolysis - special systems of integral proteins (transport ATPases).
Currently, there are three types of electrogenic ion pumps that actively transfer ions across the membrane (Fig. 13).
The transfer of ions by transport ATPases occurs due to the conjugation of transfer processes with chemical reactions, due to the energy of cell metabolism.
During the work of K + -Na + -ATPase, due to the energy released during the hydrolysis of each ATP molecule, two potassium ions are transferred into the cell, and at the same time three sodium ions are pumped out of the cell. Thus, an increased concentration of potassium ions in the cell and a reduced sodium concentration in the cell is created in comparison with the intercellular environment, which is of great physiological importance.
Signs of a "bionpump":
1. Movement against the gradient of electrochemical potential.
2. The flow of a substance is associated with the hydrolysis of ATP (or other energy source).
3. asymmetry of the transport vehicle.
4. The in vitro pump is capable of hydrolyzing ATP only in the presence of those ions that it carries in vivo.
5. When the pump is built into an artificial environment, it is able to maintain selectivity.
The molecular mechanism of operation of ionic ATPases is not fully understood. Nevertheless, the main stages of this complex enzymatic process can be traced. In the case of K + -Na + -ATPase, there are seven stages of ion transfer associated with ATP hydrolysis.
The diagram shows that the key stages of the enzyme are:
1) the formation of a complex of the enzyme with ATP on the inner surface of the membrane (this reaction is activated by magnesium ions);
2) binding by a complex of three sodium ions;
3) phosphorylation of the enzyme with the formation of adenosine diphosphate;
4) flip-flop (flip-flop) of the enzyme inside the membrane;
5) the reaction of ion exchange of sodium for potassium, occurring on the outer surface of the membrane;
6) reverse flip of the enzyme complex with the transfer of potassium ions into the cell;
7) the return of the enzyme to its original state with the release of potassium ions and inorganic phosphate (P).
Thus, during a full cycle, three sodium ions are released from the cell, the cytoplasm is enriched with two potassium ions, and one ATP molecule is hydrolyzed.
Ligand-gated channels are ion channels located in the postsynaptic membrane at neuromuscular junctions. Binding of the mediator to these channels from the outside of the membrane causes changes in their conformation - the channels open, passing ions through the membrane and thereby changing the membrane potential. Unlike voltage-dependent channels, which are responsible for the emergence of an action potential and release of a mediator, ligand-dependent channels are relatively insensitive to changes in membrane potential and therefore are not capable of self-reinforcing all-or-nothing excitation. Instead, they generate an electrical signal, the strength of which depends on the intensity and duration of the external chemical signal, i.e. on how much mediator is excreted 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 action of only one mediator - the one that is released from the presynaptic terminal; other mediators have no effect.
For channels of different types, different ionic specificity is characteristic: some can selectively pass sodium ions, others - potassium, etc., there may be those that are not very selective with respect to various cations, but do not pass anions. However, ionic specificity is constant for a given postsynaptic membrane: usually all channels in a synapse have the same selectivity.
Of all the ligand-dependent ion channels, the nicotinic acetylcholine receptor is the most studied.
Many other types of MK are known, they are activated by various mediators (serotonin, glycine, gamma-aminobutyric acid - GABA, etc.), and all these main types of MK are subdivided into many subtypes. In terms of sensory systems, the most important MCs found in olfactory and photoreceptor cells are sensitive to cyclic nucleotides (CNS). The structure of the CNZ-portal canals will be described. Unlike n-AChP channels, the subunit protein forms 6 transmembrane segments, and the whole channel consists of four subunits.
