Action potential (AP) is a short-term amplitude change in the resting membrane potential (RMP) that occurs when a living cell is excited. Essentially, this is an electrical discharge - a rapid, short-term change in potential in a small area of the membrane of an excitable cell (neuron or muscle fiber), as a result of which the outer surface of this area becomes negatively charged in relation to neighboring areas of the membrane, while its inner surface becomes positively charged in relation to to adjacent areas of the membrane. The action potential is the physical basis of a nerve or muscle impulse that plays a signaling (regulatory) role.
general characteristics
Action potentials can differ in their parameters depending on the type of cell and even on different parts of the membrane of the same cell. The most typical example of differences is the action potential of the heart muscle and the action potential of most neurons. Nevertheless, the basis of any action potential is the following phenomena:
- “The membrane of a living cell is polarized” - its inner surface is charged negatively in relation to the outer one due to the fact that in the solution at its outer surface there is a larger number of positively charged particles (cations), and at the inner surface there is a larger number of negatively charged particles (anions).
- “A membrane has selective permeability” - its permeability to different particles (atoms or molecules) depends on their size, electrical charge and chemical properties.
- “The membrane of an excitable cell is capable of quickly changing its permeability for a certain type of cations, causing a transition of positive charge from the outside to the inside
The first two properties are characteristic of all living cells. The third is a feature of excitable tissue cells and the reason why their membranes are able to generate and conduct action potentials.
The main mathematical model describing the generation and transmission of action potentials is the Hodgkin-Huxley model.
Vascular endothelium
The endothelium is a thin layer of simple squamous epithelial cells lining the interior of blood and lymph vessels. The endothelium, that line of blood vessels, is known as the vascular endothelium, which is subject to and must withstand the forces of blood flow and blood pressure from the cardiovascular system.
In order to withstand these cardiovascular forces, endothelial cells must simultaneously have a structure capable of withstanding circulatory forces while maintaining a certain level of plasticity in the strength of their structure. This plasticity in the structural strength of the vascular endothelium is important for the overall function of the cardiovascular system.
Endothelial cells in blood vessels can change the strength of their structures to maintain the vascular tone of the blood vessel they line, prevent vascular stiffness, and even help regulate blood pressure in the cardiovascular system. Endothelial cells accomplish these feats by using depolarization to change their structural strength.
When endothelial cells undergo depolarization, the result is a marked reduction in the rigidity and structural strength of the cell, altering the network of fibers that provide these cells with their structural support. Depolarization of the vascular endothelium is important not only for the structural integrity of endothelial cells, but also for the ability of the vascular endothelium to help regulate vascular tone, prevent vascular stiffness, and regulate blood pressure.
Phases
Five phases of development of PD can be clearly distinguished:
Rising (depolarization)
The occurrence of an action potential (AP) is associated with an increase in the permeability of the membrane for sodium ions (20 times compared to the permeability for K +, and 500 times compared to the initial permeability of Na +) and a subsequent increase in the diffusion of these ions along the concentration gradient into the cell, leads to a change (decrease) in membrane potential.
A decrease in membrane potential leads to an increase in membrane permeability to sodium by opening voltage-gated sodium channels, and an increase in permeability is accompanied by increased diffusion of sodium into the cytoplasm, which causes even more significant depolarization of the membrane. Due to the presence of positive feedback, depolarization of the membrane during excitation occurs with acceleration and the flow of sodium ions into the cell increases all the time. The intensity of the flow of potassium ions directed from the cell outwards in the first moments of excitation remains at the beginning. The increased flow of positively charged sodium ions into the cell first causes the disappearance of excess negative charge on the inner surface of the membrane, and then leads to recharging of the membrane. The influx of sodium ions occurs until the inner surface of the membrane acquires a positive charge sufficient to balance the sodium concentration gradient and stop its further passage into the cell. The sodium occurrence of PD is confirmed by experiments with changes in the external and internal concentrations of this ion. It was shown that a tenfold change in the concentration of sodium ions in the external or internal environment of the cell corresponds to a change in PD of 58 mV. When sodium ions were completely removed from the fluid surrounding the cell, PD did not occur. Thus, it has been established that AP occurs as a result of excess, compared to rest, diffusion of sodium ions from the surrounding fluid into the cell. The period during which the membrane permeability for sodium ions increases when sodium channels open is short (0.5-1 ms), followed by an increase in membrane permeability for potassium ions due to the opening of voltage-dependent potassium channels, and, consequently, increased diffusion these ions out of the cell. The “all or nothing” principle According to the “all-or-nothing” law, the cell membrane of an excitable tissue either does not respond to the stimulus at all, or responds with the maximum force possible for it at the moment. The action of the stimulus usually leads to local depolarization of the membrane. This causes the opening of sodium channels, which are sensitive to changes in potential, and through this increases sodium conductance, which leads to even greater depolarization. The existence of such feedback ensures regenerative (renewable) depolarization of the cell membrane. The magnitude of the action potential depends on the strength of the stimulus, and it occurs only when depolarization exceeds a certain limiting level specific for each cell. This phenomenon is called “all or nothing.” However, if depolarization is 50-75% of the limiting value, then a local response may occur in the cell, the amplitude of which is significantly lower than the amplitude of the action potential. The absence of an action potential at the pidboundary level of depolarization is explained by the fact that sodium permeability does not increase sufficiently to cause regenerative depolarization. The level of depolarization that occurs does not cause the opening of new sodium channels, so sodium conductance quickly decreases, and the resting potential in the cell is again established.
Overshoot
Depolarization of the membrane leads to a reversal of the membrane potential (the MP becomes positive).
In the overshoot phase, the Na + current begins to rapidly decrease, which is associated with the inactivation of voltage-dependent Na + channels (the open state time is milliseconds) and the disappearance of the electrochemical Na + gradient. Refractoriness One of the consequences of the disappearance of the Na + gradient is refractoriness - a temporary inability to respond to a stimulus. If the stimulus occurs immediately after the passage of the action potential, then excitability will not occur either with a stimulus strength at the threshold level or with a significantly stronger stimulus. This state of complete inexcitability is called the absolute refractory period. This is followed by a relative refractory period, when a suprathreshold stimulus can cause an action potential with a significantly lower amplitude than normal. An action potential of the usual amplitude under the action of a threshold stimulus can be evoked only after a few milliseconds after the preliminary action potential. The absolute refractory period limits the maximum frequency of generation of action potentials.
Repolarization
An increase in the potassium ion flow directed outward from the cell leads to a decrease in the membrane potential, which in turn causes a decrease in the permeability of the membrane to sodium ions, which, as indicated, is a function of the membrane potential. Thus, the second stage is characterized by the fact that the flow of potassium ions from the cell outward increases, and the counter flow of sodium ions decreases. This membrane repolarization continues until the resting potential is restored—membrane repolarization. After this, the permeability to potassium ions also drops to its original value. Due to the positively charged potassium ions released into the environment, the outer surface of the membrane again acquires a positive potential relative to the internal one.
Trace depolarization and hyperpolarization
In the final phase, the restoration of the resting membrane potential slows down, and trace reactions are recorded in the form of trace depolarization and hyperpolarization, due to the slow restoration of the initial permeability for K + ions.
Depression Verigo
In 1889, a phenomenon in physiology called Verigo's Catholic depression was described. The critical level of depolarization is the level of depolarization at which all sodium channels are already inactivated, and potassium channels work instead. If the degree of current increases even more, then the excitability of the nerve fiber decreases significantly. And the critical level of depolarization under the influence of stimuli goes off scale.
During Verigo's depression, the rate of conduction of excitation decreases and, finally, completely subsides. The cell begins to adapt by changing its functional characteristics.
Spreading
Spread into unmyelinated fibers
In unmyelinated (without pulp) nerve fibers, the AP spreads from point to point, since excitation can be registered as one that gradually “runs” along the entire fiber from its point of origin. Sodium ions entering the excited area serve as a source of electric current for the occurrence of AP in adjacent areas. In this case, the impulse occurs between the depolarized section of the membrane and its non-excited section. The potential difference here is many times higher than necessary for membrane depolarization to reach the maximum level. The speed of pulse propagation in such fibers is 0.5-2 m/s
Spread in myelinated fibers
The nerve processes of most somatic nerves are myelinated.
Only very small areas of them, the so-called node interception (interception of Ranvier), are covered with a normal cell membrane. Such nerve fibers are characterized by the fact that voltage-dependent ion channels are located on the membrane only at the interceptions. In addition, this shell increases the electrical resistance of the membrane. Therefore, when the membrane potential shifts, the current passes through the membrane of the intercepting area, that is, by jumping (saltatory) from one interception to another, which allows you to increase the speed of the nerve impulse, which ranges from 5 to 120 m/s. Moreover, the action potential that arose in one of the nodes of Ranvier causes action potentials in neighboring nodes due to the emergence of an electric field, which causes an initial depolarization in these nodes. The parameters of the EMF field and the distance of its effective action depend on the cable properties of the axon. Types of nerve fibers, impulse conduction speed, depending on myelination
| Type | Diameter (µm) | Myelination | Conduction speed (m/s) | Functional purpose |
| A alpha | 12-20 | strong | 70-120 | Mobile fibers of the somatic NS; proprioceptor sensory fibers |
| A beta | 5-12 | strong | 30-70 | Sensory fibers of skin receptors |
| A gamma | 3-16 | strong | 15-30 | Sensory fibers of proprioceptors |
| A delta | 2-5 | strong | 12-30 | Sensitive fibers of thermoreceptors, nociceptors |
| IN | 1-3 | weak | 3-15 | Preganglionic fibers of the sympathetic nervous system |
| WITH | 0,3-1,3 | absent | 0,5-2,3 | Postganglionic fibers of the sympathetic nervous system; sensory fibers of thermoreceptors, nociceptors of some mechanoreceptors |
What happens during depolarization?
What does such an indicator as the critical level of depolarization mean? In physiology, this means that the nerve cells are already ready to work. The proper functioning of the entire organ depends on the normal, timely change of phases of the action potential.
The critical level (CLL) is approximately 40–50 MV. At this time, the electric field around the membrane decreases. The degree of polarization directly depends on how many sodium channels in the cell are open. The cell at this time is not yet ready to respond, but collects electrical potential. This period is called absolute refractoriness. The phase lasts only 0.004 s in nerve cells, and in cardiomyocytes - 0.004 s.
After passing a critical level of depolarization, superexcitability occurs. Nerve cells can respond even to the action of a subthreshold stimulus, that is, a relatively weak influence of the environment.
Action potential propagation between cells
At a chemical synapse, after the action potential wave reaches the nerve terminal, it causes the release of neurotransmitters from the presynaptic vesicles into the synaptic cleft. Transmitter molecules released from the presynapse bind to receptors on the postsynaptic membrane, resulting in the opening of ion channels in the receptor macromolecules. Ions begin to enter the postsynaptic cell through open channels, change the charge of its membrane, which leads to partial depolarization of the membrane and, as a consequence, provoking the generation of an action potential in the postsynaptic cell.
In the electrical synapse there is no “mediator” of transmission in the form of a neurotransmitter. But the cells are connected to each other using specific protein tunnels - conexons, so ionic currents from the presynaptic cell can stimulate the postsynaptic cell, causing the generation of an action potential in it. Thanks to this structure, the action potential can propagate in both directions and much faster than through a chemical synapse.
- Scheme of the process of nerve signal transmission at a chemical synapse
- Diagram of the structure of an electrical synapse
Repolarization disorder
Early ventricular repolarization syndrome
For some reason, there may be a disruption in repolarization processes. This means that there is a problem with charge restoration. The cell does not have time to “rest” before the next excitation. Various reasons may contribute to this. Taking medications that stimulate the sympathetic nervous system can cause the development of early ventricular repolarization syndrome. Connective tissue diseases (collagenosis), cardiomyopathy, heart defects, coronary heart disease, myocardial hypertrophy and other factors can lead to disturbances in repolarization processes.
Clinically, this may manifest itself as symptoms of the underlying disease, or it may be recorded only on an electrocardiogram. However, no matter how things are with your health, you should consult a doctor. Be healthy!
Action potential in different cell types
Action potential in muscle tissue
The action potential in skeletal muscle cells is similar to the action potential in neurons. Their resting potential is typically -90 mV, which is less than the resting potential of typical neurons. The action potential of muscle cells lasts approximately 2–4 ms, the absolute refractory period is approximately 1–3 ms, and the conduction velocity along the muscle is approximately 5 m/s.
Action potential in cardiac tissue
The action potential of the cells of the working myocardium consists of a phase of rapid depolarization, an initial rapid repolarization, which turns into a phase of slow repolarization (plateau phase), and a phase of rapid final repolarization. The phase of rapid depolarization is caused by a sharp increase in the permeability of the membrane for sodium ions, causes a rapid incoming sodium current, when the membrane potential reaches 30-40 mV it is inactivated and subsequently the calcium ion current plays a major role. Depolarization of the membrane causes activation of calcium channels, resulting in an additional depolarizing incoming calcium current.
The action potential in cardiac tissue plays an important role in coordinating cardiac contractions.
How are impulses transmitted from nerve cells to muscles?
Electrical impulses generated when the membrane is excited are transmitted along nerve fibers at high speed. The speed of the signal is explained by the structure of the axon. The axon is partially enveloped by a sheath. And between the areas with myelin there are nodes of Ranvier.
Thanks to this arrangement of the nerve fiber, a positive charge alternates with a negative one, and the depolarizing current spreads almost simultaneously along the entire length of the axon. The contraction signal reaches the muscle in a split second. An indicator such as the critical level of membrane depolarization means the point at which the peak action potential is achieved. After muscle contraction along the entire axon, repolarization begins.
Molecular mechanisms of action potential generation
The active properties of the membrane that ensure the occurrence of an action potential, based mainly on the behavior of voltage-gated sodium (Na +) and potassium (K +) channels. The initial phase of AP is formed by the input sodium current, later potassium channels open and the output K + -current returns the membrane potential to the initial level. The initial ion concentration is then restored by the sodium-potassium pump.
During the PD, channels pass from state to state: in Na + channels there are three main states - closed, open and inactivated (in reality everything is more complicated, but these three states are enough for description), in K + channels there are two - closed and open.
The behavior of the channels involved in the formation of PD is described in terms of conductivity and calculated through transfer coefficients.
Carryover coefficients were derived by Alan Lloyd Hodgkin and Andrew Huxley.
Conductivity for potassium GK per unit area
| , |
| Where: |
| an — Transfer coefficient from closed to open state for K+ channels [1/s]; |
| bn — Transfer coefficient from open to closed state for K+ channels [1/s]; |
| n — Fraction of K+ channels in the open state; |
| (1 - n) - Fraction of K + channels in the closed state |
The conductivity for sodium G Na per unit area
is more difficult to calculate, since, as already mentioned, in voltage-dependent Na + channels, in addition to the closed / open states, the transition between which is a parameter, there are also inactivated / not inactivated states, the transition between which is described through a parameter
| , | , |
| Where: | Where: |
| am — Transfer coefficient from closed to open state for Na + channels [1/s]; | ah — Transfer coefficient from inactivated to non-inactivated state for Na + channels [1/s]; |
| bm — Transfer coefficient from open to closed state for Na + channels [1 / s]; | bh — Transfer coefficient from non-inactivated to inactivated state for Na + channels [1 / s]; |
| m — Fraction of Na + channels in the open state; | h — Fraction of Na + channels in a non-inactivated state; |
| (1 - m) - Fraction of Na + channels in the closed state | (1 - h) - Fraction of Na + channels in the inactivated state. |
Story
The main provisions of the membrane theory of excitation were formulated by the German neurophysiologist Yu. Bernstein
In 1902, Julius Bernstein put forward a hypothesis according to which the cell membrane allows K+ ions into the cell, and they accumulate in the cytoplasm. The calculation of the resting potential value using the Nernst equation for the potassium electrode satisfactorily coincided with the measured potential between the muscle sarcoplasm and the environment, which was about -70 mV. According to the theory of Yu. Bernstein, when a cell is excited, its membrane is damaged, and K + ions leave the cell along a concentration gradient until the membrane potential becomes zero. The membrane then restores its integrity and the potential returns to the resting potential level.
This model was developed in their 1952 work by Alan Lloyd Hodgkin and Andrew Huxley, in which they described the electrical mechanisms responsible for the generation and transmission of a nerve signal in the squid giant axon. For this, the authors of the model received the Nobel Prize in Physiology or Medicine for 1963. The model is called the Hodgkin-Huxley model
In 2005, Thomas Heimburg and Andrew D. Jackson proposed the soliton model, based on the assumption that the signal propagates through neurons in the form of solitons - stable waves propagating along the cell membrane.
Anatomy of the conduction system
Conduction system of the heart
Quite often, not only the medical worker, but also the patient who comes for an appointment, hears the phrase “repolarization processes.” What is this in essence? Sometimes a lack of knowledge forces the patient to think a lot, and the fruits of reflection lead him to unreasonable worries and sorrows. And all because there is a lack of understanding of the simple truths of electrophysiology. So, our heart, having a conducting system, has the ability to be excited and return to a state of rest. This definition is, of course, conditional. After all, this organ works 24 hours a day, which means that there should be no pauses in the work of a healthy heart.
Let us turn specifically to its electrophysiology. “From head to toe,” our heart is provided with a conducting system, which is represented by nodes, bundles and fibers. The structural unit of this system is the atypical muscle cell. It contains fewer contractile elements of myofibrils, but more sarcoplasm - cytoplasm that fills the space between myofibrils. It is the sarcoplasm that ensures the conduction of exciting impulses inside the fiber. Even externally, these pathways can be distinguished with the naked eye - they are a little paler.
The effect of certain substances on the action potential
Some substances of organic or synthetic origin can block the formation or passage of PD:
- Batrachotoxin has been found in some representatives of the leaf climber genus. Sustainably and irreversibly increases the permeability of membranes to sodium ions.
- Poneratoxin was found in ants of the genus Paraponera. Blocks sodium channels.
- Tetrodotoxin was found in the tissues of fish of the Skelezubovi family, from which the Japanese delicacy Fugu is prepared. Blocks sodium channels.
- The mechanism of action of most anesthetics (Procaine, Lidocaine) is based on blocking sodium channels and, accordingly, blocking the conduction of impulses along sensitive nerve fibers.
- 4-Aminopyridine - reversely blocks potassium channels, prolongs the duration of the action potential. Can be used in the treatment of multiple sclerosis.
- ADWX 1 - reversely blocks potassium channels. Under experimental conditions, it alleviated the course of acute disseminated encephalomyelitis in rats.
