Heart- a muscular organ consisting of four chambers:
- the right atrium, which collects venous blood from the body;
- the right ventricle, which pumps venous blood into the pulmonary circulation - into the lungs, where gas exchange with atmospheric air occurs;
- the left atrium, which collects oxygenated blood from the pulmonary veins;
- the left ventricle, which ensures the movement of blood to all organs of the body.
Cardiomyocytes
The walls of the atria and ventricles consist of striated muscle tissue, represented by cardiomyocytes and having a number of differences from skeletal muscle tissue. Cardiomyocytes make up about 25% of total number heart cells and about 70% of the myocardial mass. The walls of the heart contain fibroblasts, vascular smooth muscle cells, endothelial and nerve cells.
The membrane of cardiomyocytes contains proteins that perform transport, enzymatic and receptor functions. Among the latter are receptors for hormones, catecholamines and other signaling molecules. Cardiomyocytes have one or more nuclei, many ribosomes and a Golgi apparatus. They are capable of synthesizing contractile and protein molecules. These cells synthesize some proteins specific to certain stages of the cell cycle. However, cardiomyocytes early lose the ability to divide and their maturation, as well as adaptation to increasing loads, is accompanied by an increase in cell mass and size. The reasons why cells lose their ability to divide remain unclear.
Cardiomyocytes differ in their structure, properties and functions. There are typical, or contractile, cardiomyocytes and atypical ones, which form the conduction system in the heart.
Typical cardiomyocytes - contractile cells that form the atria and ventricles.
Atypical cardiomyocytes - cells of the conduction system of the heart, ensuring the occurrence of excitation in the heart and its conduction from the site of origin to the contractile elements of the atria and ventricles.
The vast majority of cardiomyocytes (fibers) of the heart muscle belong to the working myocardium, which provides. Myocardial contraction is called relaxation - . There are also atypical cardiomyocytes and heart fibers, the function of which is to generate excitation and conduct it to the contractile myocardium of the atria and ventricles. These cells and fibers form conduction system of the heart.
Heart surrounded pericardium- pericardial sac that separates the heart from neighboring organs. The pericardium consists of a fibrous layer and two layers of serous pericardium. The visceral layer, called epicardium, is fused with the surface of the heart, and the parietal one is fused with the fibrous layer of the pericardium. The gap between these layers is filled with serous fluid, the presence of which reduces the friction of the heart with surrounding structures. The relatively dense outer layer of the pericardium protects the heart from overstretching and excessive blood filling. The inner surface of the heart is represented by an endothelial lining called endocardium. Located between the endocardium and pericardium myocardium - contractile fibers of the heart.
A set of atypical cardiomyocytes forming nodes: sinoatrial and atrioventricular, internodal tracts of Bachmann, Wenckebach and Thorel, bundles of His and Purkinje fibers.
The functions of the conduction system of the heart are the generation of an action potential, its conduction to the contractile myocardium, the initiation of contraction and the provision of a certain supply to the atria and ventricles. The emergence of excitation in the pacemaker is carried out with a certain rhythm arbitrarily, without the influence of external stimuli. This property of pacemaker cells is called .
The conduction system of the heart consists of nodes, bundles and fibers formed by atypical muscle cells. Its structure includes sinoatrial(SA) knot, located in the wall of the right atrium in front of the mouth of the superior vena cava (Fig. 1).
Rice. 1. Schematic structure of the conduction system of the heart
Bundles of atypical fibers (Bachmann, Wenckebach, Thorel) depart from the SA node. The transverse bundle (Bachmann) conducts excitation to the myocardium of the right and left atria, and the longitudinal ones - to atrioventricular(AB) knot, located under the endocardium of the right atrium in its lower corner in the area adjacent to the interatrial and atrioventricular septa. Departs from the AV node Gps beam. It conducts excitation to the ventricular myocardium and since at the border of the atria and ventricles myocardium there is a connective tissue septum formed by dense fibrous fibers, then healthy person The His bundle is the only pathway through which an action potential can propagate to the ventricles.
The initial part (trunk of the His bundle) is located in the membranous part of the interventricular septum and is divided into the right and left bundle branches, which are also located in the interventricular septum. The left bundle branch is divided into anterior and posterior branches, which, like the right bundle branch, branch and end in Purkinje fibers. Purkinje fibers are located in the subendocardial region of the heart and conduct action potentials directly to the contractile myocardium.
Automation mechanism and excitation through the conductive system
The generation of action potentials is carried out under normal conditions by specialized cells of the SA node, which is called the 1st order pacemaker or pacemaker. In a healthy adult, action potentials are rhythmically generated in it with a frequency of 60-80 per 1 minute. The source of these potentials are atypical round cells of the SA node, which are small in size, contain few organelles and a reduced contractile apparatus. They are sometimes called P cells. The node also contains elongated cells that occupy an intermediate position between atypical and normal contractile atrial cardiomyocytes. They are called transitional cells.
β-cells are coated with a number of diverse ion channels. Among them there are passive and voltage-gated ion channels. The resting potential in these cells is 40-60 mV and is unstable, due to the different permeability of the ion channels. During cardiac diastole, the cell membrane spontaneously slowly depolarizes. This process is calledslow diastolic depolarization(MDD) (Fig. 2).
Rice. 2. Action potentials of contractile myocardial myocytes (a) and atypical cells of the SA node (b) and their ionic currents. Explanations in the text
As can be seen in Fig. 2, immediately after the end of the previous action potential, spontaneous DMD of the cell membrane begins. DMD at the very beginning of its development is caused by the entry of Na+ ions through passive sodium channels and a delay in the exit of K+ ions due to the closure of passive potassium channels and a decrease in the exit of K+ ions from the cell. Let us remember that K ions escaping through these channels usually provide repolarization and even some degree of hyperpolarization of the membrane. It is obvious that a decrease in the permeability of potassium channels and a delay in the release of K+ ions from the P-cell, together with the entry of Na+ ions into the cell, will lead to the accumulation of positive charges on the inner surface of the membrane and the development of DMD. DMD in the range of Ecr values (about -40 mV) is accompanied by the opening of voltage-dependent slow calcium channels through which Ca 2+ ions enter the cell, causing the development of the late part of DMD and the zero phase of the action potential. Although it is assumed that at this time additional entry of Na+ ions into the cell through calcium channels (calcium-sodium channels) is possible, the decisive role in the development of the self-accelerating phase of depolarization and membrane recharging is played by Ca 2+ ions entering the pacemaker cell. The generation of an action potential develops relatively slowly, since the entry of Ca 2+ and Na+ ions into the cell occurs through slow ion channels.
Recharging of the membrane leads to inactivation of calcium and sodium channels and cessation of ion entry into the cell. By this time, the release of K+ ions from the cell through slow voltage-dependent potassium channels increases, the opening of which occurs at Ecr simultaneously with the activation of the mentioned calcium and sodium channels. The escaping K+ ions repolarize and somewhat hyperpolarize the membrane, after which their exit from the cell is delayed and thus the process of self-excitation of the cell is repeated. Ionic balance in the cell is maintained by the work of the sodium-potassium pump and the sodium-calcium exchange mechanism. The frequency of action potentials in the pacemaker depends on the rate of spontaneous depolarization. As this speed increases, the frequency of generation of pacemaker potentials and the heart rate increase.
From the SA node, the potential propagates at a speed of about 1 m/s in the radial direction to the myocardium of the right atrium and along specialized pathways to the myocardium of the left atrium and to the AV node. The latter is formed by the same types of cells as the SA node. They also have the ability to self-excite, but this does not occur under normal conditions. AV node cells can begin to generate action potentials and become the pacemaker of the heart when they are not receiving action potentials from the SA node. Under normal conditions, action potentials originating in the SA node are conducted through the AV node region to the fibers of the His bundle. The speed of their conduction in the area of the AV node decreases sharply and the time period required for the propagation of the action potential extends to 0.05 s. This temporary delay in the conduction of the action potential in the region of the AV node is called atrioventricular delay.
One of the reasons for AV delay is the peculiarity of ion and, above all, calcium ion channels in the membranes of the cells that form the AV node. This is reflected in the lower rate of DMD and action potential generation by these cells. In addition, the cells of the intermediate region of the AV node are characterized by a longer refractory period, longer than the repolarization phase of the action potential. The conduction of excitation in the area of the AV node presupposes its occurrence and transmission from cell to cell, therefore, the slowing down of these processes on each cell involved in the conduction of the action potential causes a longer total time for the conduction of the potential through the AV node.
AV delay has important physiological significance in establishing a specific sequence of atria and ventricles. Under normal conditions, atrial systole always precedes ventricular systole, and ventricular systole begins immediately after the completion of atrial systole. It is thanks to the AV delay in the conduction of the action potential and the later excitation of the ventricular myocardium in relation to the atrial myocardium that the ventricles are filled with the required volume of blood, and the atria have time to complete systole (prsystole) and expel an additional volume of blood into the ventricles. The volume of blood in the cavities of the ventricles, accumulated at the beginning of their systole, contributes to the most effective contraction of the ventricles.
In conditions where the function of the SA node is impaired or there is a blockade of the conduction of the action potential from the SA node to the AV node, the AV node can take on the role of cardiac pacemaker. Obviously, due to the lower speeds of DMD and the development of the action potential of the cells of this node, the frequency of action potentials generated by it will be lower (about 40-50 per 1 min) than the frequency of potential generation by the cells of the C A node.
The time from the moment of cessation of action potentials from the pacemaker to the AV node until the moment of its manifestation is called pre-automatic pause. Its duration is usually in the range of 5-20 s. At this time, the heart does not contract and the shorter the pre-automatic pause, the better for the sick person.
If the function of the SA and AV nodes is impaired, the His bundle may become the pacemaker. In this case, the maximum frequency of its excitations will be 30-40 per minute. At this heart rate, even at rest, a person will experience symptoms of circulatory failure. Purkinje fibers can generate up to 20 impulses per minute. From the above data it is clear that in the conduction system of the heart there is car gradient- a gradual decrease in the frequency of generation of action potentials by its structures in the direction from the SA node to the Purkinje fibers.
Having overcome the AV node, the action potential spreads to the His bundle, then to the right bundle branch, the left bundle branch and its branches and reaches the Purkinje fibers, where its conduction speed increases to 1-4 m/s and in 0.12-0.2 c the action potential reaches the endings of the Purkinje fibers, with the help of which the conduction system interacts with the cells of the contractile myocardium.
Purkinje fibers are formed by cells having a diameter of 70-80 microns. It is believed that this is one of the reasons that the speed of the action potential in these cells reaches the highest values - 4 m/s compared to the speed in any other myocardial cells. The time of excitation along the conduction system fibers connecting the SA and AV nodes, the AV node, the His bundle, its branches and Purkinje fibers to the ventricular myocardium determines the duration of the PO interval on the ECG and normally ranges from 0.12-0.2 With.
It is possible that transitional cells, characterized as intermediate between Purkinje cells and contractile cardiomyocytes, in structure and properties, take part in the transfer of excitation from Purkinje fibers to contractile cardiomyocytes.
In skeletal muscle, each cell receives an action potential along the axon of the motor neuron and, after synaptic signal transmission, its own action potential is generated on the membrane of each myocyte. The interaction between Purkinje fibers and the myocardium is completely different. All Purkinje fibers carry an action potential to the myocardium of the atria and both ventricles that arises from one source—the pacemaker of the heart. This potential is conducted to the points of contact between the endings of fibers and contractile cardiomyocytes in the subendocardial surface of the myocardium, but not to each myocyte. There are no synapses or neurotransmitters between Purkinje fibers and cardiomyocytes, and excitation can be transmitted from the conduction system to the myocardium through gap junction ion channels.
The potential arising in response on the membranes of some contractile cardiomyocytes is conducted along the surface of the membranes and along the T-tubules into the myocytes using local circular currents. The potential is also transmitted to neighboring myocardial cells through the channels of the gap junctions of the intercalary discs. The speed of action potential transmission between myocytes reaches 0.3-1 m/s in the ventricular myocardium, which contributes to the synchronization of cardiomyocyte contraction and more efficient myocardial contraction. Impaired transmission of potentials through ion channels of gap junctions may be one of the reasons for desynchronization of myocardial contraction and the development of weakness of its contraction.
In accordance with the structure of the conduction system, the action potential initially reaches the apical region of the interventricular septum, papillary muscles, and the apex of the myocardium. The excitation that arose in response to the arrival of this potential in the cells of the contractile myocardium spreads in directions from the apex of the myocardium to its base and from the endocardial surface to the epicardial.
Functions of the conduction system
Spontaneous generation of rhythmic impulses is the result of the coordinated activity of many cells of the sinoatrial node, which is ensured by close contacts (nexuses) and electrotonic interaction of these cells. Having arisen in the sinoatrial node, excitation spreads through the conduction system to the contractile myocardium.
Excitation spreads through the atria at a speed of 1 m/s, reaching the atrioventricular node. In the heart of warm-blooded animals, there are special pathways between the sinoatrial and atrioventricular nodes, as well as between the right and left atria. The speed of excitation propagation in these pathways is not much higher than the speed of excitation propagation throughout the working myocardium. In the atrioventricular node, due to the small thickness of its muscle fibers and the special way they are connected (built on the principle of a synapse), a certain delay in the conduction of excitation occurs (the propagation speed is 0.2 m/s). Due to the delay, excitation reaches the atrioventricular node and Purkinje fibers only after the atrial muscles have time to contract and pump blood from the atria to the ventricles.
Hence, atrioventricular delay provides the necessary sequence (coordination) of contractions of the atria and ventricles.
The speed of propagation of excitation in the His bundle and in Purkinje fibers reaches 4.5-5 m/s, which is 5 times greater than the speed of propagation of excitation throughout the working myocardium. Due to this, the cells of the ventricular myocardium are involved in contraction almost simultaneously, i.e. synchronously. The synchronicity of cell contraction increases the power of the myocardium and the efficiency of the pumping function of the ventricles. If excitation were carried out not through the atrioventricular bundle, but through the cells of the working myocardium, i.e. diffusely, then the period of asynchronous contraction would last much longer, the myocardial cells would not be involved in contraction simultaneously, but gradually, and the ventricles would lose up to 50% of their power. This would not create enough pressure to allow blood to be released into the aorta.
Thus, the presence of a conduction system provides a number of important physiological features of the heart:
- spontaneous depolarization;
- rhythmic generation of impulses (action potentials);
- the necessary sequence (coordination) of contractions of the atria and ventricles;
- synchronous involvement of ventricular myocardial cells in the process of contraction (which increases the efficiency of systole).
October 26, 2017 No comments
According to the traditional view, the reason for the occurrence of cell potentials both at rest and during their activation is primarily the uneven distribution of potassium and sodium ions between the contents of the cells and the extracellular environment. Let us recall that the concentration of potassium ions inside cells is 20-40 times higher than their content in surrounding the cell liquid (note that the excess of positive charges of potassium ions inside the cells is compensated mainly by anions of organic acids), and the sodium concentration in the intercellular fluid is 10-20 times higher than inside the cells.
This uneven distribution of ions is ensured by the activity of the “sodium-potassium pump”, i.e. N a+/K+-ATPase. The occurrence of the resting potential is mainly due to the presence of a concentration gradient of potassium ions. This point of view is justified by the fact that potassium ions inside the cell are predominantly in a free state, i.e. are not associated with other ions or molecules, so they can diffuse freely.
According to the well-known theory of Hodgkin et al., the cell membrane at rest is mainly permeable only to potassium ions. Potassium ions diffuse along a concentration gradient through the cell membrane into the environment, while anions cannot penetrate the membrane and remain on its inner side.
Due to the fact that potassium ions have a positive charge, and the anions remaining on the inner surface of the membrane have a negative charge, the outer surface of the membrane is charged positively, and the inner - negatively. It is clear that diffusion continues only until an equilibrium is established between the forces of the emerging electric field and diffusion forces.
The membrane at rest is permeable not only to potassium ions, but also to a small extent to sodium and chlorine ions. The cell membrane potential is the net electromotive force generated by these three diffusion channels. The penetration of sodium from the surrounding fluid into the cell along the concentration gradient leads to a slight decrease membrane potential, and then to their depolarization, i.e. a decrease in polarization (the inner surface of the membranes becomes positively charged again, and the outer surface becomes negatively charged). Depolarization underlies the formation of membrane action potentials.
All cells of excitable tissues, when exposed to various stimuli of sufficient strength, are capable of entering a state of excitation. Excitability is the ability of cells to quickly respond to stimulation, manifested through a combination of physical, physicochemical processes and functional changes.
An obligatory sign of excitation is a change in the electrical state of the cell membrane. In general, the permeability of the membrane increases (this is one of the general reactions of the cell to various damaging influences) for all ions. As a result, ionic gradients disappear and the potential difference across the membrane decreases to zero. This phenomenon of “removal” (cancellation) of polarization is called depolarization.
In this case, the inner surface of the membranes again becomes positively charged, and the outer surface becomes negatively charged. This redistribution of ions is temporary; after the end of excitation, the original resting potential is restored again. Depolarization underlies the formation of membrane action potentials.
When membrane depolarization reaches or exceeds a certain threshold level, the cell becomes excited, i.e., an action potential appears, which is an excitation wave moving across the membrane in the form of a short-term change in membrane potential in a small area of the excitable cell. The action potential has standard amplitude and time parameters that do not depend on the strength of the stimulus that caused it (the “all or nothing” rule). Action potentials ensure the conduction of excitation along nerve fibers and initiate the processes of contraction of muscle cells.
Action potentials arise as a result of excess diffusion of sodium ions from the surrounding fluid into the cell compared to rest. The period during which the permeability of the membrane for sodium ions increases when the cell is excited is very short-lived (0.5-1.0 ms); following this, an increase in the permeability of the membrane to potassium ions is observed and, consequently, an increase in the diffusion of these ions from the cell to the outside.
An increase in the potassium ion flux 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. Thus, the second stage of excitation 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 continues until the resting potential is restored. After this, the permeability to potassium ions also decreases 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 inner one. This process of returning the membrane potential to its original level, i.e. level of the resting potential is called repolarization.
The repolarization process is always longer than the depolarization process and is represented on the action potential curve (see below) as a flatter descending branch. Thus, membrane repolarization occurs not as a result of the reverse movement of sodium ions, but as a result of the release of an equivalent amount of potassium ions from the cell.
In some cases, the permeability of the membrane for sodium and potassium ions remains increased after the end of excitation. This leads to the fact that so-called trace potentials are recorded on the action potential curve, which are characterized by small amplitude and relatively long duration.
Under the influence of subthreshold stimuli, the permeability of the membrane to sodium increases slightly and depolarization does not reach a critical value. Depolarization of the membrane less than a critical level is called local potential, which can be represented as "electrotonic potential" or "local response".
Local potentials are not able to propagate over significant distances, but attenuate near the place of their origin. These potentials do not obey the “all or nothing” rule - their amplitude and duration are proportional to the intensity and duration of the irritating stimulus.
With repeated action of subthreshold stimuli, local potentials can be summed up, reach a critical value and cause the appearance of propagating action potentials. Thus, local potentials may precede the occurrence of action potentials. This is especially clearly observed in the cells of the conduction system of the heart, where slow diastolic depolarization, developing spontaneously, causes the appearance of action potentials.
It should be noted that the transmembrane movement of sodium and potassium ions is not the only mechanism for generating an action potential. Transmembrane diffusion currents of chlorine and calcium ions also take part in its formation.
The above general information Membrane potentials apply equally to both atypical cardiomyocytes that form the conduction system of the heart and contractile cardiomyocytes - the direct performers of the pumping function of the heart. Changes in membrane charge underlie the generation of electrical impulses - signals necessary to coordinate the functioning of contractile cardiomyocytes of the atria and ventricles throughout the cardiac cycle and the pumping function of the heart as a whole.
Specialized cells - “pacemakers” of the sinus node have the ability to spontaneously (without external influence) generate impulses, i.e. action potentials. This property, called automatism, is based on the process of slow diastolic depolarization, which consists of a gradual decrease in the membrane potential to a threshold (critical) level from which rapid depolarization of the membrane begins, i.e., phase 0 of the action potential.
Spontaneous diastolic depolarization is ensured by ionic mechanisms, among which the traditionally nonspecific current of Na+ ions into the cell occupies a special position. However, according to modern research, this current accounts for only about 20% of the activity of transmembrane ion movement.
Currently great importance has the so-called delayed (delayed) current of K+ ions leaving the cells. It has been established that inhibition (delay) of this current ensures up to 80% of the automaticity of pacemakers of the sinus node, and an increase in the K+ current slows down or completely stops pacemaker activity. A significant contribution to achieving the threshold potential is made by the current of Ca++ ions into the cell, the activation of which turned out to be necessary to achieve the threshold potential. In this regard, it is appropriate to pay attention to the fact that clinicians are well aware of how sensitive sinus rhythm is to blockers of Ca++ channels (L-type) of the cell membrane, for example, verapamil, or to beta-blockers, for example, propranolol , capable of influencing these channels through catecholamines.
In the aspect of electrophysiological analysis of the pumping function of the heart, the interval between systoles is equal to the period of time during which the resting membrane potential in the cells of the sinus node shifts to the level of the threshold excitation potential.
Three mechanisms influence the duration of this interval and therefore the heart rate. The first and most important of them is the rate (slope of rise) of diastolic depolarization. As it increases, the threshold excitation potential is reached faster, which determines the increase in sinus rhythm. The opposite change, i.e., a slowdown in spontaneous diastolic depolarization, leads to a slowdown in sinus rhythm.
The second mechanism that influences the level of automatism of the sinus node is a change in the resting membrane potential of its cells (maximum diastolic potential). When this potential increases (in absolute values), i.e., when the cell membrane is hyperpolarized (for example, under the influence of acetylcholine), it takes more time to reach the threshold excitation potential, unless, of course, the rate of diastolic depolarization remains unchanged. The consequence of this shift will be a decrease in the number of heartbeats per unit time.
The third mechanism is changes in the threshold excitation potential, the shift of which towards zero lengthens the path of diastolic depolarization and contributes to a slowdown in sinus rhythm. The approach of the threshold potential to the resting potential is accompanied by an increase in sinus rhythm. Various combinations of the three main electrophysiological mechanisms regulating the automatism of the sinus node are also possible.
Phases and main ionic mechanisms of the formation of the transmembrane action potential
The following phases of TMPD are distinguished:
Phase 0 - depolarization phase; characterized by rapid (within 0.01 s) recharging of the cell membrane: its inner surface becomes positively charged, and its outer surface becomes negatively charged.
Phase 1 is the phase of initial rapid repolarization; manifested by a small initial decrease in TMPD from +20 to 0 mV or slightly lower.
Phase 2 - plateau phase; a relatively long period (about 0.2 s), during which the TMPD value is maintained at the same level
Phase 3 - phase of final rapid repolarization; During this period, the original polarization of the membrane is restored: its outer surface becomes positively charged, and its inner surface becomes negatively charged (-90 mV).
Phase 4 - diastole phase; the TMPD value of the contractile cell is maintained at approximately -90 mV, and restoration (not without the participation of Na+/K+-Hacoca) of the original transmembrane gradients of K+, Na+, Ca2+ and SG ions occurs.
Different phases of TMPD are characterized by unequal excitability of the muscle fiber.
At the beginning of TMPD (phases 0,1,2), cells are completely non-excitable (absolute refractory period). During rapid terminal repolarization (phase 3), excitability is partially restored (relative refractory period). During diastole (phase 4), there is no refractoriness and the myocardial fiber completely restores its excitability. Changes in cardiomyocyte excitability during formation transmembrane potential actions are reflected on the ECG complex.
Myocardial cells at rest are characterized by low permeability to Na+, therefore spontaneous shifts in membrane potential are not observed in them.
Cell action potential the working myocardium consists of a phase of fast depolarization, an initial fast repolarization, which turns into a phase of slow repolarization (plateau phase), and a phase of fast final repolarization (Fig. 9.8). The rapid depolarization phase is created by a sharp increase in the permeability of the membrane to sodium ions, which leads to a rapid inward sodium current. The sign of the membrane potential changes from -90 to +30 mV. Membrane depolarization causes activation of slow sodium-calcium channels, resulting in an additional depolarizing inward calcium current that leads to a plateau phase. Sodium channels are inactivated and the cells are completely refractory. Terminal repolarization in myocardial cells is due to a gradual decrease in membrane permeability to calcium and an increase in permeability to potassium. As a result, the incoming calcium current decreases and the outgoing potassium current increases, which ensures rapid restoration of the resting membrane potential. The duration of the action potential of cardiomyocytes is 300-400 ms, which corresponds to the duration of myocardial contraction. The resting potential is maintained at -90 mV and is determined by K+ ions.
Features of excitability and contractility of the myocardium.
From the materials of last semester, you remember that excitability is the ability of excitable tissue under the influence of a stimulus to move from a state of rest to a state of excitation. Excitement in excitable tissues manifests itself in the form of bioelectric processes and a specific response. In the contractile cells of the myocardium, the action potential has its own characteristics. A feature of the action potential of contractile myocardium is the presence of a long phase of slow repolarization, which is caused by the incoming current of Ca ++ ions. This leads to the fact that the duration of the action potential of cardiomyocytes reaches 250-300 ms. Let me remind you that the duration of the action potential of muscle fibers of skeletal muscles is about 5 ms. There are certain relationships between the action potential curve, the curve of changes in excitability and the curve reflecting changes in the length of the muscle fiber. Unlike skeletal muscle, in which the action potential is realized during the latent period, in the contractile myocardium the action potential coincides in time with the duration of systole and for the most part diastole. Since the duration of the high-voltage peak coincides with the duration of the absolute refractory phase, the heart during systole and during 2/3 of diastole cannot respond with additional excitation to any influences. In addition, in the final part of diastole, myocardial excitability is significantly reduced. Therefore, the myocardium, unlike skeletal muscle, is not capable of tetanic contraction. This feature of the myocardium was formed during evolutionary development as an adaptive feature, since the main function of the heart is that of a biological pump. This function can be performed efficiently only under conditions of rhythmic single myocardial contractions.
Thus, we see that two properties of the myocardium, excitability and contractility, are interconnected and determine the important functions of the heart.
Extrasystoles are contractions of the heart muscle that are extraordinary in relation to the normal heart rhythm. Usually, extrasystoles are felt by the patient as a strong cardiac impulse with a dip or fading after it. When palpating the pulse at this time, there may be a loss of the pulse wave. Some extrasystoles may occur unnoticed by the patient.
Extrasystole occurs when an electrical impulse occurs outside the sinus node. Such an impulse spreads through the heart muscle in the period between normal impulses and causes an extraordinary contraction of the heart. The source of excitation, in which an extraordinary impulse occurs, can appear anywhere in the conduction system of the heart. The formation of such a lesion is caused by both diseases of the heart itself (cardiosclerosis, myocardial infarction, inflammatory diseases of the heart muscle, heart defects) and diseases of other organs.
At rest, the inner surface of the cardiomyocyte membranes is negatively charged. The appearance of the membrane potential of cardiomyocytes is due to selective permeability of their membrane for potassium ions. Its value in contractile cardiomyocytes is 80-90 mV They distinguish the following phases:
1. Depolarization phase(by opening sodium and calcium channels of the membrane through which these ions enter the cytoplasm);
2. Rapid initial repolarization phase(fast inactivation of sodium channels, and slow inactivation of calcium channels. At the same time, potassium channels are activated)
3. Delayed repolarization phase
4. Rapid terminal repolarization phase
The duration of cardiomyocyte AP is 200-400 ms.
The action potential of cardiomyocytes of the His-Purkinje system and working ventricular myocardium is distinguished five phases:
*Rapid depolarization phase ( phase 0) is caused by the entry of Na+ ions through the so-called fast sodium channels.
*Then, after a short phase of early rapid repolarization ( phase 1),
*a phase of slow depolarization, or plateau, begins ( phase 2). It is caused by the simultaneous entry of Ca2+ ions through slow calcium channels and the release of K+ ions.
*Late rapid repolarization phase ( phase 3) is due to the predominant release of K+ ions.
*Finally, phase 4- this is the resting potential.
The ability of some heart cells to spontaneously produce action potentials is called automaticity. This ability is possessed by the cells of the sinus node, atrial conduction system, AV node and the His-Purkinje system.
Potential dependent ion channels: sodium and calcium channels(consist of main a-subunits With 4 transmembrane subunits, each consists of 624 spirals, twisted together and form one functioning pore of each calcium channel) and some of the potassium channels (simply arranged).
Activation at the molecular level is a change in the charge of the 4th transmembrane segment - a polarization sensor, of each of the 4 subunits of the sodium or calcium channel. The a-subunit enhances the flow of calcium through the pores. Channels vary from completely closed to completely open
Action potentials (AP), recorded in different parts of the heart using intracellular microelectrodes,
Refractory period- a period of time after the occurrence of an action potential on the excitable membrane, during which the excitability of the membrane decreases and then gradually recovers to its original level.
The refractory period is due to the peculiarities of the behavior of voltage-dependent sodium and voltage-dependent potassium channels of the excitable membrane.
During AP, voltage-gated sodium (Na+) and potassium (K+) channels switch from state to state. U Na+ channels ground states three - closed, open and inactivated. U K+ channels two main states - closed and open.
When the membrane is depolarized during AP, Na+ channels, after an open state, temporarily go into an inactivated state, and K+ channels open and remain open for some time after the end of AP, creating an outgoing K+ current that brings the membrane potential to the initial level.
As a result of inactivation of Na+ channels, an absolute refractory period occurs. Later, when some of the Na+ channels have already left the inactivated state, AP may occur.
25 . Postsynaptic potential (PSP) is a temporary change in the potential of the postsynaptic membrane in response to a signal received from the presynaptic neuron.
There are:
*excitatory postsynaptic potential (EPSP), which ensures depolarization of the postsynaptic membrane, and
*inhibitory postsynaptic potential (IPSP), providing hyperpolarization of the postsynaptic membrane.
Conventionally, the probability of triggering an action potential can be described as resting potential + sum of all excitatory postsynaptic potentials - sum of all inhibitory postsynaptic potentials > threshold for triggering an action potential.
Individual PSPs are usually small in amplitude and do not cause action potentials in the postsynaptic cell; however, unlike action potentials, they are gradual and can be summed up. There are two options for summation:
*temporary- combining signals arriving through one channel (when a new pulse arrives before the previous one fades);
*spatial- overlap of EPSPs of neighboring synapses;
The mechanism of occurrence of PSP. When an action potential arrives at the presynaptic terminal of a neuron, the presynaptic membrane depolarizes and voltage-gated calcium channels are activated. Calcium begins to enter the presynaptic terminal and causes exocytosis of vesicles filled with neurotransmitter. The neurotransmitter is released into the synaptic cleft and diffuses to the postsynaptic membrane. On the surface of the postsynaptic membrane, the transmitter binds to specific protein receptors (ligand-gated ion channels) and causes them to open.
26. Reduction- this is a change in the mechanical state of the myofibrillar apparatus of muscle fibers under the influence of nerve impulses. In 1939, Engelhardt and Lyubimova found that myosin has the properties of the enzyme adenosine triphosphatase, which breaks down ATP. It was soon established that when actin interacts with myosin, a complex is formed - actomyosin, the enzymatic activity of which is almost 10 times higher than that of myosin. During this period, development begins modern theory muscle contraction, which is called theory of sliding threads. According to this “sliding” theory, contraction is based on the interaction between actin and myosin filaments of myofibrils due to the formation of cross bridges between them.
During gliding, the actin and myosin filaments themselves do not shorten, but the length of the sarcomere (the basic contractile unit of striated muscles, which is a complex of several proteins consisting of three different fiber systems) changes. In a relaxed, and even more so stretched, muscle, the active filaments are located further from the center of the sarcomere, and the sarcomere is longer. During isotonic muscle contraction, actin filaments slide towards the center of the sarcomere along myosin filaments. The actin filaments are attached to the Z-membrane, pulling it along with them, and the sarcomere is shortened. The total shortening of all sarcomeres causes shortening of myofibrils, and the muscle contracts.
The following model of actin filament sliding is currently accepted.
The excitation impulse along the motor neuron reaches the neuromuscular synapse - the end plate, where acetylcholine is released, which interacts with the postsynaptic membrane, and an action potential arises in the muscle fiber, i.e. excitation of the muscle fiber occurs.
When Ca++ ions bind to troponin (the spherical molecules of which “sit” on actin chains), the latter is deformed, pushing tropomyosin into the grooves between the two actin chains. In this case, the interaction of actin with myosin heads becomes possible and contractile force occurs. The myosin heads make “rowing” movements and move the actin filament towards the center of the sarcomere.
Myosin filaments have many heads; they pull the actin filament with a combined, total force. With the same stroke movement of the heads, the sarcomere is shortened by approximately 1% of its length (and with an isotonic contraction, the muscle sarcomere can be shortened by 50% of its length in tenths of a second), therefore, the transverse bridges must perform approximately 50 “row” movements in the same period of time.
The cumulative shortening of successive sarcomeres of myofibrils leads to a noticeable muscle contraction. At the same time, ATP hydrolysis occurs. After the end of the action potential peak, the calcium pump (Ca-dependent ATPase) of the sarcoplasmic reticulum membrane is activated. Due to the energy released during the breakdown of ATP, the calcium pump pumps Ca ++ ions back into the cisterns of the sarcoplasmic reticulum, where Ca ++ is bound by a protein calsequestrin.
The concentration of Ca ++ ions in the muscle cytoplasm decreases to 10 - 8 m, and in the sarcoplasmic reticulum increases to 10 -3 m.
A decrease in the level of Ca ++ in the sarcoplasm suppresses the ATPase activity of actomyosin; in this case, the myosin cross bridges are disconnected from actin. Relaxation and lengthening of muscles occurs as a result of passive movement (without energy expenditure).
Thus, muscle contraction and relaxation is a series of processes unfolding in the following sequence: nerve impulse - release of acetylcholine by the presynaptic membrane of the neuromuscular synapse - interaction of acetylcholine with the postsynaptic membrane of the synapse - occurrence of an action potential - electromechanical coupling (conduction of excitation through T-tubules, release of Ca ++ and its effect on the troponin-tropomyosin-actin system) - formation of cross bridges and “sliding” of actin filaments along myosin filaments - decrease in the concentration of Ca ++ ions due to the work of the calcium pump - spatial change in the proteins of the contractile system - relaxation of myofibrils.
After death, the muscles remain tense, the so-called rigor mortis, since the cross-links between actin and myosin filaments cannot be broken due to the lack of ATP energy and the impossibility of the calcium pump.
27. Mechanism of conduction of excitation along unmyelinated nerve fibers. At rest, the entire inner surface of the nerve fiber membrane carries a negative charge, and the outer side of the membrane carries a positive charge. Electric current does not flow between the inner and outer sides of the membrane, since the lipid layer of the membrane has high electrical resistance. During the development of an action potential, charge reversal occurs in the excited region of the membrane. An electric current begins to flow at the boundary of the excited and unexcited areas. The electric current irritates the nearest section of the membrane and brings it into a state of excitation, while the previously excited areas return to a state of rest. Thus, the wave of excitation covers all new areas of the nerve fiber membrane.
IN myelinated in the nerve fiber, areas of the membrane covered with the myelin sheath are inexcitable; excitation can occur only in areas of the membrane located in the area of nodes of Ranvier. When an action potential develops in one of the nodes of Ranvier, a reversal of the membrane charge occurs. Between the electronegative and electropositive sections of the membrane occurs electricity, which irritates neighboring areas of the membrane. However, only a section of the membrane in the area of the next node of Ranvier can go into a state of excitation. Thus, excitation spreads across the membrane in leaps and bounds from one node of Ranvier to another.
28. Action potential is an excitation wave moving across the membrane of a living cell during the transmission of a nerve signal. In essence, it is an electrical discharge - a rapid short-term change in potential in a small area of the membrane of an excitable cell (neuron, muscle fiber or glandular cell), 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 neighboring areas of the membrane. The action potential is the physical basis of a nerve or muscle impulse that plays a signaling (regulatory) role.
Action potentials can vary in their parameters depending on the type of cell and even on different parts of the membrane of the same cell. Most typical example differences: the action potential of the heart muscle and the action potential of most neurons. However, the basis of any action potential is the following phenomena:
The membrane of a living cell is polarized - its inner surface is negatively charged in relation to the outer surface due to the fact that in the solution near its outer surface there is a larger number of positively charged particles (cations), and near the inner surface there is a larger number of negatively charged particles (anions ).
The membrane has selective permeability - its permeability for various particles (atoms or molecules) depends on their sizes, electric charge and chemical properties.
The membrane of an excitable cell is capable of quickly changing its permeability to 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.
Action potential phases
Prespike- the process of slow depolarization of the membrane to a critical level of depolarization (local excitation, local response).
Peak Potential, or spike, consisting of an ascending part (membrane depolarization) and a descending part (membrane repolarization).
Negative trace potential- from the critical level of depolarization to the initial level of membrane polarization (trace depolarization).
Positive trace potential- an increase in membrane potential and its gradual return to its original value (trace hyperpolarization).
Ion channels are pore-forming proteins (single or entire complexes) that maintain the potential difference that exists between the outer and inner sides of the cell membrane of all living cells. They belong to transport proteins. With their help, ions move according to their electrochemical gradients through the membrane. Such complexes are a collection of identical or homologous proteins tightly packed in the lipid bilayer of the membrane around an aqueous pore. The channels are located in the plasmalemma and some internal cell membranes.
The ions passing through ion channels are Na+ (sodium), K+ (potassium), Cl− (chlorine), and Ca++ (calcium). Due to the opening and closing of ion channels, the concentration of ions on different sides of the membrane changes and a shift in the membrane potential occurs.
Channel proteins consist of subunits that form a structure with a complex spatial configuration, in which, in addition to the pore, there are usually molecular systems of opening, closing, selectivity, inactivation, reception and regulation. Ion channels can have several sites (sites) for binding to control molecules.
29. Myogenic regulation. A study of the dependence of the force of heart contractions on the stretching of its chambers showed that the force of each cardiac contraction depends on the magnitude of the venous inflow and is determined by the final diastolic length of the myocardial fibers. As a result, a rule was formulated that entered physiology as Starling’s law: “The force of contraction of the ventricles of the heart, measured by any method, is a function of the length of the muscle fibers before contraction.”
Inotropic effects on the heart due to the Frank-Starling effect can occur in various physiological conditions. They play a leading role in increasing cardiac activity during increased muscular work, when contracting skeletal muscles cause periodic compression of the veins of the extremities, which leads to an increase in venous inflow due to the mobilization of the reserve of blood deposited in them. Negative inotropic influences through this mechanism play a significant role in changes in blood circulation during the transition to a vertical position (orthostatic test). These mechanisms are of great importance for coordinating changes in cardiac output and blood flow through the pulmonary veins, which prevents the risk of developing pulmonary edema. Heterometric regulation of the heart can provide compensation for circulatory failure due to its defects.
The term “homeometric regulation” refers to myogenic mechanisms, for the implementation of which the degree of end-diastolic stretch of myocardial fibers does not matter. Among them, the most important is the dependence of the force of heart contraction on the pressure in the aorta (Anrep effect). This effect is that the increase in aortic pressure initially causes a decrease in systolic cardiac volume and an increase in residual end-diastolic blood volume, followed by an increase in cardiac contractile force and cardiac output stabilizes at a new level of contractile force.
Neurogenic regulation- one of the mechanisms complex system regulation of blood circulation in the human body. Neurogenic regulation is short-term and allows the body to quickly and effectively adapt to sudden changes in hemodynamics associated with changes in blood volume, cardiac output or peripheral resistance.
Humoral influences on the heart. Almost all biologically active substances contained in the blood plasma have a direct or indirect effect on the heart. These are catecholamines secreted by the adrenal medulla - adrenaline, norepinephrine and dopamine. The action of these hormones is mediated by beta-adrenergic receptors of cardiomyocytes, which determines the final result of their effects on the myocardium. It is similar to sympathetic stimulation and consists of activation of the enzyme adenylate cyclase and increased synthesis of cyclic AMP (3,5-cyclic adenosine monophosphate), followed by activation of phosphorylase and an increase in the level of energy metabolism.
The effect of other hormones on the myocardium is nonspecific. The inotropic effect of glucagon is known. Adrenal hormones (corticosteroids) and angiotensin also have a positive inotropic effect on the heart. Iodine-containing thyroid hormones increase heart rate.
The heart also shows sensitivity to the ionic composition of flowing blood. Calcium cations increase the excitability of myocardial cells.
Innervation of the heart. The heart is a richly innervated organ. A large number of receptors are located in the walls of the heart chambers and in the epicardium. Highest value Among the sensitive formations of the heart, they have two populations of mechanoreceptors, concentrated mainly in the atria and left ventricle: A-receptors respond to changes in the tension of the heart wall, and B-receptors are excited when it is passively stretched. Afferent fibers associated with these receptors are part of the vagus nerves. Free sensory nerve endings located directly under the endocardium are the terminals of afferent fibers passing through the sympathetic nerves. It is believed that these structures are involved in the development of pain syndrome with segmental irradiation, characteristic of attacks of coronary heart disease, including myocardial infarction.
Efferent innervation of the heart is carried out with the participation of both parts of the autonomic nervous system.
The bodies of sympathetic preganglionic neurons involved in the innervation of the heart are located in in gray lateral horns of the three upper thoracic segments of the spinal cord.
Derivations of the vagus nerve, passing as part of the cardiac nerves, are parasympathetic preganglionic fibers. From them, excitation is transmitted to intramural neurons and further - mainly to the elements of the conduction system.
30. Numerous experiments have shown that various products of metabolic reactions can act as irritants not only directly on cell membranes, but also on nerve endings - chemoreceptors, causing certain physiological and biochemical changes in a reflex way. In addition, physiologically active substances, carried by the bloodstream throughout the entire body, only in certain places, in the resulting organs or target cells, cause targeted specific reactions when interacting with effectors or corresponding receptor formations.
Thus, many transmitters of nervous influence - mediators, having fulfilled their main role and avoided enzymatic inactivation or reuptake by nerve endings, enter the blood, carrying out a distant (non-mediator) effect. Penetrating through histohematic barriers, they enter organs and tissues and regulate their vitality. The state of the nervous system itself depends not only on information from the environment and internal environment, but also on the blood supply and on various ingredients of the internal environment.
In this case, there is a close relationship and interdependence of nervous and humoral processes. Thus, the neurosecretory cells of the hypothalamic nuclei are the site of transformation of nervous stimuli into humoral ones, and humoral ones into nervous ones. In addition to various mediators, numerous peptides and other active compounds are synthesized in the brain, which take part in the regulation of the activity of the brain and spinal cord, and when entering the blood, the entire body. Thus, and the brain can also be called an endocrine gland.
Physiological activity liquid media org-ma is largely determined by the ratio of electrolytes and microelements, the state of synthesizing and degrading enzyme systems, the presence of activators and inhibitors, the formation and disintegration of complex protein-polysaccharide complexes, the binding and release of substrates of unbound forms, etc.
An important role in the neurohumoral regulation of hormones is played by hormones, as well as a variety of specific and nonspecific products of interstitial metabolism, united under common name metabolites. These include tissue hormones, hypothalamic neurohormones, prostaglandins, and broad-spectrum oligopeptides.
Increasing importance in the integration of neurons in the centers, in the creation of their operational constellations, in the coordination relationships between them is attached to the direct humoral background, the microsphere in the brain, created, in particular, by the secretion of the neurons themselves. This circumstance once again demonstrates the unity of nervous and humoral mechanisms.
What are the advantages of a method of regulating functions, carried out with the predominant participation of the nervous apparatus? Unlike the humoral connection, the nervous connection, firstly, has a precise direction to a specific organ and even a group of cells and, secondly, through the nerve conductors, the connection occurs at a much higher speed, hundreds of times higher than the speed of physiological propagation active ingredients. Along with the cable control method based on the “subscriber-answer” principle, as in a telephone exchange, the central apparatus of the nervous system with predominant integrative intermediate neurons provides a probabilistic control principle, flexibly adapted to a continuously changing environment and providing deterministic executive reactions.
31. The exchange of substances and energy underlies all manifestations of life and represents a whole series of processes transformation into and energy in a living organism and the exchange of energy and energy between the organism and the environment. To maintain life in the process of exchange of substances and energy, the plastic and energy needs of the organism are provided. Plastic needs are satisfied by substances used to build biological structures, and energy needs are satisfied by converting chemical energy entering the body. nutritious ingredients into the energy of high-energy and reduced compounds. Their energy is used by the body for the synthesis of proteins, nucleic acids, lipids, as well as components cell membranes and cell organelles, to carry out cellular activities involving the use of chemical, electrical and mechanical energy. The exchange of substances and energy (metabolism) in the human body is a combination of interconnected but multidirectional processes: anabolism (assimilation) and catabolism (dissimilation). Anabolism- this is the essence of biosynthesis processes organic ingredients, cell components and other structures of organs and tissues. Catabolism- this is the process of splitting complex molecules, components of cells, organs and tissues into simple ones and to the final products of metabolism. In the vast majority of animals, body temperature changes with temperature environment. Such animals that are unable to regulate their body temperature are called poikilothermic animals. Only a tiny minority of animal species during their phylogenesis acquired the ability to actively regulate body temperature; Such animals with a relatively constant body temperature are called homeothermic. In mammals, body temperature is usually 36-37°C; in birds it rises to approximately 40°C. The influence of sharp fluctuations in environmental temperature on organisms is reduced by special adaptive complexes of traits.
There are two fundamentally different types of adaptation to temperature: passive and active. The first type is characteristic of ectothermic (poikilothermic, cold-blooded) organisms (all taxa organic world, except birds and mammals). Their activity depends on the ambient temperature: insects, lizards and many other animals become lethargic and inactive in cool weather. At the same time, many species of animals have the ability to choose a place with optimal conditions of temperature, humidity and insolation (with a lack of heat, lizards bask on sunlit slabs rocks, and when there is an excess of it, they hide under stones and bury themselves in the sand). Ectothermic organisms have special adaptations for surviving cold - the accumulation of “biological antifreeze” in cells, which prevents the freezing of water and the formation of ice crystals in cells and tissues. For example, in cold-water fish such antifreezes are glycoproteins, and in plants it is sugar. Endothermic (homeothermic, warm-blooded) organisms (birds and mammals) are provided with heat through their own heat production and are able to actively regulate heat production and consumption. At the same time, their body temperature changes slightly, its fluctuations do not exceed 2–4°C even in the most severe frosts.
The main adaptations are chemical thermoregulation due to the release of heat (for example, aspiration) and physical thermoregulation due to heat-insulating structures (fat layer, feathers, hair, etc.). Endothermic, like ectothermic animals, use cooling mechanisms of moisture evaporation from the mucous membranes of the oral cavity and upper respiratory tract to lower body temperature. Fever is a typical thermoregulatory protective-adaptive reaction of an organism to the effects of pyrogenic substances, expressed by a temporary restructuring of heat exchange to maintain a higher than normal heat content and body temperature.
It is assumed that there are three types of thermoregulatory neurons in the hypothalamus: 1) afferent neurons that receive signals from peripheral and central thermoreceptors; 2) intercalary, or interneurons; 3) efferent neurons, the axons of which control the activity of effectors of the thermoregulation system.
32. Exchange of goods between the organism and the external environment - the main and integral property of life. The data of modern biochemistry show with complete certainty that all human organs and tissues without exception (even bones and teeth) are in a state of continuous exchange of substances, constant chemical interaction with other organs and tissues, as well as with the surrounding organism. external environment. It has also been established that intensive exchange of substances occurs not only in the cytoplasm of the cell, but also in all parts of its nuclear apparatus, in particular in the chromosomes.
The basis of metabolism is the processes of catabolism and anabolism.
Catabolism– the totality of enzymatic reactions occurring in a living organism that break down complex organic substances, including food ones. In the process of catabolism, which is also called dissimilation, the energy contained in chemical bonds large organic molecules, and storing it in the form of energy-rich ATP bonds. Catabolic processes include cellular respiration, glycolysis, and fermentation. The main end products of catabolism are water, carbon dioxide, ammonia, urea, lactic acid, which are excreted from the body through the skin, lungs and kidneys.