69. The role of mediators in the mechanism of formation of epsp and tpps.

The effect of the mediator on the postsynaptic membrane is to increase the permeability to sodium. The appearance of a stream of sodium ions from the synaptic cleft leads to membrane depolarization and causes the generation of an exciting postsynaptic potential (acetylcholine, norepinephrine, serotonin , dopamine, glutamate ).

For chem. synapses are characterized by a synoptic delay in the excitation (0.5 ms) and the development of postsynaptic potential in response to a presynaptic impulse. When excited, it manifests itself in depolarization of the membrane, and during inhibition, in hyperpolarization , as a result, inhibitory postsynaptic potential (glycine, GABA) develops.

 

 

70. Characterization of epsp and tpsp in duration and amplitude.

The development of EPSP is characterized by the fact that they arise after the time after the arrival of PD in the presynaptic ending (delay). After this, the amplitude increases 1–1.5 ms (rise time), and then its decrease is observed, which lasts 4–6 ms (fall time). Amplitude from 0.12 - 5.0 mV, time 5-10 ms.

TPPS is similar to EPSP, but it has a longer latent period and shorter decay time (3 ms). Amplitude - 1.37-3.44 mV, time - 5-12 ms.

 

71. The number of synapses on spinal cord motor neurons .

The more synapses on the surface of a nerve cell, the more irritations are perceived and the wider the scope of activity. On the bodies of large motor neurons, there are 15-20 thousand synapses. The largest amount - 50% is located on dendrites. Many of them are located on the spine-shaped outgrowths, which increase the perceptual surface of the neuron.

 

72. The mechanism of integration of epsp and tpps neuron.

The resting potential of the membrane may decrease — depolarization (upon excitation) and increase — hyperpolarization (upon inhibition).

Under the influence of EPSP, membrane portions adjacent to the synapse are depolarized, then depolarization reaches the axon knoll, where excitation occurs, propagating to the axon.

In TPPS ax . the end of the synapse is depolarized, which leads to the appearance of weak currents, causes the mobilization and release of special inhibitory mediators into the synaptic cleft. They change the ionic potential of the membrane in such a way that pores with a diameter of 0.5 ni open in it. They do not allow sodium to pass through, but release potassium from the cell to the outside. Hyperpolarization occurs .

 

 

73. Ultrastructure of the neuromuscular synapse . Neuromuscular synapses of skeletal muscles have a number of characteristic features. The presynaptic nerve ending that innervates the skeletal muscles forms a kind of thickening covered with a presynaptic membrane. There is a space between the nerve ending and the effector cell, the so-called synaptic cleft. It separates the nerve ending from the membrane of the effector cell, called the postsynaptic membrane. The postsynaptic membrane, unlike the presynaptic, has protein chemoreceptors for biologically active (mediators, hormones), drugs and toxic substances. An important feature of the postsynaptic membrane receptors is their chemical specificity, i.e., the ability to enter into biochemical interaction only with a certain type of mediator. The structural features of the neuromuscular synapse determine its physiological properties.

    Synapse properties. 1. Unilateral conduction due to the presence of receptors sensitive to the mediator only in the postsynaptic membrane. 2. The synaptic delay of the excitation, associated with the low diffusion rate of the mediator into the synaptic cleft compared to the speed of the pulse through the nerve fiber. 3. Low lability and high fatigue of the synapse, due to the propagation time of the previous pulse and the presence of a period of absolute refractoriness. 4. High selective sensitivity of the synapse to chemicals, due to the specificity of the chemoreceptors of the postsynaptic membrane.

 

74. There are two types of cholinergic receptors - nicotinic and muscarinic . On the postsynaptic membrane of skeletal muscles are cholinergic receptors of the nicotine type. When 2 AX molecules bind to special sites on the nicotinic type cholinergic receptor , an ion channel opens for Na + ions . Na + ions enter the cell according to the concentration gradient, forming an incoming sodium current. This leads to a slight depolarization of the postsynaptic membrane and the emergence of a local response - the potential of the end plate (PCP) . Such a small depolarization is due to the fact that ion channels in the postsynaptic membrane of the skeletal muscle (or end plate) have selectivity. When the amplitude of the local response reaches a threshold level, fast selective sodium channels open in the peri-synaptic region, as a result of which PD is generated. After activation of the cholinergic receptor , ACh is cleaved by the enzyme acetylcholinesterase (AChE) into choline and acetic acid. Choline enters the presynaptic terminal via a reuptake system . Residues of acetic acid slowly diffuse into the peri - synaptic space and acidify it.

 

75. QUANTUM mediator - an indivisible portion of chemically active in the islands .

Quantum release of a neurotransmitter is the isolation of a multimolecular portion (quanta) of a neurotransmitter from presynaptic nerve terminals .

If the body wasted a certain number of neurotransmitters in the process of life, then neural cells then form ordinary material, begin to form new material for future work. If the expected work did not arise, the material accumulates in excess, being in secretory containers - vesicles. And then spontaneous exocytosis of mediators begins .

The miniature potential of the end plate is the potential of the end plate arising from the spontaneous release of acetylcholine contained in one presynaptic vesicle.

 

76. Inactivation is the process of removing a mediator from a receptor to prevent too long (strong) signal transmission.

In each particular synapse, one of three ways of inactivation is used :

1) the destruction of the mediator using an enzyme;

2) transfer of the mediator to the presynaptic ending;

3) mediator transfer to glial cells.

Way 1. The enzyme is usually located on the postsynaptic membrane, but can be located in the synaptic cleft; this method is the fastest, although not economical (loss of a valuable substance - a mediator)

Dopamine inactivation : reuptake and subsequent reuse or destruction using MA O ( enzyme monoamine oxidase; breaks down a variety of monoamines, including mediators and hormones.)

Way 2. "Re-capture" of the mediator with a special protein pump (located on the presynaptic membrane).

Very economical, since then the neurotransmitter can be loaded into the vesicle and reused . ( Glutamic acid, GABA ...)

Way 3. Capture of a mediator by a protein pump located on the membrane of a glial cell ( oligodendrocyte ).

In this case, the mediator is destroyed inside the glial cell (mediators, the synthesis of which is not difficult for the neuron, are inactivated).

From the synaptic cleft, Glu is transferred to glial cells, where it is converted to glutamine ( Gln ) (using the enzyme  glutamine synthetase ).

 

77. Muscle relaxants - drugs that reduce the tone of skeletal muscle with a decrease in motor activity up to complete immobilization.

The mechanism of action is the blockade of H-cholinergic receptors in synapses stops the supply of a nerve impulse to the skeletal muscles, and the muscles stop contracting. Relaxation goes from top to bottom, from the facial muscles to the tips of the toes. The last diaphragm relaxes. Conductivity recovery is in the reverse order. The first subjective sign of the end of muscle relaxation is the patient's attempt to breathe independently. Signs of complete decure : the patient can raise and hold his head for 5 seconds, tightly squeeze his hand and breathe independently for 10-15 minutes without signs of hypoxia.

The effect on the M-cholinergic receptors of the heart, smooth muscles and vagus nerve depends on the drug and dose. Some muscle relaxants can trigger histamine release.

Do not pass through the BBB. Passing through PB depends on the drug and dose. Not soluble in fats. Binding to blood proteins depends on the drug.

Application:

1. Providing conditions for tracheal intubation.

2. Ensuring muscle relaxation during surgical interventions to create optimal working conditions, as well as the need for muscle relaxation during certain diagnostic procedures (for example, bronchoscopy).

4. The elimination of convulsive syndrome with the ineffectiveness of anticonvulsants.

5. Blockade of protective reactions to cold in the form of muscle tremors and muscle hypertonicity with artificial hypothermia.

6. Muscle relaxation during reposition of bone fragments and reposition of dislocations in joints where there are powerful muscle masses.

 

 

78.

 

79.

The main mediator of the sympathetic nervous system is norepinephrine, parasympathetic acetylcholine . The sympathetic nervous system mediates an organism response such as "fight or flight." The expansion of the bronchi and the increase in pulmonary ventilation, the increase in the frequency and strength of heart contractions, the narrowing of the arteries of the skin, the gastrointestinal tract, the kidneys and the expansion of the arteries of the muscles, myocardium, lead to an increase in the delivery of oxygen to the muscles and heart, due to which they increase contractions. This is facilitated by increased decomposition of glycogen in the liver and fat in adipose tissue, which improves the supply of muscle, heart and brain with glucose and fatty acids. The predominance of the activity of the parasympathetic system provides reactions such as "rest and recovery", which leads to the restoration of the body's forces. At the same time, strength, heart rate and airway clearance decrease, skeletal muscle arteries narrow, and the gastrointestinal tract expand. This leads to a decrease in blood flow in the muscles, myocardium and an increase in the digestive tract, which enhances digestion.

The mediator in the peripheral synapses of the parasympathetic nervous system is acetylcholine, to which there are two types of receptors: M- and H-cholinergic receptors . This division is based on the fact that M-cholinergic receptors lose sensitivity to acetylcholine under the influence of atropine (isolated from a mushroom of the genus Muscaris ), and N-cholinergic receptors - under the influence of nicotine.

α1 and β1 receptors are localized mainly on postsynaptic membranes and react to the action of norepinephrine released from the nerve endings of postganglionic neurons of the sympathetic division.

α2 and β2 receptors are extrasynaptic and are also present on the presynaptic membrane of the same neurons. Both adrenaline and norepinephrine act on α2 receptors. β2 receptors are mainly sensitive to adrenaline. On the α2 receptors of the presynaptic membrane, norepinephrine acts on the principle of negative feedback - it inhibits its own secretion. Under the action of adrenaline on the β2-adrenoreceptors of the presynaptic membrane, the release of norepinephrine increases.

Briefly describe the importance of receptors as follows:

α1 - are localized in arterioles , stimulation leads to spasm of arterioles , increased pressure, decreased vascular permeability and decreased exudative inflammation.

α2 - mainly presynaptic receptors, are a “negative feedback loop” for the adrenergic system, their stimulation leads to a decrease in blood pressure.

β1 - are localized in the heart, stimulation leads to an increase in the frequency and strength of heart contractions, in addition, leads to an increase in myocardial oxygen demand and an increase in blood pressure. They are also localized in the kidneys, being receptors of the juxtaglomerular apparatus.

β2 - localized in the bronchioles, stimulation causes the expansion of bronchioles and the removal of bronchospasm . The same receptors are located on the liver cells, the action of the hormone on them causes glycogenolysis and the release of glucose into the blood.

β3 - are in adipose tissue. Stimulation of these receptors enhances lipolysis and leads to the release of energy, as well as to increase heat production.

 

 

Number 80

. Acetylcholinesterase plays a key role in the processes of neurohumoral and synaptic transmission: in cholinergic synapses it catalyzes the hydrolysis of acetylcholine, and, as a result, stops the effect of this mediator on the cholinergic receptor , which is responsible for the excitation of nerve fiber. When AChE is inhibited, the release of receptors from acetylcholine occurs very slowly (only through diffusion), and the transmission of nerve impulses is blocked at the level ( neurotransmitter <-> postsynaptic membrane). This causes a disorganization of the body's processes, and in severe poisoning it can be fatal.

Monoamine oxidase (MAO) is an enzyme that catabolizes monoamines through their oxidative deamination . MAO destroys both endogenous monoamines - neurotransmitters and hormones, and exogenous ones - which enter the body with food or in drugs and psychoactive substances (surfactants). Thus, this enzyme plays an important role in maintaining constant concentrations of endogenous monoamines in tissues, which is especially important for nervous tissue, and also restricts their ingestion into the body through food and is involved in the metabolism of hazardous biologically active substances structurally similar to endogenous monoamines.

 

. No. 81 Electric synapses. Morphologically represent the merger, or rapprochement, of the membrane sections. In the latter case, the synaptic cleft is not continuous, but is interrupted by bridges of full contact. These bridges form a repeating cellular structure of the synapse, moreover, the cells are limited by areas of adjacent membranes, the distance between which in the synapses of mammals is 0.15-0.20 nm. In the areas of membrane fusion, there are channels through which cells can exchange certain products. In addition to the described cellular synapses, other electrical synapses are distinguished - in the form of a continuous gap; the area of ​​each of them reaches 1000 μm, as, for example, between the neurons of the ciliary ganglion.

Electrical synapses have one-way excitation. This can be easily proved by recording the electric potential at the synapse: when the afferent pathways are irritated, the synapse membrane is depolarized, and when the efferent fibers are irritated, it becomes hyperpolarized . It was found that neuronal synapses with the same function have bilateral holding excitation (e.g. synapses between two sensitive cells) and synapses between raznofunktsionalnymi neurons ( sensory and motor) have a one-way conducting. The functions of electrical synapses are primarily to ensure urgent reactions of the body. This, apparently, explains their location in animals in structures that provide a flight response, escape from danger, etc.

The electrical synapse is relatively fatigued, resistant to changes in the external and internal environment. Apparently, these qualities along with speed provide high reliability of its work.