Excitable tissue – 03
Excitable tissue – 03
01. Physiological (functional) lability of the tissue. Methods for its determination. Characteristics of excitability and lability of nervous and muscular tissues. Rhythm repetition (A. A. Ukhtomski).
Lability (functional mobility) is the ability of the excitable tissue to generate a certain number of impulses (rate) of excitation per unit of time (Vvedensky N. E.).
Its value is 500-1000 imp/sec for the nervous tissue, 200-250 imp/sec for the muscular tissue, 100-125 imp/sec for the chemical synapse.
Nervous tissue has greater lability than muscle tissue. Its value depends on the functional state of the tissue.
It can change in the course of a prolonged action of the stimulus, that is, the tissue can increase its lability in the process of vital activity.
Rhythm assimilation is the ability of excitable tissue to change the generated number of impulses of excitations during prolonged stimulation (A. A. Ukhtomsky).
02. Parabiosis (N. E. Vvedenskiy). Transient phases from excitation to inhibition. Parabiosis and inhibition.
Parabiosis is a phenomenon of stable excitation in partially damage tissue.
When the tissue is partially damaged, then phases of parabiosis develop:
1. equality phase: tissue response in the same attenuated manner to low and high intensive stimuli;
2. paradoxical phase: tissue reacts to less intensive stimuli more actively than to high intensive stimuli;
3. inhibitory phase: tissue does not react to any stimuli.
3. Characteristics of the structural and functional organization of the synapse. Classification of synapses.
- Nervous tissue Nervous tissue as an excitable tissue has a strong ability to provide transmission of information at a distance (conductivity).
- This is realized along the nerve fibers or through the interaction of two cells.
- In 1890s the main postulates of the neural theory were formulated (Santiago Ramóny Cajal – a Spanish scientist, according to his opinion the connection between neurons is carried out by means of contacts of the cell membranes, and not by cytoplasmic continuity (the nerve tissue is not syncytium).
Ø Synapse
Synapse (from Greek syn – “together” and haptein – “to clasp”)is a highly specialized structure that provides a signal transmission from one cell to another.
This term was introduced by an English physiologist C. S. Sherrington in 1897.
Synapse provides the processes of inter-neural communication, integrating the activity of the central nervous system.
In the structure of a synapse, presynaptic and postsynaptic terminals are distinguished, as well as the synaptic cleft located between them. There are several synapse types.
Synapse classification:
·
According to the position in the body:
- central (in the CNS);
- peripheral (in nerves, muscles, organs).
· According to the contacting cells:
- interneuronal;
- neuroeffector (neuromuscular, neurosecretory);
- neuro-receptor.
· According to the mechanism of signal transmission:
- chemical;
- electrical;
- mixed.
· According to the effect:
- excitatory synapses;
- inhibitory synapses.
04. General characteristics of electrical synapses. The role of connexons. The conceptual idea of ephapse.
An electrical synapse is an intercellular formation that provides the transmission of the electrical impulse by creating an electrical current between the presynaptic and postsynaptic terminals.
In this synapse, the cell membranes contact closely each other, forming a narrow cleft 2 nm wide (synaptic cleft).
On these membranes there are specific protein complexes consisting of six subunits and arranged in such a manner that a pore filled with water that passes through the bilayer of the cell membrane – connexons – is formed at their center.
Most electrical synapses are excitatory. This type of synapse is not widely represented in mammals.
In the adult body, electrical synapses are found in the retina of the eye, in the brainstem, in vestibular roots and lower olive.
Electrical synapse properties:
- fast conductance (transmission rate is significantly higher than in chemical synapses);
- weakness of trace effects (there is practically no summation of serial signals);
- high reliability of excitation transmission;
- plasticity;
- double-way condactance (as compared to chemical synapse).
05. Features of excitation transmission in chemical synapses. Ionotropic and metabotropic receptors. Mediators, their classification and role.
Ø Chemical synapse
A chemical synapse is an intercellular formation that provides signal transmission with the help of a chemical transmitter (mediator), which serves as a signal molecule, ensuring the specificity of the functioning of a cell.
The mediator is able to interact with the receptor. As a rule, it is a protein molecule that has a certain structural and functional organization.
The release of the mediator from the vesicles is accomplished by exocytosis.
In this process, an important role is assigned to special synapsin proteins, which are phosphoproteins associated with the membrane of synaptic vesicles.
To activate it, Ca2+ ions are needed.
Vesicular proteins involved in exocytosis are:
- synaptobrevin – 18,000 Da – involved in the formation of complexes between vesicle membrane and presynaptic membrane,
- synaptotagmin – 65,000 Da, Ca-binding protein, causes the Ca-dependent process of fusion of vesicle membrane and presynaptic membrane,
- synaptophysin – forms the pore of vesicle fusion with presynaptic membrane.
The resulting mediator-receptor complex causes a change in the conformation of a certain region of the biomembrane and the subsequent definite cellular response.
Chemical synapse properties:
- "physiological valve" principle;
- participation of chemical mediator;
- synaptic delay;
- Dale's principle;
- transformation of excitation rhythm;
- synaptic plasticity: synaptic depression (weakening) and facilitation (strengthening, potentiation or augmentation);
- fatigability;
- summation phenomenon, obedience to the law of force;
- low lability;
- high sensitivity to chemical factors.
Ø Mediators are chemical substances involved in the transmission of excitation or inhibition from one excitable cell to another.
Dale's principle (or Dale's law) is a rule that only one mediator is released by one neuron at all of its synaptic connections to other cells.
Synaptic delay is the time necessary to conduct the electrical impulse in the synapse (0.2-0.5 msec).
A complex reflex arc contains a large number of synapses, which increases the response time of the reflex.
Various approaches to the classification of chemical synapses are known. According to the mediator name (for chemical synapses):
- cholinergic;
- adrenalinergic;
- dopaminergic;
- GABAergic;
- glutamatergic;
- aspartatergic;
- peptidergic;
- purinergic, etc.
Ø Membrane receptors are protein molecules that are complementary to the corresponding chemical mediators and are able to monitor the functional state of the membrane structural elements (opening channels, changing the conformation of molecules, etc.).
By the receptor organization, ionotropic and metabotropic synapses are distinguished.
Ionotropic receptors consist of several subunits, which form an ion channel in the cell membrane. Binding of the mediator to this receptor leads to the opening of the channel due to the allosteric effect.
Metabotropic receptors are structures associated with intracellular intermediary systems, changes in their conformation when bound to a ligand lead to a cascade of reactions, and, ultimately, to a change in the functional state of the cell.
As a rule, chemical synapses provide the transmission of the excitation process, but can also initiate the inhibition processes.
In exciting synapses due to the formation of the mediator-receptor complex, the permeability of postsynaptic membrane for Na+ ions increases, which leads to the depolarization of the membrane and the onset of an excitatory postsynaptic potential (EPSP).
In inhibitory synapses, the permeability of postsynaptic membrane for ions, primarily K+ and Cl-, increases, which causes hyperpolarization of the membrane and, accordingly, an inhibitory postsynaptic potential (IPSP) occurs.
06. The mechanism of excitation transmission in the neuromuscular synapses.
Neuromuscular synapse (junction) One of the most widespread chemical synapses in the body is neuromuscular junction.
In this structural formation, the main mediator is acetylcholine.
In the presynaptic terminal there are vesicles with a mediator. They can contain up to 6-8 thousand molecules of this mediator.
The formation of acetylcholine occurs with the participation of the enzyme acetylcholine transferase. Under the action of the nerve impulse, membrane depolarization arises, the opening of special potential dependent or voltage-dependent Ca2+ channels and influx of Ca2+ inside the motor nerve endings occurs.
The increase in Ca2+ concentration activates Ca2+-culmodulin dependent protein kinase II, which phosphorylates synapsin, synaptotagmine, synaptobrevin and other SNARE (an acronym derived from SNAP – “Soluble N-ethylmaleimide-sensitive factor Attachment Protein” and RE – receptor) proteins, which causes the release of the mediator into the synaptic cleft via exocytosis.
Acetylcholine is secreted discretely (4*104), as if in portions. One nerve impulse initiates a synchronous release of 100-200 portions of the mediator within 1 msec.
The reserves of acetylcholine in the nerve ending are sufficient to generate 2,500-5,000 impulses.
Mediators, diffusing to the postsynaptic membrane receptors, form the corresponding complexes with it.
Acetylcholine receptors are lipoproteins (location density on postsynaptic membrane is about 13.000/m2).
There are receptors sensitive to nicotine and muscarin, respectively, N- and M-cholinergic receptors, each of which consists 64of 5 protein subunits forming an ion channel in the postsynaptic membrane.
N-cholinergic receptors are blocked by a special substance – curare – and belong to ionotropic receptors (ligand gated ion channels). Its activation leads to a change in the ion permeability of the postsynaptic membrane and its depolarization.
The interaction of acetylcholine with a receptor that represents an ion channel leads to the appearance of the potential of an end plate, which initiates the formation of an action potential that propagates through the muscle fiber and causes a muscle contraction.
Realization of the synaptic process provides the transfer of regulatory sygnal.
Under the influence of the acetylcholinesterase enzyme, acetylcholine is cleaved to choline and acetic acid, as a result of which synaptic transmission ceases.
7. Functions and physiological properties of the nerve fibers. The laws of the excitation conduction in the peripheral nerves.
8. Mechanisms of excitation conduction along unmyelinated and myelinated nerve fibers. Functional characteristics of the nerve fibers, their classification.
Nerve fibers, being the neurons processes, transmit information along the neuron and from it to other neurons or to receptor or to effector cell.
Nerve fibers are divided into medullated fibers (myelinated) and nonmedullated (unmyelinated) fibers.
In the ANS, unmyelinated fibers predominate, and in the efferent nerves of skeletal muscles – myelinated fibers.
The myelin sheath of the myelinated fibers covers them from all sides, interrupting at regular intervals, forming nodes of Ranvier.
Myelin sheath performs an isolating and trophic function in the myelinated nerve fibers. Properties of excitation conduction along nerve fibers:
- morphological and physiological integrity;
- double-way conductance;
- nerve impulse spread along nerve fiber in both directions with the same speed;
- double-way excitation coductance occurs without decrement;
- in different fibers, excitation is transmitted at different rates;
- higher speed of excitation conductance as compared to transmission through axoplasm or with blood flow;
- nerve impulse spread separately from each other along isolated nerve fibers;
- low fatigability.
The excitation conductance along nerve fibers is based on ionic mechanisms for generating action potentials.
The action of the stimulus in unmyelinated fibers leads to the depolarization of the membrane.
Between the excited and unexcited areas of the nerve fiber, local currents arise, leading to the occurrence of action potentials in unexcited areas.
Thus in unmyelynated fibers action potential spreads along nerve membrane in wave-like (or cable-like) manner.
Myelin sheath serves as a dielectric. Node of Ranvier has a length of about 1 mkm, and the distance between them is about 2000 mkm.
Conductance of excitation along myelinated nerve fibers is carried out by saltatory mechanism (saltario = leap).
Local currents occur in one node of Ranvier and spread to neighboring ones, causing depolarization and generation of the action potential.
The action potential "leaps" from one node to another.
In the nodes of Ranvier there is a higher density of sodium channels, 200 times greater than in the membrane of the giant squid axon.
In myelinated fibers, excitation propagates (as compared to unmyelinated fibers of equal thickness) much more quickly and at lower energy expenditure (the rate of attenuation of local currents is less pronounced).
As a rule, the speed of electrical impulse conductance along the nerve fiber increases with increasing diameter. According to their functional characteristics, nerve fibers are divided into 3 main groups.
