The inhibitory postsynaptic potential is a type of postsynaptic potential , which leads to the fact that the activity of the postsynaptic neuron decreases, and the occurrence of an action potential becomes less likely . [one]
The opposite of inhibitory postsynaptic potential is the exciting postsynaptic potential , which leads to the fact that the activity of the postsynaptic neuron increases, and the appearance of the action potential becomes more likely .
The emergence of various types of postsynaptic potentials is possible in various types of chemical synapses that use the secretion of certain neurotransmitters to ensure neurotransmission (intercellular signal transmission).
Braking (inhibitory) presynaptic neurons secrete inhibitory neurotransmitters into the synapse (for example, such as GABA , glycine , serotonin , depending on the type of neuron). These inhibitory neurotransmitters then bind to the corresponding specific inhibitory postsynaptic receptors. As a result of activation of these inhibitory receptors, changes in the activity of the postsynaptic neuron occur, in particular, ion channels open or close (for example, the channels of chlorine ions in the case of the GABA-A receptor or the channels of potassium ions in the case of the 5-HT 1A receptor ). This leads to a change in the electrical conductivity of the membrane of the postsynaptic neuron. An electric current is generated that changes the postsynaptic potential - the postsynaptic membrane becomes more electronegative (more negatively charged). If the initial membrane potential is between the resting threshold and the threshold of occurrence of the action potential, then depolarization of the cell may occur as a result of the action of this inhibitory potential. The inhibitory postsynaptic potentials also lead to a change in the membrane permeability for chlorine ions, since as a result of a change in the membrane potential, the electrostatic force acting on the chlorine channels changes. [2] Microelectrodes can be used to measure post-synaptic potentials in excitatory and inhibitory synapses.
In general, the resulting postsynaptic potential of the cell depends on a combination of factors: types and combinations of receptors and ion channels of the cell that are simultaneously exposed, the nature of the effects ( agonistic or antagonistic ), the initial postsynaptic potential of the cell, the reverse potential, the threshold for the appearance of the action potential, the permeability of the ion channels of the cell for certain ions, as well as the gradient of the concentration of ions inside and outside the cell. All this combination of factors ultimately determines whether the cell will be in a state of excitement or in a state of rest or even oppression. The inhibitory postsynaptic potentials are always aimed at decreasing (making electronegative) the membrane potential of the cell and keeping it below the threshold of occurrence of the action potential. Thus, inhibitory postsynaptic potential can be considered as a kind of “temporary hyperpolarization” of the cell. [3] The inhibitory and excitatory postsynaptic potentials compete with each other at the set of synaptic terminals of the neuron. Their summation determines whether or not the action potential generated by the presynaptic cell at a particular synapse will be repeated (regenerated) by the same action potential on the postsynaptic membrane. The same summation of all available potentials also determines what the reaction of the postsynaptic cell to the next, “one more”, inhibitory or exciting signal will not reach the value of the action potential. Some typical neurotransmitters involved in the generation of inhibitory postsynaptic potentials are GABA and glycine, and in many, but not all, cases (depending on the type of receptor), serotonin.
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This system works in such a way that [1] inhibitory postsynaptic potentials are summed over time with subthreshold or suprathreshold exciting potentials, as a result of which the resulting postsynaptic potential decreases. The modulo-equivalent excitatory (positive) and inhibitory (negative) postsynaptic potentials add up to a neutral state, mutually canceling each other's effect on the cell. The balance between excitatory and inhibitory postsynaptic potentials is very important for integration by the cell of all electrical and chemical information coming from various excitatory and inhibitory synapses.
Additional factors
The size of the neuron can also affect the effect that the inhibitory postsynaptic potential has on the cell. Simple and instantaneous temporary summation of postsynaptic potentials takes place in neurons of a relatively small size, while in large neurons, a greater number of synapses, metabotropic and ionotropic receptors, as well as the presence of long axons and a greater distance from the synapses to the neuron’s body, allow neurons to continue electric and chemical communication with other neurons (that is, remain in a state of excitement), despite the presence of inhibitory potentials at synapses remote from the body, The inhibitory signal “travels” to the cell body.
Inhibitor molecules
GABA is a very common inhibitory neurotransmitter (a neurotransmitter whose effect leads to the generation of inhibitory postsynaptic potential) in the nervous system and retina of mammals. [1] [4] GABA receptors are pentamers, most often consisting of three different subunits (α, β, γ), although there are several other subunits (δ, ε, θ, π, ρ) and possible configurations of the GABA receptor . Open channels are selectively permeable to chlorine or potassium ions (depending on the type of receptor) and allow these ions to pass through the membrane. If the electrochemical potential of the ion current arising in this case is more negative than the threshold for the action potential, then the change in the electric charge (potential) of the membrane and its conductivity resulting as a result of this ion current (which itself is a consequence of the activation of the GABA receptor) leads to the resultant the postsynaptic potential becomes lower (more electronegative) than the threshold for the appearance of the action potential, and this reduces the likelihood of the postsynaptic neuron to generate potential l steps. Glycine molecules and receptors act in much the same way in the nervous system and in the retina.
Inhibitory receptors
There are two types of inhibitory receptors:
Ionotropic receptors
Ionotropic receptors (also known as ligand-opening ion channels) play an important role in the rapid generation of inhibitory postsynaptic potentials. [1] The neurotransmitter binds to a specific receptor domain — the so-called ligand-binding site or domain of the receptor located on the outer side of the cell’s surface membrane (facing the synaptic cleft). This leads to a change in the spatial configuration of the receptor and to the opening of the ion channel in it, which is formed inside the endo-membrane (passing through the membrane) domain of the receptor. As a result, there is a fast incoming or outgoing ion current - inside or outside the cell. Ionotropic receptors are capable of producing very rapid changes in postsynaptic potential - within milliseconds after the potential is generated by a presynaptic cell. Ion channels can affect the amplitude and temporal characteristics of the action potential of the cell as a whole. Ionotropic GABA receptors conjugated to chlorine ion channels are the target of many drugs, in particular barbiturates, benzodiazepines, GABA analogues and agonists, GABA antagonists such as picrotoxin. Alcohol also modulates ionotropic GABA receptors.
Metabotropic receptors
Metabotropic receptors, most of which belong to the family of G-protein-coupled receptors, do not contain ion channels built into their structure. Instead, they contain an extracellular ligand-binding domain and an intracellular binding domain with a primary effector protein, which is most often a G-protein . [1] The binding of an agonist to a metabotropic receptor leads to a change in receptor configuration in which the primary effector protein is activated. For example, in the case of a G-protein, activation of a receptor associated with it leads to the dissociation of the β- and γ-subunits of the G-protein in the form of a βγ-dimer and to their activation of a number of “additional” intracellular signaling pathways (in particular, en: GIRK ), while the activated α-subunit of the G-protein changes the activity of the classical adenylate cyclase pathway (increases in the case of stimulating G s protein and inhibits in the case of inhibitory G i ). This, in turn, leads to a change in the intracellular concentration of the secondary mediator - cyclic AMP - increase, in the case of an increase in adenylate cyclase activity, or decrease, in the case of a decrease. A change in the concentration of cyclic AMP affects the activity of cAMP-dependent protein kinase A , a secondary effector. An increase or decrease in the activity of protein kinase A triggers a downward effector cascade up to N-order effectors. In particular, ion channels open or close.
Inhibiting metabotropic receptors are always associated with an inhibitory subtype of G-protein, that is, with G i . Thus, they inhibit the activity of adenylate cyclase and reduce the concentration of cyclic AMP, thereby effectively inhibiting the activity of protein kinase A. In addition, they activate the incoming flow of potassium ions through GIRK , activated by the βγ-dimer of the G-protein, and inhibit the activity of calcium channels, which causes hyperpolarization cells. In this way, the metabotropic GABA receptors (heterodimers of the R1 and R2 subunits) are arranged. The 5-HT1A receptor is similarly arranged.
Metabotropic inhibitory receptors generate slow inhibitory postsynaptic potentials (lasting from milliseconds to minutes). They can be activated simultaneously with ionotropic (with some types of ionotropic receptors they can form a “receptor doublet” - a heterodimer) in the same synapse, which allows the same synapse to generate both fast and slow inhibitory potentials.
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See also
- Exciting postsynaptic potential
- GABA
- Glycine
- Postsynaptic potential
Notes
- ↑ 1 2 3 4 5 Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008.
- ↑ Thompson SM, Gahwiler BH. ACTIVITY-DEPENDENT DISINHIBITION .1. REPETITIVE STIMULATION REDUCES IPSP DRIVING FORCE AND CONDUCTANCE IN THE HIPPOCAMPUS INVITRO. (English) // Journal of Neurophysiology : journal. - 1989. - Vol. 61 . - P. 501-511 .
- ↑ Levy et al. Principles of Physiology. 4th ed. (PA): Elsevier; 2005.
- ↑ Chavas J., Marty A. Coexistence of excitatory and inhibitory GABA synapses in the cerebellar interneuron network. (English) // Journal of Neuroscience : journal. - 2003. - Vol. 23 . - P. 2019-2031 .