Hyperpolarizing inhibition

What is inhibition in physiology?

Inhibition is an active biological process that prevents the development of excitation or terminates an already initiated process. It is a temporary phenomenon that regulates the level of excitation. In the central nervous system (CNS) and internal organs, processes of excitation and inhibition constantly alternate with each other. Inhibition can occur either as an independent functional process or as a result of the interaction of two excitations.

Historically, two types of inhibition are distinguished:

• Peripheral inhibition — discovered by the Weber brothers (A. and E. Weber) in 1847 using the effect of the vagus nerves (n. vagus) on cardiac activity as an example.
• Central inhibition — occurs directly within the CNS. This process was first investigated and described by I.M. Sechenov in 1862.

How does the mechanism of hyperpolarizing inhibition work?

This type of inhibition is implemented at postsynaptic membranes. Its occurrence strictly requires the participation of an inhibitory interneuron.

The process includes the following stages:

1. Excitation arrives via the first axon and activates the inhibitory neuron.
2. The inhibitory neuron directly acts on the postsynaptic membrane of the target neuron. This typically occurs at an axo-somatic synapse, where the cell body (soma) of a cell, such as a pyramidal neuron, is affected.
3. The released inhibitory neurotransmitter acts on the postsynaptic membrane.
4. An increase in the magnitude of the membrane charge occurs — hyperpolarization.
5. As a result, the excitation threshold of the main neuron increases, and an inhibitory postsynaptic potential (IPSP) develops.

The end result of this process is a decrease in tissue excitability and the inability to generate an action potential.

Which neurotransmitters mediate the process?

Depending on the released neurotransmitter, inhibitory neurons providing hyperpolarization are divided into several types:

• Glycinergic neurons — release the neurotransmitter glycine, providing postsynaptic inhibition.
• GABAergic neurons — release gamma-aminobutyric acid (GABA). They are capable of providing both postsynaptic and presynaptic inhibition.
• Mixed-type neurons — simultaneously release both glycine and GABA (co-release of neurotransmitters occurs from a single axon). Such neurons are found predominantly in the brainstem.

What is its clinical significance (using pain suppression as an example)?

Synaptic mechanisms of pain suppression are implemented at the spinal level — in the dorsal horns of the spinal cord, where the terminals of primary afferents and interneurons are located.

At the postsynaptic level, hyperpolarization of interneuron membranes occurs, which suppresses their activity. Combined with presynaptic inhibition, which reduces the release of "nociceptive" pain neurotransmitters — glutamate, neurokinins, and substance P — this leads to the blockade of pain impulse transmission to higher CNS centers.

What is its place in the electrophysiological classification?

In addition to hyperpolarizing inhibition, which reduces excitability through the action of inhibitory neurotransmitters, two other membrane mechanisms of inhibition are distinguished:

• Persistent depolarizing inhibition — occurs at a high frequency of excitation. Due to an excess of excitatory neurotransmitter (referred to as the phenomenon of pessimal inhibition) or the absence of an inhibitory enzyme, sustained activation of sodium and potassium channels occurs. The membrane cannot return to the resting state, the absolute refractory period is prolonged, and the difference between the current membrane charge and the critical level of depolarization (CLD) increases. The process is analogous to the phenomena of parabiosis or accommodation. It can also occur under the action of inhibitory neurotransmitters due to specific membrane properties.
• Stabilization inhibition — occurs under the action of a number of biologically active substances. A blockade of sodium permeability of cell membranes occurs without altering the resting potential, making the generation of excitation impossible.

Class and exam questions

What else to study on this topic

• Presynaptic inhibition
• Persistent depolarizing inhibition
• Stabilization inhibition
• Inhibitory postsynaptic potentials (IPSPs)

Other topics in "Physiology concepts"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.