What Is Inhibition in Physiology?
Inhibition is an active biological process that prevents the development of excitation or arrests an ongoing excitatory process. It is a transient phenomenon that regulates the level of neuronal activity. In the central nervous system (CNS) and internal organs, processes of excitation and inhibition continuously alternate. Inhibition can arise as an independent functional process or as a result of the interaction between two excitatory inputs.
Historically, two types of inhibition are distinguished:
- Peripheral inhibition — discovered by the Weber brothers (A. and E. Weber) in 1847 while studying vagal (n. vagus) influence on cardiac activity.
- Central inhibition — occurs directly within the CNS. This process was first investigated and described by I.M. Sechenov in 1862.
What Is the Mechanism of Hyperpolarization Inhibition?
This type of inhibition is realized at postsynaptic membranes. Its occurrence strictly requires the participation of an inhibitory interneuron.
The process involves the following steps:
- An excitatory impulse arrives via the primary axon and activates an inhibitory interneuron.
- The inhibitory interneuron directly acts upon the postsynaptic membrane of the target neuron. This typically occurs at an axosomatic synapse, where the cell body (soma) of a neuron (e.g., a pyramidal neuron) is targeted.
- The released inhibitory neurotransmitter acts on the postsynaptic membrane.
- An increase in the negative membrane potential occurs — hyperpolarization.
- As a result, the threshold of excitation of the principal neuron increases, and an inhibitory postsynaptic potential (IPSP) develops.
The net outcome of this process is reduced tissue excitability and the inability to generate an action potential.
Which Neurotransmitters Mediate This Process?
Depending on the neurotransmitter released, hyperpolarizing inhibitory neurons are divided into several types:
- Glycinergic neurons — release glycine, mediating postsynaptic inhibition.
- GABAergic neurons — release gamma-aminobutyric acid (GABA). They can mediate both postsynaptic and presynaptic inhibition.
- Mixed-type neurons — co-release both glycine and GABA from the same axon terminals. Such neurons are found predominantly in the brainstem.
What Is the Clinical Significance (Pain Suppression Example)?
Synaptic mechanisms of pain suppression are realized at the spinal level — in the dorsal horn of the spinal cord, where the terminals of primary afferents and interneurons reside.
At the postsynaptic level, hyperpolarization of interneuronal membranes depresses their activity. Combined with presynaptic inhibition, which reduces the release of nociceptive pain transmitters — glutamate, neurokinins, and substance P — this leads to a blockade of pain impulse transmission to higher CNS centers.
What Is Its Place in the Electrophysiological Classification?
In addition to hyperpolarization inhibition, which decreases excitability via inhibitory neurotransmitters, two other membrane mechanisms of inhibition are recognized:
- Persistent depolarization inhibition — occurs during high-frequency stimulation. An excess of excitatory neurotransmitter (known as pessimal inhibition) or a lack of an inactivating enzyme causes sustained activation of sodium and potassium channels. The membrane cannot return to the resting state, extending the absolute refractory period and increasing the difference between the current membrane potential and the critical depolarization threshold. This process is analogous to parabiosis or accommodation. It may also occur under the action of inhibitory neurotransmitters due to specific membrane properties.
- Stabilizing inhibition — occurs under the influence of certain biologically active substances. A blockade of membrane sodium permeability occurs without altering the resting membrane potential, rendering excitation impossible.