An ionotropic receptor is a type of neurotransmitter receptor that consists of a neurotransmitter binding site and an ion channel. They are ligand-gated ion channels made of three, four, or five protein subunits. Together they form an ion-conducting pore in the middle of the neuron cell’s receptor.
This type of receptors can be modulated by a range of endogenous substances. Due to this, they are often targets for therapeutic compounds.
What Are Receptors in the Brain?
A receptor is a protein or a group of several proteins located in the membrane of a neuron cell that a molecule (such as a neurotransmitter, hormone, or drug) can bind to.
What Are Neurotransmitters?
Neurotransmitters are chemical molecules (messengers) in the central nervous system that relay the nerve impulse when nerve cells, or neurons, are stimulated. When that happens, they undergo chemical changes that produce tiny waves of electricity, i.e. electrical nerve impulses.
How Do Receptors Communicate With the Brain?
When a brain cell receives a sensory signal from our senses, it fires an electrical impulse. This impulse that carries the information travels down the axon in order to reach the axon terminal where the neurotransmitters are stored.
After the signal reaches its targeted location (of the neuron cell), the chemical messenger binds to the receptor of a neighboring cell and completes the relay of its message.
What Is the Main Function of the Ionotropic Receptor?
The main function of the ionotropic receptors is to convert the extracellular chemical signals into electrical information.
These receptors are of vital importance for the synaptic relay of sensory information gained from the sensory organs of the body, as well as for the other forms of signaling between various types of neuron cells in the brain.
What Is the Structure of the Ionotropic Receptor?
An ionotropic receptor forms two functional domains: an extracellular site that binds the neurotransmitters, and a membrane where the ion channel is formed.
These receptors are often made of several sub-units. When the ligand binds to one or more sub-units, it results in a conformational change of the neuron cell structure that opens the ion channels.
What Are the Types of Ionotropic Receptors?
Ion channels, i.e. ionotropic receptors are membrane proteins that play the main role in the regulation of cellular excitability. They are activated only in the immediate region of the receptor.
What Are the Types of Ion Channels?
Ionotropic receptors are found in almost all neuron cells of the brain and carry crucial physiological importance. Based on the type of sensory stimuli to which they respond, ion channels are divided into three superfamilies:
- Voltage-gated ion channels;
- Ligand-gated ion channels;
- Mechano-sensitive ion channels.
Voltage-gated Ion Channels
Voltage-gated ion channels are highly selective of a specific ion, i.e., K+, Ca2+, Na+, and Cl-. Based upon the major permeant ion, they can be divided into:
- Voltage-gated Na+ channels – These ion channels are responsible for the production of long-lasting action potentials in the neurons. Due to this, they are targets of local anesthetics, such as lidocaine and benzocaine.
- Voltage-gated K+ channels – The K+ channels constitute the largest and the most diverse family of voltage-gated ion channels. They are responsible for generating the resting membrane potential.
- Voltage-gated Cl- channels – Every type of neuron cell has a voltage-gated Cl- channel because they regulate both the excitability and the cell volume. These channels also contribute to the resting membrane potential.
- Voltage-gated Ca2+ channels – This type of ion channels regulate the Ca2+ concentrations in the neuron cell and are involved in a wide range of biochemical processes within the cells.
Ligand-gated Ion Channels
Drugs such as anesthetics, antipsychotics, and antidepressants, target the ligand-gated ion channels. These channels are named after the ligand to which they respond:
- Cys-loop ligand-gated ion channels
- Ionotropic glutamate receptors
- P2X Receptors
Mechano-sensitive Ion Channels
These channels participate in both the detection and process of converting external mechanical forces into electrical and/or chemical signals that are relayed between the neuron cells.
The ion channels, sensitive to mechanical forces, are involved in the regulation of blood pressure and volume of the neuron cells, the stimulation of muscle and bone development, as well as the senses of touch and hearing.
What Are the Families of Ionotropic Receptors?
There are several families of ionotropic receptors, which differ in their molecular structure and the ligands that open them:
- Cys-loop receptors
- Anionic Cys-loop receptors
- Cationic Cys-loop receptors
- Ionotropic glutamate receptors
- AMPA receptor
- NMDA receptors
- GABA receptors
- 5-HT3 receptor
What Are Cys-loop Receptors?
Cys-loop receptors have a distinguished function in the nervous system. They are comprised of the following structures:
- γ-aminobutyric acid type A receptors,
- nicotinic acetylcholine receptors,
- 5-hydroxytryptamine type-3 receptors,
- glycine receptors.
What Are the Types of Cys-loop Receptors?
The Cys-loop receptors are subdivided with respect to the type of ion that they conduct into:
- Nicotinic acetylcholine receptors,
- GABAA,
- GABAA-ρ,
- Glycine receptors,
- Serotonin 5-HT3 receptors.
GABA Receptors
GABA receptors are located in the limbic system, a brain area dedicated to the control and regulation of personal feelings and the storing of emotional memories.
Gamma-aminobutyric acid or GABA is the most powerful inhibitory neurotransmitter. Its natural function is to reduce the activity of the neuron cells to which it binds.
When GABA attaches to a GABA receptor in the brain, it produces a calming effect. Namely, the GABA receptors located on the nerve cells receive the chemical impulses that support the inhibition or reduction of the nerve impulses.
This reduction of the neuronal excitability throughout the nervous system supports the control and regulation of stress and fear.
In addition, GABA is most commonly used in the treatment of anxiety, high blood pressure, insomnia, fatigue, etc. It is also used for burning fat, stabilizing blood pressure, and relieving pain.
What Are the Types of GABA Receptors?
There are two main types of GABA receptors – the ionotropic GABAA receptor (ligand-gated ion channels), and the metabotropic GABAB receptor (G protein-coupled receptors).
In the adult brain, the GABA receptor acts primarily through activation of the fast hyperpolarizing GABAA receptors. While the GABAA receptor reduces the neuronal excitability, the GABAB receptor leads to a decreased cyclic adenosine monophosphate (cAMP).
Nicotinic Acetylcholine Receptors
The nicotinic acetylcholine receptors are located in the neuromuscular junction. Permeable to sodium, potassium, and calcium ions, they form ligand-gated ion channels in the plasma membranes of certain neurons, as well as on the postsynaptic side of the neuromuscular junction.
When the acetylcholine binds to them, they switch from closed to open. While open, they give way to the ions that pass through. These excitatory receptors are responsible for the contraction of the skeletal muscles.
Which Are the Nicotinic Agonists?
Nicotinic acetylcholine receptor agonists are drugs that bind to and activate the nicotinic cholinergic receptors. The list of nicotinic acetylcholine receptor agonists includes the following drugs:
- Nicotine – This is a stimulatory alkaloid found in tobacco products. It’s often administered in the therapy for nicotine withdrawal symptom relief. As such, it aids the process of smoking cessation.
- Varenicline – A partial agonist at nicotinic acetylcholine receptors used as support in smoking cessation therapy.
- Encenicline – Cognition, schizophrenia, Alzheimer’s Disease, and central nervous system diseases are some of the targeted neurological conditions treated with encenicline.
- Lobeline – Alzheimer’s disease, schizophrenia, as well as the schizoaffective disorders are best treated by this drug that binds to the nicotinic acetylcholine receptors.
Glutamate Receptors
Glutamate receptors are the most numerous excitatory receptors in the central nervous system of the brain. Their activation triggers the basal excitatory synaptic transmission, as well as many forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD).
Several types of ionotropic glutamate receptors have been identified so far. The list of the most significant ones includes:
- The ligand-gated ion channels called NMDA receptors,
- The AMPA receptors,
- The kainate receptors.
What Is the Function of Glutamate?
The neurotransmitter glutamate is found in both the brain and the spinal cord. This powerful neurotransmitter supports the transmission of signals between neuron cells. It also plays a vital function in the early development of the brain, in the cognitive processes (especially learning), perception, as well as memory.
Serotonin 5-HT3 Receptors
The serotonin 5-HT3 receptor is a cation-selective ion channel capable of conducting fast excitatory neurotransmission in both the central nervous system and the peripheral nervous system.
Serotonin is a neurotransmitter hormone that is responsible for the transmission of information among neurons of the brain. It supports the cognitive processes as well as the formation of memory.
Fun Facts
Did you know?
- Nicotine is also present in potatoes, tomatoes, and eggplants in small concentrations.
- Benzodiazepines (sedatives) are a class of psychoactive drugs that bind to the same receptors as GABA and mimic GABA’s natural calming effects. They increase the effect of the gamma-aminobutyric acid (GABA) at the GABAA receptor in order to decrease the excitability of neurons.
- Neurotransmitters can be classified into 2 main groups: small molecule neurotransmitters and neuropeptides.
- When we have a dysfunctional GABA system in our brain, it can lead to anxiety and feelings of panic, stress, restlessness, or irritability; a decreased tolerance for pain; a fast heart rate; high blood pressure; insomnia; and occasionally seizures.
- Conditionally essential amino acids (neurotransmitters) are needed when the body fights stress or illness.
- The GABA neurotransmitter is synthesized from glutamate – the most powerful excitatory neurotransmitter of the central nervous system. It’s secreted by the neurons located in the sensory pathways of the central nervous system and the cerebral cortex.
- Even though nicotine triggers tobacco addiction, it’s also used in therapy for quitting cigarettes.
- When the concentration of glutamate is too small, it can lead to coma, psychosis, or even death. On the other hand, an extremely high concentration of this neurotransmitter can cause seizures and brain cell death.
- Long-term potentiation (LTP) and long-term depression (LTD) are mechanisms that are believed to support learning and memory.
- Nicotine reaches the brain in less than 10 seconds when inhaled!