Gamma-Aminobutyric acid, or gamma-aminobutyric acid is the chief inhibitory neurotransmitter in the developmentally mature central nervous system.
Its principal role is reducing neuronal excitability throughout the nervous system.
GABA’s major purpose in the brain is to reduce neuronal excitability and has been clinically used to reduce anxiety, treat attention deficit disorder, and improve mood.
In humans, GABA is also directly responsible for the regulation of muscle tone.
GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neuronal processes.
This binding causes the opening of ion channels to allow the flow of either negatively charged chloride ions into the cell or positively charged potassium ions out of the cell, resulting in a negative change in the transmembrane potential, usually causing hyperpolarization.
Two general classes of GABA receptor are known:
GABAA in which the receptor is part of a ligand-gated ion channel complex.
GABAB metabotropic receptors, which are G protein-coupled receptors that open or close ion channels via G proteins.
Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors.
GABAA receptors are ligand-activated chloride channels: when activated by GABA, they allow the flow of chloride ions across the membrane of the cell.
When net chloride flows out of the cell, GABA is depolarizing.
When chloride flows into the cell, GABA is inhibitory or hyperpolarizing.
When the net flow of chloride is close to zero, the action of GABA is shunting.
Shunting inhibition reduces the effect of any coincident synaptic input by reducing the electrical resistance of the cell’s membrane resulting in overall inhibition even if the membrane potential becomes less negative.
As the brain develops into adulthood, its role changes from excitatory to inhibitory.
It regulates the proliferation of neural progenitor cells the migration and differentiation and the elongation of neurons and the formation of synapses.
Reduced GABA levels have been observed in plasma, CSF, and cortical brain tissues of patients with depression.
It has a role in regulating the growth of embryonic and neural stem cells.
GABA activates the GABAA receptor, causing cell cycle arrest in the S-phase, limiting growth.
Besides the nervous system, GABA is also produced at relatively high levels in the beta-cells of the pancreas.
Ethanol and tranquilizers such as barbiturates and benzodiazepines function as positive allosteric modulators at GABAA receptors.
With DTs the brain triggers the abrupt stopping of the production of endogenous GABA.
This decrease GABA becomes more and more marked as the addiction to alcohol and barbituates becomes stronger and as higher doses are needed to cause intoxication.
GABA has sedative properties, and is an important regulatory neurotransmitter that controls the heart rate, blood pressure, and seizure threshold among myriad other important autonomic nervous subsystems.
The beta-cells secrete GABA along with insulin and the GABA binds to GABA receptors on the neighboring islet beta-cells.
GABA inhibits gamma-cells from secreting glucagon, which counteract insulin’s effects.
GABA can promotes the replication and survival of beta-cells and also promotes the conversion of beta-cells.
It has been detected in other peripheral tissues including intestines, stomach, Fallopian tubes, uterus, ovaries, testes, kidneys, urinary bladder, the lungs and liver, albeit at much lower levels than in neurons or beta-cells.
GABAergic activities have been demonstrated in various peripheral tissues and organs, which include the intestines, the stomach, the pancreas, the Fallopian tubes, the uterus, the ovaries, the testes, the kidneys, the urinary bladder, the lungs, and the liver.
Immune cells express receptors for GABA and administration of GABA can suppress inflammatory immune responses and promote immune responses.
GABA has shown to regulate secretion of a number of cytokines.
GABA is found mostly as a zwitterion.
GABAergic neurons which produce GABA is synthesized from glutamate via the enzyme glutamate decarboxylase (GAD) with pyridoxal phosphate (the active form of vitamin B6) as a cofactor.
The principal excitatory neurotransmitter glutamate is converted into GABA, the principal inhibitory neurotransmitter.
Exogenous GABA in the form of nutritional supplements could exert GABAergic effects on the enteric nervous system which in turn stimulate endogenous GABA production.
Both glutamate and glutamine can freely cross the blood brain barrier and convert to GABA within the brain.
Drugs that act as modulators of GABA receptors are known as GABA analogues or GABAergic drugs.
Modulators of GABA receptors are known as GABA analogues or GABAergic drugs increase the available amount of GABA, and typically have relaxing, anti-anxiety, and anti-convulsive effects.
Many GABA analogues or GABAergic drugs are known to cause anterograde amnesia and retrograde amnesia.
In general, GABA does not cross the blood-brain barrier.
Some areas of the brain that have no effective blood-brain barrier, such as the periventricular nucleus, can be reached by drugs such as systemically injected GABA.
It is suspected that GABA is involved in the synthesis of melatonin and thus might exert regulatory effects on sleep and reproductive functions.
GABA is sold as a dietary supplement.
Has 19 subunit variants, each encoded by different genes.
Divided into 8 classes.
Gamma 1 subunit responsible for sedative, amnestic and anticonvulsive properties of benzodiazepines.
Gamma 2 subunits responsible for anxiolytic effects.
Autoantibodies against amphiphysin and gephyrin are also sometimes found in stiff person syndrome patients, which interact with antigens in the brain neurons and the spinal cord synapses, causing a functional blockade of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).