Gamma-Aminobutyric Acid

Gamma-Aminobutyric Acid (GABA) is a naturally occurring amino acid that is an inhibitory neurotransmitter in the brain. It has analgesic properties and slows down the brain's response by blocking specific signals in the central nervous system (brain and spinal cord). Disturbances in GABA signalling have been associated with a variety of neurological and psychiatric disorders. Therefore, regulation of GABA signalling is the basis for many pharmacological treatments in neurology, psychiatry and anaesthesiology.

Gamma-Aminobutyric Acid (GABA) is available as a dietary supplement for conditions such as stress, anxiety, depression and hypertension. However, when taken orally, GABA may not cross the blood-brain barrier. Therefore, it is not clear whether GABA supplements have any effect on the brain. In clinical practice, GABA is involved in the treatment of several disease states such as pyridoxine deficiency, hepatic encephalopathy, some Huntington's disease and dystonia or spasticity.

Gamma-Aminobutyric Acid exerts its primary function in synapses between neurons by binding to postsynaptic GABA receptors that regulate ion channels, hyperpolarised cells and inhibit action potential transmission.
GABA is synthesized in the cytoplasm of the presynaptic neuron from the precursor glutamate by the enzyme glutamate decarboxylase, an enzyme which uses vitamin B6 (pyridoxine) as a cofactor. After synthesis, it is loaded into synaptic vesicles by the vesicular inhibitory amino acid transporter. SNARE complexes help dock the vesicles into the plasma membrane of the cell. When an action potential reaches the presynaptic cell, voltage-gated calcium channels open and calcium binds to synaptobrevin, which results in the fusion of the vesicle with the plasma membrane and releases GABA into the synaptic cleft where it can bind with GABA receptors. GABA can then be degraded extracellularly or taken back up into glia or the presynaptic cell. It is degraded by GABA-transaminase into succinate semialdehyde which then enters the citric acid cycle.
GABA binds to two major post-synaptic receptors, the GABA-A and GABA-B receptors. The GABA-A receptor is an ionotropic receptor that increases chloride ion conductance into the cell in the presence of GABA. The extracellular concentration of chloride is normally much higher than the intracellular concentration. Consequently, the influx of negatively charged chloride ions hyperpolarizes the cell, inhibiting the creation of an action potential. The GABA-B receptor functions via a metabotropic G-protein coupled receptor which increases postsynaptic potassium conductance and decreases presynaptic calcium conductance, which consequently hyperpolarizes the postsynaptic cell and prevents the conduction of an action potential in the presynaptic cell. Consequently, regardless of binding to GABA-A or GABA-B receptors, GABA serves an inhibitory function.