Gamma-aminobutyric acid

Gamma-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a principal role in reducing neuronal excitability throughout the nervous system. GABA is sold as a dietary supplement in many countries. It is also used as a medication, primarily for the treatment of anxiety.

Structure and Function

GABA is a amino acid that functions as a neurotransmitter in the central nervous system. Its primary role is to inhibit nerve transmission in the brain, calming nervous activity. This can be seen in the regulation of muscle tone and normal brain function.

Biosynthesis

GABA is synthesized directly from the amino acid glutamate using the enzyme glutamate decarboxylase (GAD) and pyridoxal phosphate (the active form of Vitamin B6) as a cofactor. This process converts glutamate, the principal excitatory neurotransmitter, into GABA.

Function

In the human brain, 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. This action results in a negative change in the transmembrane potential, usually causing hyperpolarization.

Pharmacology

GABA's role as an inhibitory neurotransmitter has made it a primary target for drugs that affect neuronal transmission. Many sedatives and anxiolytics directly enhance the effects of GABA by increasing GABA affinity for its receptor. Benzodiazepines, for example, bind to a specific site on the GABA_A receptor, increasing the amount of time the ion channels remain open, thus enhancing the inhibitory effects of GABA. Other substances, like barbiturates, increase the duration of the chloride ion channel openings, thereby making the drugs potent inhibitors of neuron firing.

Clinical Significance

Alterations in GABA neurotransmitter systems have been implicated in the pathogenesis of various neurological and psychiatric disorders, including epilepsy, anxiety disorders, and schizophrenia. GABAergic mechanisms are also targets for various therapeutic agents.

See Also

• Neurotransmitter
• Inhibitory postsynaptic potential
• Excitatory neurotransmitter
• Nervous system