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What are the Different Types of GABA Receptor?

By Greg Caramenico
Updated Jan 31, 2024
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GABA, or gamma-aminobutyric acid, is the major inhibitory neurotransmitter in mammals' brains. GABA receptors are the most common single receptor found in the synapses where neurons communicate with each other. There are two known types of GABA receptor: GABA-A, which comprise the primary sites of sedative drug action, and GABA-B, which play a role in muscle tone regulation. The effects of common substances like alcohol and anesthetics are modulated by the A-type GABA receptor.

GABA-A receptors are ionotropic, which means that they function as ion channels. They are in the cell membrane in neuronal axons, where they synapse with other neurons. When GABA is released into the synapse from a neuron, it binds to the receptor on the adjacent dendrite, allowing ions into the cell and causing the neuron to be less electrically excitable. This inhibits the neuron from firing. While there are many excitatory types of receptors, GABA is the primary inhibitory neurotransmitter.

The types of GABA receptors can be sorted according to how molecules bind to them and whether these activate or deactivate the receptor. Activating compounds mimic the action of GABA and are called agonists, whereas those that bind the receptor but do not do anything are known as antagonists. With GABA-A, there is a third class of activating compounds, called allosteric modulators, that include the barbiturates and many anesthetics. GABA-A agonists range from the hallucinogen muscimol, found in certain wild mushrooms, to zolpidem, the active ingredient in many anti-insomnia drugs.

Drugs like benzodiazepines and barbiturates interact with the brain at the GABA-A receptor. While all these drugs inhibit neuronal firing, their specific action varies with dosage. Mild doses will reduce anxiety and calm neuromuscular activity, and large doses induce sleep or anesthesia, but an overdose can be fatal. The effects of alcohol on the central nervous system derive from the ethanol molecule binding to the GABA receptor, triggering widespread sedation and relaxation. There is a subtype of the GABA-A receptors called GABA-a-rho, which does not respond to many of these drugs.

The GABA-B receptor is not as fully understood as the A GABA receptor. It is metabotropic, which means that it operates through a series of chemical messengers that change its structure when activated. GABA-B prevents sodium channels from opening, inhibiting neuronal firing. The GABA-B receptor is found in the spinal cord and in nerves in the peripheral nervous system, where its activation regulates muscular activity through inhibitory control. It is a possible target of some muscle relaxants and many compounds used to test the effects of GABA in laboratory animals.

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