Neuroscience Basics: GABA Receptors and GABA Drugs, Animation

Author: Alila Medical Media

Gamma-aminobutyric acid, or GABA, is the primary INHIBITORY neurotransmitter in the mature brain. It REDUCES neuronal activity of target cells through its binding to GABA receptors present on the cell surface. Nearly half of all synapses of the brain express some kind of GABA receptor and are thus responsive to GABA.

There are at least 3 types of GABA receptors: GABA-A, GABA-B and GABA-C. GABA-A and GABA-C are ligand-gated chloride channels. Upon transmitter binding, they open and allow chloride ions to flow into the neuron, making it more NEGATIVE, or HYPER-polarized, and thus LESS likely to generate action potentials. GABA-B acts through a G-protein to activate potassium channels, which allow positively-charged potassium to flow OUT of the cell, again resulting in membrane HYPER-polarization and a subsequent decrease in neuron responsiveness. GABA is believed to play a major role in controlling neuronal hyperactivity associated with fear, anxiety and convulsions.

GABA-A receptor is composed of 5 protein subunits. In addition to binding sites for GABA, it has allosteric binding sites for other substances known as GABA modulators. These are molecules that can INCREASE or DECREASE the action of GABA, but have no effect in the absence of GABA. For example, benzodiazepines, a class of drugs used to treat anxiety, bind to GABA-A receptor and facilitate its binding to GABA, thus potentiating GABA inhibitory effect.

Other positive modulators include barbiturates, alcohol, propofol, among others. Examples of negative modulators are convulsants, such as Flumazenil. Flumazenil reverses the effects of benzodiazepines by competing with them at the same binding site on GABA-A.

Neuroscience Basics: GABA Receptors and GABA Drugs, Animation

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