What is GABA?

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When reading about alcohol or benzodiazepines (benzos) you often come across the term GABA. In this article, we’ll explain what exactly GABA is.

GABA receptors, a group of receptors that responds to neurotransmitter Gamma-aminobutyric Acid (GABA), are the main inhibitory compound in the mature vertebrate central nervous system. GABAA receptors are different from GABAB. GABAA receptors can be ligand-gated, ion channel receptors (also called ionotropic or ionotropic receptors), whereas GABAB receptors can be G protein-coupled receptors.

For a long time, it has been known that neurons that respond quickly to GABA when stimulated with picrotoxin and bicuculline are due to direct activation via an anion channel. The GABAA receptor was named after this channel. GABA receptors that respond quickly are part of the Cys-loop family of Cys-loop-ligand-gated Ion channels. This superfamily includes GABAA receptors and nicotinic acetylcholine receivers.

GABAA receptors that are ionotropic trigger the opening of a chloride-selective porous. GABA molecules bound to their binding sites in extracellular receptors activate an ionotropic GABAA receptor. An increase in chloride conductance causes the membrane potential to shift towards the Cl-ion reversal potential. This is approximately -75mV in neurons and inhibits the firing of new actions potentials. This is what causes the sedative effects that GABAA allosteric antagonists have. A second mechanism that activates GABA receptors is called shunting inhibition. This reduces excitability independent of changes in membrane potential. Numerous reports have reported excitatory GABAA-receptors. Excitatory GABA theory states that this phenomenon can be attributed to an increased intracellular Cl- ions concentration during nervous system development or in certain cell types. A chloride pump is activated and inserted into cells membranes to pump Cl-ions into extracellular spaces. Inhibitory responses are then produced by further openings due to GABA binding to this receptor. Over-excitation of the receptor causes receptor remodeling and eventually invagination. GABA binding is then inhibited further and inhibitory postsynaptic pots become irrelevant

The excitatory GABA theory is being questioned because it may be an artifact of experimental conditions. Data from in-vitro brain slices experiments are susceptible to un-physiological environments such as neuronal injury and deficient energy metabolism. Numerous studies showed that GABA in neonatal brain slices was inhibited by glucose in the perfusate. This could be because of neuronal damage. These results were questioned by proponents and originators of the excitatory GABA hypothesis. However, the truth was not revealed until GABA’s true effects could be confirmed in an intact human brain. Since then, using technology such as in-vivo electrophysiology/imaging and optogenetics, two in-vivo studies have reported the effect of GABA on the neonatal brain, and both have shown that GABA is indeed overall inhibitory, with its activation in the developing rodent brain not resulting in network activation, and instead of leading to a decrease of activity.

GABA receptors affect neural function by coordinating glutamatergic processes with them.

GABAS receptor has given the designation of a subclass of GABAA receptors that are insensitive to GABAA channels allosteric modulators such as barbiturates and benzodiazepines. The native responses to the GABAC receptor type are found in retinal bipolar and horizontal cells of all vertebrate species.

GABAS receptors only contain r (rho), subunits that are closely related to GABAA subunits. GABAS receptor is often used. However, GABAS could be considered a variant of the GABAA family. Others argue that there are too many differences between GABAS receptors and GABAA receptors to warrant separating these two subclasses. GABAS receptors are very similar in structure, sequence, and function to GABAA ones. Other GABAA receptors, besides those with r subunits, appear to exhibit GABAS behavior. The Nomenclature Committee of IUPHAR recommended that GABAS be dropped and these r receptors are designated the GABAA-r subfamily.

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