GABA receptor

It has long been recognized that, for neurons that are stimulated by bicuculline and picrotoxin, the fast inhibitory response to GABA is due to direct activation of an anion channel.

In addition, activation of GABA receptors lead to the so-called shunting inhibition, which reduces the excitability of the cell independent of the changes in membrane potential.

According to the excitatory GABA theory, this phenomenon is due to increased intracellular concentration of Cl¯ ions either during development of the nervous system[12][13] or in certain cell populations.

However, the excitatory GABA theory has been questioned as potentially being an artefact of experimental conditions, with most data acquired in in-vitro brain slice experiments susceptible to un-physiological milieu such as deficient energy metabolism and neuronal damage.

[30][31] Native responses of the GABAC receptor type occur in retinal bipolar or horizontal cells across vertebrate species.

[41] A slow response to GABA is mediated by GABAB receptors,[42] originally defined on the basis of pharmacological properties.

This ability of GABA to inhibit neurotransmitter release from these preparations was not blocked by bicuculline, was not mimicked by isoguvacine, and was not dependent on Cl¯, all of which are characteristic of the GABAA receptor.

Later ligand-binding studies provided direct evidence of binding sites for baclofen on central neuronal membranes.

One significant example of a deleterious mutation is the major association between several GABA receptor gene polymorphisms and schizophrenia.