Three subtypes of GABA receptors have been identified: GABAA , GABAB , and GABAC (Table 1). The GABAA and GABAB receptors (Figure 1) are widely distributed in the CNS, whereas in adult vertebrates the GABAC receptors are found almost exclusively in the retina. The GABAA and GABAC receptors are examples of ionotropic receptors, activation of which allows the entry of Cl– into neurons to mediate fast inhibitory postsynaptic potentials (IPSP). The GABAB receptors are examples of GPCR that are linked via G-proteins to alter the influx of K+ and Ca2+; Gi inhibits adenylyl cyclase to open a K+ channel, and Go inhibits or delays Ca2+ influx. Activation of GABAB receptors mediates both presynaptic and slow postsynaptic inhibition.
Table1. Pharmacology of a selection of receptors for some small-molecule neurotransmitters.
Fig1. Diagram of GABAA and GABAB receptors, showing their principal actions. Two molecules of GABA (squares) bind to the GABAA receptor to allow an influx of Cl- to mediate fast inhibitory postsynaptic potentials. One molecule of GABA binds to the GABAB receptor, which couples to the α-subunit of a G-protein; Gi inhibits adenylyl cyclase to open a K+ channel and Go inhibits Ca2+ influx.
The GABAA receptors are pentamers made up of various combinations of six α subunits, four β, four γ, one δ, and one ε. This endows them with considerably different properties from one location to another. However, most synaptic GABAA receptors have two α, two β, and one γ subunit (Figure 1). GABAA receptors on dendrites, axons, or somas often contain δ and ε subunits in place of the γ subunit. The GABAC receptors are relatively simple in that they are pentamers of three ρ subunits in various combinations.
