GABA receptors play a crucial role in the brain. There are two types of ionotropic receptors, GABAA and GABAC, which are encoded by different sets of genes. Similar to glycine receptors, both GABAA and GABAC receptors control a Cl− channel. GABAA receptors are made up of seven classes of subunits, with three classes having multiple members. The most common configuration is α1, β2, γ2 in a 2:2:1 stoichiometry, accounting for approximately 80% of the receptors. However, there are many other variations of heteromers found in the brain. Different subunits confer distinct properties on the GABAA receptor. For instance, benzodiazepines and barbiturates, two major classes of drugs, target GABAA receptors. Benzodiazepines, such as diazepam, are widely used as antianxiety and relaxant drugs, while barbiturates are used as sedatives and anticonvulsants. Both classes of drugs bind to specific sites on the α subunits of GABAA receptors, enhancing the opening of Cl− channels in response to GABA. The sedative and anticonvulsant effects of benzodiazepines are believed to be mediated by receptors containing the α1 subunit, while the anxiolytic effects are associated with receptors containing the α2 subunit. GABAC receptors are structurally similar to GABAA receptors but have distinct pharmacological characteristics and are encoded by a separate set of genes (ρ1, ρ2, and ρ3).

On the other hand, GABAB receptors are metabotropic receptors. When GABA binds to the GABAB receptor, it activates a heterotrimeric GTP-binding protein (G protein), leading to the activation of K+ channels. This, in turn, hyperpolarizes the postsynaptic cell and inhibits Ca++ channels when located presynaptically, resulting in reduced transmitter release.

Glutamate, another important neurotransmitter, acts on both ionotropic and metabotropic receptors. Based on their pharmacological properties and subunit composition, several distinct ionotropic receptor subtypes are recognized: AMPA, kainate, and NMDA. There are a total of 18 known genes that code for glutamate subunits for the ionotropic glutamate receptors. These genes are divided into different families (AMPA, kainate, NMDA, and δ), which correspond to the different pharmacological subtypes of receptors. Each glutamate receptor is composed of four subunits, and the genes determine the specific receptor type formed. For example, AMPA receptors are formed from GluR1 to GluR4 subunits, kainate receptors require either KA1 or KA2 and GluR5 to GluR7 subunits, and NMDA receptors consist of NR1 subunits in combination with NR2 and NR3 subunits. The properties of ionotropic glutamate receptors vary depending on the subunit composition. These receptors are excitatory and have a cation-selective channel. While all the channels are permeable to Na+ and K+, only a subset allows the passage of Ca++.
GABA has two separate ionotropic receptors (GABAA and GABAC) coded for by distinct sets of genes. Like glycine receptors, both control a Cl− channel. GABAA receptors are heteromers generated from seven classes of subunits, three of which have multiple members. The most common configuration is α1, β2, γ2 in a 2:2:1 stoichiometry, which may account for 80% of the receptors; however, many other heteromers are found in the brain. As with glycine, different subunits confer distinct properties on the receptor. For example, GABAA receptors are the targets of two major classes of drugs: benzodiazepines and barbiturates. Benzodiazepines (e.g., diazepam) are widely used antianxiety and relaxant drugs. Barbiturates are used as sedatives and anticonvulsants. Both classes of drugs bind to distinct sites on the α subunits of GABAA receptors and enhance opening of the receptors’ Cl− channels in response to GABA. The sedative and anticonvulsant actions of benzodiazepines appear to be mediated by receptors with the α1 subunit, whereas the anxiolytic effects reflect binding to receptors with the α2 subunit. GABAC receptors are structurally similar to GABAA receptors but have a distinct pharmacological profile (e.g., they are not affected by benzodiazepines) and are coded for by a separate set of genes (ρ1, ρ2, and ρ3).
The GABAB receptor is a metabotropic receptor. Binding of GABA to this receptor activates a heterotrimeric GTP-binding protein (G protein; see ), which leads to activation of K+ channels and hence hyperpolarization of the postsynaptic cell, as well as inhibition of Ca++ channels (when located presynaptically) and thus a reduction in release of transmitter.
Excitatory Amino Acid Receptors: Glutamate
Glutamate has both ionotropic and metabotropic receptors. Based on pharmacological properties and subunit composition, several distinct ionotropic receptor subtypes are recognized: AMPA, kainate, and NMDA. Overall, there are 18 known genes that code for glutamate subunits for the ionotropic glutamate receptors. The genes are divided into several families (AMPA, kainate, NMDA, and δ) that essentially correspond to the pharmacological subtypes of receptors. Each glutamate receptor is a tetramer. Thus, there is a certain correspondence between the genes and the receptor types that are formed. For example, AMPA receptors are formed from GluR1 to GluR4 subunits, kainate receptors require either KA1 or KA2 and GluR5 to GluR7 subunits, and NMDA receptors all have NR1 subunits plus some combination of NR2 and NR3 subunits. As was mentioned for the other receptors, the receptor properties vary with subunit composition. Ionotropic glutamate receptors are excitatory and contain a cationic-selective channel. Thus, all the channels are permeable to Na+ and K+ , but only a subset allow Ca++ to pass.