Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs

Controlling Epileptiform Activity with Organic Electronic Ion Pumps

“…[24,25] It is also particularly relevant in the context of epilepsy since many antiepileptic drugs have been designed to boost GABAergic neurotransmission. [26,27] OEIPs can be used to deliver ions and small charged molecules, such as neurotransmitters, with high spatial resolution, to stimulate cell activity locally. [50,51] The OEIP key component is a cation exchange membrane (CEM), a polyanion, which, because of its high concentration of fixed negative charges, is selectively permeable to cations.…”

High Selectivity of the γ-Aminobutyric Acid Transporter 2 (GAT-2, SLC6A13) Revealed by Structure-based Approach

“…GABAergic Signaling and the GABA Transporters-GABA is a key inhibitory neurotransmitter in the mammalian brain and acts by binding to the GABAergic receptors in inhibitory neurons (e.g., GABA A ) in the CNS (4). GABAergic mechanisms have also been found in the stomach, pancreas, intestine, testis, ovary, uterus, liver, urinary bladder, and kidney (5).…”

“…Malfunctions of the GABAergic system have been associated with mucous overproduction in asthma (6), as well as with protective and regenerative effects on islet ␤ cells in diabetes (7). The GABA transporter (GAT) family consists of four transporters that regulate the concentration of GABA available for signaling via the GABAergic receptors (4,8). Therefore, the GATs are emerging drug targets for a variety of disorders, primarily those that have been associated with neurosignaling (4).…”

“…The GABA transporter (GAT) family consists of four transporters that regulate the concentration of GABA available for signaling via the GABAergic receptors (4,8). Therefore, the GATs are emerging drug targets for a variety of disorders, primarily those that have been associated with neurosignaling (4). For example, GAT-1 (SLC6A1) and GAT-3 (SLC6A11) are key targets for anticonvulsants and relaxants (e.g., tiagabine (Gabitril)).…”

Ligand-gated Ion Channels

“…GAT3 resides predominantly on distal astrocytic terminals that are close to the GABAergic synapse. By contrast, BGT1 occupies an extrasynaptic location possibly along with GAT2 which has limited expression in the brain (Madsen et al, 2010). TauT is a high affinity taurine transporter involved in osmotic balance that occurs in the brain and non-neuronal tissues, such as the kidney, brush border membrane of the intestine and blood brain barrier Han et al, 2006).…”