GABA transporter

GABA transporters (

SLC6) family.^[1]^[2] They are found in various regions of the brain in different cell types, such as neurons and astrocytes

.

These transporters are primarily responsible for the regulation of extracellular GABA concentration during basal and synaptic activity. They are responsible for creating a GABA gradient which is determined by the

plasma membrane of neurons and glia which help define their function of regulation of GABA concentration as they act as the receptors that facilitate recycling of GABA in the extracellular space.^[1] GABA transporters are a common target for anticonvulsant drugs against seizure disorders such as epilepsy.^[3]

Types

Molecular phylogenetic analysis of the SLC6 neurotransmitter transporter family in *Homo sapiens*

The GABA transporter group consists of six different transporters:

SLC6A1
)
GABA transporter type 2 (GAT2; SLC6A13)
GABA transporter type 3 (GAT3; SLC6A11)
SLC6A12
)
SLC6A8
)
SLC6A6
)

GAT1 and GAT3 are the major GABA transporters in the brain and spinal cord, expressed by both neurons and some astrocytes.^[4] GAT2 and BGT1 are also expressed in the brain, but at low levels and mostly in the meninges. GAT2 also transports taurine, while BGT1 transports betaine. These two transporters are predominantly expressed in the liver, but are also found in the kidneys and, as mentioned above, in the meninges.^[4]

Function

The cartoon depicts a GABAergic synapse in adult rat brain where GABA is released exocytotically and acts upon specific post-synaptic receptors. The signal is terminated by removal of GABA from the synaptic cleft by transport of GABA back into the nerve terminal by the plasma membrane GABA transporter (GAT) 1.

GABA transporters in the plasma membrane help in regulating the concentration of GABA in the

electrogenic, a voltage-dependent which relies on the inward electrochemical gradient of Na+ ions instead of ATP.^[5] It also has low micromolecular affinity to GABA with a Michaelis-Menten constant of 2.5 μM,^[1] and requires the presence of Cl- ions in the extracellular matrix. The GABA transporter help creates an equilibrium of GABA and will work in the reverse direction if needed to maintain the baseline concentration of GABA in the system.^[1]

Structure

The structure of Sl6 family transporters share 20-25% sequence similarity with LeuTA [6] providing an evolutionary relationship between the transporter and the leucine transporter protein.^[2] Because of the similarity, the LeuTa protein provides a very close template model for the studying the transporters in greater detail.^[1] The GABA transporter exists in two different conformations. The transporters have general structure of 12 alpha helices with both end - N Terminus and C-terminus in the cytoplasm with glycosylation sequence in the transmembrane helices.^[7] They also exhibit ligand gated ion channel properties as well as substrate dependent properties of leak current. The amino acid sequence ranges from 599 (GAT1) to 700 for glycine transporters.^[5]

Role in epilepsy

GABA creates an inhibitory tone in the

temporal lobe seizures, there is a decrease in GABA release because of the impairment of transporters. Drugs such as Vigabatrin cause reversals in GABA transporters that increase the concentration of GABA in the synapse which helps in inhibiting the neuronal excitability.^[3]