GABA transporter 1

GABA Transporter 1

GABA Transporter 1 (GAT1) is a protein that in humans is encoded by the SLC6A1 gene. It is a member of the solute carrier family and plays a crucial role in the nervous system by regulating the levels of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system.

Structure

GAT1 is a transmembrane protein that belongs to the SLC6 family of neurotransmitter transporters. It typically consists of 12 transmembrane domains, with both the N-terminus and C-terminus located intracellularly. The structure of GAT1 is critical for its function in transporting GABA across the cell membrane.

Function

GAT1 is responsible for the reuptake of GABA from the synaptic cleft back into presynaptic neurons and surrounding glial cells. This reuptake process is essential for terminating the inhibitory signal of GABA and for maintaining the balance of excitatory and inhibitory signals in the brain. By regulating GABA levels, GAT1 plays a key role in modulating neurotransmission and maintaining homeostasis in the nervous system.

Mechanism

GAT1 functions as a sodium- and chloride-dependent transporter. It uses the electrochemical gradient of sodium ions across the cell membrane to drive the uptake of GABA into cells. The transport process involves the co-transport of two sodium ions and one chloride ion along with one GABA molecule.

Clinical Significance

Alterations in GAT1 function have been implicated in various neurological and psychiatric disorders. For example, reduced GAT1 activity can lead to increased GABAergic activity, which may contribute to conditions such as epilepsy and anxiety disorders. Conversely, enhanced GAT1 activity may be associated with depression and other mood disorders.

Pharmacology

GAT1 is a target for several pharmacological agents. Inhibitors of GAT1, such as tiagabine, are used clinically to increase GABA levels in the brain and are effective in the treatment of epilepsy. These inhibitors work by blocking the reuptake of GABA, thereby prolonging its action in the synaptic cleft.

Research

Ongoing research is focused on understanding the detailed structure-function relationship of GAT1, its regulation, and its role in various diseases. Advances in crystallography and molecular biology techniques continue to provide insights into the precise mechanisms by which GAT1 operates.

See Also

• GABA receptor
• Neurotransmitter transporters
• SLC6A1 gene