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GAT1 - "Electrophysiological recordings of hGAT1 (SLC6A1) activity on Nanion’s SURFE²R N1"

Icon N1   SURFE²R application note  logo pdf   (0.4 MB)

Summary:

GABA is the major inhibitory neurotransmitter in the brain and is important in controlling excitability. After release, GABA is removed from the extracellular space by GABA transporters (GATs), thus terminating inhibitory synaptic transmission. The GABA transporters belong to the family of neurotransmitter:sodium symporters referred to as the solute carrier 6 (SLC6) family in humans. GATs co-transport GABA, Na+ and Cl- with the proposed stiochiometry 1 GABA: 2 Na+: 1 Cl-, resulting in a net influx of 1 positive charge per cycle. So far, 4 GATs have been identified, GAT1, GAT2, GAT3 and BGT1.

GAT1 is expressed throughout the brain in both GABAergic and non-GABAergic neurons, and is expressed in particularly high levels in the olfactory bulb, basal ganglia, cerebellum and retina. The physiological function of GAT1 is primarily to terminate synaptic transmission but also to ensure the fidelity of synaptic transmission by preventing the spread of neurotransmitter to neighbouring synapses. GABA transporters also play an important role in neurotransmitter reutilization. In certain circumstances, e.g. when the sodium gradient increases during ischemia or following seizures, GATs can act in reverse which may have a protective effect during seizures, by inhibiting electrical excitability. There is some evidence that GATs may play a role in neurodegenerative diseases such as Parkinson’s and Alzheimer’s and may provide a novel target for treating these conditions.

Here we present human GAT1 activity measurements on the SURFE2R N1 instrument using purified plasma membranes from HEK cells. GABA affinity and effect of inhibitors were investigated.

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