Figure 1.

Partial or complete loss of GABA reuptake activity is a common phenomenon across GABA transporter 1 (encoded by SLC6A1) variations associated with a wide spectrum of epilepsy syndromes and neurodevelopmental disorders. (A) Schematic presentation of variant GABA transporter 1 (GAT-1) protein topology and locations of variations in human SLC6A1 associated with various epilepsy syndromes and neurodevelopmental disorders. These variations are distributed in various locations and domains of the encoded GAT-1 protein peptide. The coloured dots represent the relative locations of the disease-related variations. ^#Previously reported variants. (B and C) HEK293T cells were transfected with the empty vector pcDNA, wild-type, or the variant GAT-1^YFP for 48 h. The graphs represent the altered GABA reuptake function of the variant GAT-1 encoded by 22 different SLC6A1 variations in HEK293T cells measured by the high-throughput ³H radiolabelling GABA uptake on a liquid scintillator with QuantaSmart. ‘966’ indicates the wild-type treated with GAT-1 inhibitor Cl-966 (50 µM), and ‘NNC-711’ indicates the wild-type treated with NNC-711 (70 µM) for 30 min before preincubation. n = 4 different transfections, ^§§§P < 0.001 overall variations versus wild-type, *P < 0.05, **P < 0.01, ***P < 0.001 versus wild-type, one-way ANOVA and Newman-Keuls test. Values are expressed as mean ± SEM.