Topic: GABA uptake

Adenosine, through the A1 receptor (A1R), is an endogenous anticonvulsant. Development of adenosine receptor agonists as antiseizure drugs has been hampered by cardiac effects. A moderately A1R-selective agonist, MRS5474, has been reported to suppress seizures without appreciable cardiac action (Tosh et al., 2012, J Med Chem, 55:8075). We aimed at understanding its mechanism of action. MRS5474 (50-500nM) was devoid of effect upon rodent excitatory synaptic signals in hippocampal slices, except when hyperexcitability was previously induced in vivo or ex vivo. This contrasted with the effect of

The human γ-aminobutyric acid (GABA) transporter 1 (hGAT-1) is responsible for clearing GABA from synapse into neurons and astrocytes.Its mutations are known to impair protein folding and trigger epilepsy.Such folding defects are amenable to rescue by chemical and pharmacological chaperones.Our aim is to elucidate molecular features of two novel disease variants, in HEK293 cells (in vitro) and Drosophila melanogaster (in vivo).Deglycosylation experiments (endoglycosidase H(Endo H)) revealed distinct expression patterns for wild type hGAT-1 and the mutants: ER-resident proteins are core-glycosy