Measuring D-serine efflux from mouse cortical brain slices using online microdialysis-capillary electrophoresis

Efflux of a number of important neurochemicals, including D-serine, L-serine, taurine, glutamate, and γ-aminobutyric acid (GABA), from mouse cortical brain slices housed in a 7 μL perfusion chamber was monitored using online microdialysis-CE (MD-CE). Analyte concentrations could be measured every 20-27 s using the MD-CE instrument. Stimulation with high potassium induced increased release of D-serine. Kainic acid (KA) induced D-serine release, but this release was not blocked by 6-cyano-7-nitroquinoxaline-2, 3-dione, suggesting that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid/KA receptors do not mediate D-serine release. Application of L-serine, the precursor of D-serine, resulted in increased extracellular D-serine concentrations. L-Cysteine also increased extracellular D-serine levels in a partially Na⁺-dependent manner. The observed effects upon application of L-serine and L-cysteine support the involvement of ASC neutral amino acid transporters in regulating the extracellular concentration of D-serine concentration through competitive inhibition of uptake or increased release through heteroexchange.