Stimulated Efflux of Amino Acids and Glutathione from Cultured Hippocampal Slices by Omission of Extracellular Calcium

Malin H. Stridh, Mattias Tranberg, Stephen G. Weber, Fredrik Blomstrand, Mats Sandberg
2008 Journal of Biological Chemistry  
The extracellular neurochemistry determines normal brain function and the faith of neurons after insults such as stroke. This thesis concerns the effect of extracellular events related to intense neuronal stimulation and stroke, i.e. over-activation of glutamate-receptors and dramatically decreased extracellular Ca 2+ -concentrations, on efflux of neurotoxic and neuroprotective substances. The use of cultured slices of rat hippocampus enabled parallel analysis of efflux in combination with
more » ... mination of delayed nerve cell death after brief (5 min) overactivation of NMDA-receptors or omission of extracellular Ca 2+ for 15 min. Efflux by NMDA-receptor stimulation was selective and dominated by N-acetylaspartate, the antioxidant glutathione, phosphoethanolamine, taurine and hypotaurine. The efflux induced by concentration at and above 60 µM NMDA was paralleled by delayed neurotoxicity 24 h later. The efflux pathway is still unknown but does not appear to involve hemichannels, the Ca 2+ -calmodulin dependent kinase II or NO-synthesis.
doi:10.1074/jbc.m704153200 pmid:18272524 pmcid:PMC2447665 fatcat:gh6eih4n65a5reldv6no3fa3nm