The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+ accumulation in rat hippocampus slices

3-Nitropropionic acid (3-NPA), a suicide inhibitor of succinate dehydrogenase (SDH; complex II), has been used to provide useful experimental models of Huntington's disease (HD) and "chemical hypoxia" in rodents. The trace ion Zn2+ has been shown to cause neurodegeneration. Employing real-time Newport Green fluorescence imaging of extracellular Zn2+, we found that 3-NPA (10-100 muM) caused a concentration-dependent increase in the concentration of extracellular Zn2+ ([Zn2+](o)) in acute rat hippocampus slices. This increase in [Zn2+](o) was abolished by 10 mM CaEDTA. The increase of [Zn2+](o) was also accompanied by a rapid increase of cytoplasmic-free Zn2+ concentration ([Zn2+](i)). The induction of Zn2+ release by 3-MPA in hippocampus slices points to a potential mechanism by which 3-NPA might induce neurodegeneration. (C) 2004 Elsevier Ireland Ltd. All rights reserved.