The distribution and binding of zinc in the hippocampus.

Quantitative and qualitative studies suggest that zinc is concentrated in the mossy fiber boutons of the hippocampus and is believed to exist as a chelatable cytosolic pool. These studies were aimed at testing the hypothesis that a zinc-binding protein(s) or an amino acid pool in the cytosol is responsible for the sequestration of zinc. For comparison with the hippocampus, the cerebellum was chosen as a control region since it has been reported to contain lower levels of zinc both quantitatively and qualitatively. Initially, we confirmed that a quantitative difference in the levels of zinc exists between the hippocampus (12.59 +/- 0.85 micrograms of zinc/gm wet weight tissue, X +/- SD) and that this difference is reflected in cytosolic zinc levels. Using Ultrogel AcA 34 gel permeation chromatography, three major zinc-binding species were resolved. Two of these binding species appeared to account for most of the difference observed in the cytosolic levels of the two brain regions. Molecular weight criteria and differential pulse polarography behavior suggest that one of the species is a metallothionein-like protein. Based upon both molecular weight and ion exchange chromatography criteria, the other binding species may be a zinc-glutathione complex. There are no qualitative differences in the zinc-binding species localized in the cytosol of the hippocampus as compared with the cerebellum. However, the amount of binding species, in particular, the metallothionein-like protein and the putative zinc-glutathione complex, is greater in the hippocampus. These findings support the hypothesis that a cytosolic zinc-binding protein(s) may be responsible for the sequestration of zinc observed in the hippocampus.