RADIOISOTOPIC INVESTIGATIONS OF ZINC UPTAKE INTO BRAIN SLICE

The presence of zinc in the vicinity of the hippocampal mossy fibers has been repeatedly demonstrated, and several lines of evidence suggest that the mossy-fiber zinc is concentrated within the terminals of mossy fibers. The specific function of the mossy-fiber zinc has not been established, athough neurotransmitter-related functions have been suggested (Storm-Mathisen, 1977, Prog. Neurobiol., 8: 119-181). In search of insight into the metabolism and function of mossy-fiber zinc, the present study investigated the transport of zinc into tissue slices and the response of the zinc transport to depolarization.;Kinetic analysis of zinc accumulation by mouse brain slices in vitro revealed the presence of a high affinity uptake component with an apparent Km of 17.7 (mu)M for hippocampus, 16.6 (mu)M for cortex and 25 (mu)M for striatum and a Vmax of 9.2 ng/mg/hr for the hippocampus, 10.1 ng/mg/hr for cortex and 9.6 ng/mg/hr for striatum (r > 0.99). The high affinity component was saturable as a function of substrate concentration and time, occurred against a concentration gradient, and was suppressed by cold (4(DEGREES)C) and ouabain. Depolarization of the tissue via elevated medium potassium increased the accumulation of zinc into hippocampal tissue.;Cytoarchitectonic differences in zinc transport between the different hippocampal subregions were found with those regions containing granule cells (dentate gyrus) or mossy fiber axons (hilus of the dentate gyrus and CA 3) accumulating greater amounts of zinc than the CA 1 region. Electrical stimulation (1.0-2.0 (mu)A/100 (mu)M('2), 12-25 P/sec) of the granule cells increased the specific uptake of zinc into all of the subregions, with the maximal increase occurring in the hilus of the dentate gyrus.;The present finding that mossy-fiber neuropil selectively accumulates zinc suggests the presence of a zinc-binding substance unique to mossy-fiber tissue. Selective augmentation of zinc uptake into mossy-fiber tissue by stimulation, moreover, suggests a possible neural-messenger role for mossy-fiber zinc.