Pathologic concentrations of ammonium ions block l-glutamate uptake

Abstract

Both K+ and NH4+ are potent inhibitors of Na+-dependent l-glutamate binding to synaptic plasma membranes. Thus, the effects of these ions on Na+-dependent l-glutamate uptake were examined in rat forebrain synaptosome preparations. KCl (2 to 4 mM) stimulated l-glutamate uptake 34% over that in K+-free Krebs bicarbonate buffer; NH4+ was without effect. However, in the presence of 4 mM K+, NH4+ blocked the K+-stimulated component of Na+-dependent l-glutamate uptake. These effects were unrelated to ionic strength of Cl- as added Na+ or tris chloride had no effect on l-glutamate uptake. The results suggest that NH4+ could exert some of its toxic effects by blocking a specific l-glutamate uptake site, thereby elevating l-glutamate in the central nervous system. © 1985.