Pathologic concentrations of ammonium ions block L-glutamate uptake

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.