Pathologic concentrations of ammonium ions block l-glutamate uptake

Abstract

Both K + and NH 4 + 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 m M) stimulated l-glutamate uptake 34% over that in K +-free Krebs bicarbonate buffer; NH 4 + was without effect. However, in the presence of 4 m M K +, NH 4 + 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 NH 4 + could exert some of its toxic effects by blocking a specific l-glutamate uptake site, thereby elevating l-glutamate in the central nervous system.