The protective role of mild acidic pH shifts on synaptic NMDA current in hippocampal slices.

Glutamate is a major neurotransmitter in the CNS. Its release activates NMDA and non-NMDA receptors on the postsynaptic membrane. NMDA receptor activation is shown to be important in physiological and pathological events. The modulatory sites on the NMDA receptor-channel ionophore complex are important in the regulation of the channel's cation conductance. Regulation of the channel by proton concentration may be important in the alkalinization that occurs during the normal release of glutamate or in the acidification that occurs during hypoxia/ischemia. In this study, the selective downregulation of the NMDA channel with slight extracellular pH changes and reversibility of this modulation have been shown in hippocampal slices. It has also been shown that hippocampal slices are more responsive to pH changes than other experimental preparations. The downregulation of the NMDA current may represent a native control mechanism. Direct and indirect modulation caused by extracellular pH changes on the NMDA receptor ionophore complex might be important in the overall response of the neuron under pathophysiological changes. Copyright 1998 Elsevier Science B.V.