INTERACTIVE EFFECTS OF PH AND TEMPERATURE ON N-METHYL-D-ASPARTATE RECEPTOR ACTIVITY IN RAT CORTICAL BRAIN-SLICES

Low extracellular pH decreases the activity of the N-methyl-D-aspartat e (NMDA) glutamate receptor. and may thus limit neuronal calcium overl oad during cerebral ischemia. During induced hypothermia, alkaline pH (''alphastat regulation'') is often used to preserve cardiac and enzym atic function. The purpose of this study is to measure the functional activity of cerebral cortex NMDA receptors over the range of temperatu res used in profound hypothermic cardiopulmonary bypass (20-37 degrees C). Extracellular pH was varied aver a broad range relevant to both a lphastat and pH stat acid-base management (7.0-7.8). Change in cytosol ic free calcium evoked by 50 mu M NMDA in brain slices tvas used as an index of NMDA receptor activity, Cortical slices (300 mu m thick) wer e loaded with fura-2 Aspartate Methyl for study in a fluorometer. At 3 7 degrees C, a change in extracellular pH from 7.1 to 7.8 increased th e NMDA-evoked change in cytosolic calcium in brain slices by a factor of 4 (p < 0.05). In contrast, at 20 degrees C there was minimal effect of changing extracellular pH from 7.1 to 7.8 (27% increase), We concl ude that hypothermia results in decreased pH sensitivity of the NMDA r eceptor. The results predict that different strategies of pH managemen t during induced hypothermia may have limited impact on NMDA receptor- mediated processes, such as neuronal calcium overload.