MILD EXTERNAL ACIDOSIS ATTENUATES THE KAI NATE-INDUCED NEUROCYTOTOXICDAMAGE OF CULTURED CEREBELLAR GRANULE CELLS

This work continues our previous studies on the possible involvement o f Na+/H+ exchanger in the mechanisms of neurocytotoxic action of excit atory amino acids on cultured cerebellar qranule cells. The 7-8-day-ol d cultures were exposed to 100 mN kainate for 30 min in salt solution at pH 7.6-7.8 or at pH 6.7-6.8. A specific NMDA receptor antagonist D, L-2-amino-5-phosphonovalerate (APV, 1 mM) was added to all kainate-con taining solutions in order to avoid the possible autocoid stimulation of NMDA receptors by endogenous glutamate which could be released from kainate-treated neurons. Cell death was estimated morphologically 4 h after the termination of kainate treatment. At pH 7.6 kainate induced an irreversible damage of about 60% of cells, whereas at pH 6.8 this value did not exceed 35%. The protective effect of pH lowering on nerv e cells treated with kainate cannot be explained by H+ blockade of kai nate receptor channels since the latter, in contrast to NMDA channels, are relatively resistant to mild external acidosis. Therefore, we int erpret the results obtained as evidence of the involvement of Na+/H+ e xchange in neurotoxic action of kainate.