THE INHIBITOR OF NA+ H+ EXCHANGE - ETHYLI SOPROPYL AMILORIDE DECREASES CALCIUM OVERLOAD IN NEURONS DURING THE POSTGLUTAMATE PERIOD/

Dynamics of intracellular free Ca2+ ([Ca2+]i) was monitored in single cerebellar granule cells and hippocampal neurons using the fluorescent probe Fura 2/AM and a Spex spectrofluorimeter. It is known that a sta ble postglutamate elevation of [Ca2+]i is resistant to the blockers of voltage-sensitive Ca2+ channels and antagonists of glutamate receptor s. The present experiments have shown that application of the quaterna ry derivative of lidocaine, QX 314 (2 mM), or a two-fold increase in t he osmolarity of external salt solution (280 mM sucrose) in the postgl utamate period were also unable to decrease [Ca2+]i. The only drug whi ch proved to be capable of inducing a consistent decrease in [Ca2+]i i n the postglutamate period was ethylisopropyl amiloridae (EIPA, 20 muM known as a potent inhibitor of Na+/H+ exchange. This effect of EIPA c annot be explained by its direct blocking action on NMDA channels sinc e a spicific NMDA antagonist DL-2-amino-5-phosphonovalerate (APV, 1 mM ), when applied in the postglutamate period. fails to decrease [Ca2+]i or protect cerebellar granule cells from a delated glutamate neurotox icity. The data obtained suggest a significant role of the Na+/H+ exch ange system in destabilization of Ca2+ homeostasis after toxic glutama te treatment.