Ethanol inhibits NMDA-induced increases in free intracellular Ca2+ in dissociated brain cells.

The effect of N-methyl-D-aspartate (NMDA) on free intracellular Ca2+ concentrations [( Ca2+]i) and the interaction of ethanol on the NMDA-mediated response was examined in freshly dissociated brain cells isolated from newborn rats. NMDA (25 microM) increased [Ca2+]i by approximately 70 nM, measured by fura-2 fluorometry, and this increase could be prevented or reversed by the NMDA antagonists Mg2+ (1.0 mM) and 2-amino-5-phosphonovalerate (AP5, 100 microM). Ethanol (25, 50, 100 mM) added 50 s before NMDA (25 microM) reduced the rise in [Ca2+]i when compared to the 25 microM NMDA response in the absence of ethanol. Thus, ethanol may have direct actions on NMDA-receptor activated increases in [Ca2+]i.