Effects of acute ethanol on the Ca2+ response to AMPA in cultured rat cortical GABAergic nonpyramidal neurons

Abstract

Aims and Methods: Immunocytochemical studies revealed that the vast majority of neurons in our primary cultures of rat cortical cells are GABA-positive and represent nonpyramidal interneuron-like cells. The influence of ethanol on (S)-α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA -induced Ca2+ influx was investigated in multipolar, medium-sized neurons by using single-cell fura-2 microfluorimetry. Results: In a first series of experiments, the results showed a small but significant decrease of 17-22% by ethanol (100 mM) of the intracellular Ca2+ signals induced by slowly superfused AMPA (10, 30, 100 μm). This finding is comparable with the inhibitory activity of ethanol on N-methyl-D-aspartic acid (NMDA)-induced Ca2+ signals in these cells. Further studies with a fast pressure-application of AMPA (30 μM) showed a similar degree of inhibition by ethanol (100 mM). Superfusion with tetrodotoxin/bicuculline, to rule out possible effects of spontaneously released GABA and synaptic spike activity, did not significantly influence the AMPA-induced Ca2+ response nor the inhibitory effect of ethanol. Conclusions: The present findings indicate that ethanol at high concentrations inhibits Ca2+ signaling via both AMPA and NMDA glutamate receptors in cortical interneuron-like cells. These effects may contribute to the central depressant action of this drug.