Effects of acute ethanol on the Ca2+ response to AMPA in cultured rat cortical GABAergic nonpyramidal neurons.
OBJECTIVE
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)-alpha-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 microm). 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 microm) 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.
Fischer
Wolfgang
W
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany. fisw@medizin.uni-leipzig.de
Franke
Heike
H
Illes
Peter
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium