Ethanol enhances GABA-induced ³⁶Cl-influx in primary spinal cord cultured neurons

Ethanol has a pharmacological profile similar to other centrally acting drugs, which facilitate GABAergic transmission. GABA is known to produce its effects by increasing the conductance to Cl^- ions. In this study, we have examined the effect of ethanol on GABA-induced ³⁶Cl-influx in primary spinal cord cultured neurons. GABA produces a concentration-dependent and saturable effect on ³⁶Cl-influx in these neurons. Ethanol potentiates the effect of GABA on ³⁶Cl-influx in these neurons. GABA (20 μM) increased the ³⁶Cl-influx by 75% over the basal value and in the presence of 50 mM ethanol, the observed increase was 142%. Eadie-Hoffstee analysis of the saturation curves indicated that ethanol decreases the K_m value of GABA (10.6 μM to 4.2 μM) and also increases the V_max. Besides potentiating the effect of GABA, ethanol also appears to have a direct effect in the absence of added GABA. These results suggest that ethanol enhances GABA-induced ³⁶Cl-influx and indicate a role of GABAergic system in the actions of ethanol. These results also support the behavioral and electrophysiological studies, which have implicated GABA systems in the actions of ethanol. The potential mechanism(s) and the role of direct effect of ethanol is not clear at this time, but is currently being investigated.