TRICHLOROETHANOL POTENTIATION OF GAMMA-AMINOBUTYRIC ACID-ACTIVATED CHLORIDE CURRENT IN MOUSE HIPPOCAMPAL-NEURONS

1 The action of 2,2,2-trichloroethanol on gamma-aminobutyric acid (GABA)-activated Cl- current was studied in mouse hippocampal neurones in tissue culture by use of whole-cell patch-clamp recording. 2 Trichloroethanol increased the amplitude of currents activated by 1 mu M GABA or 0.1 mu M muscimol. Trichloroethanol, 1-25 mM, potentiated current activated by 1 mu M GABA in a concentration-dependent manner with an EC(50) of 3.0 +/- 1.4 mM and a maximal response (E(max)) of 576+/-72% of control. 3 Trichloroethanol potentiated currents activated by GABA concentrations <1O mu M, but did not increase the amplitude of currents activated by concentrations of GABA greater than or equal to 10 mu M. Despite marked potentiation of currents activated by low concentrations of GABA, trichloroethanol did not significantly alter the EC(50), slope, or E(max) of the GABA concentration-response curve. 4 Trichloroethanol, 5 mM, potentiated GABA-activated current in neurones in which ethanol, 10-500 mM, did not. The effect of trichloroethanol was not altered by the putative ethanol antagonist, Ro 15-4513. Trichloroethanol did not potentiate currents activated by pentobarbitone. 5 In the absence of exogenous GABA, trichloroethanol at concentrations greater than or equal to 2.5mM activated a current that appeared to be carried by Cl- as its reversal potential changed with changes in the Cl- gradient and as it was inhibited by the GABA(A) antagonists, bicuculline methiodide and picrotoxin. 6 Since trichloroethanol is thought to be the active metabolite of chloral hydrate and other chloral derivative anaesthetics, potentiation of the GABA-activated current in central nervous system neurones by trichloroethanol may contribute to the sedative/hypnotic effects of these agents.