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Trichloroethanol potentiation of γ‐aminobutyric acid‐activated chloride current in mouse hippocampal neurones
Author(s) -
Peoples Robert W.,
Weight Forrest F.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17025.x
Subject(s) - chemistry , picrotoxin , chloral hydrate , muscimol , long term potentiation , bicuculline , gabaa receptor , nipecotic acid , patch clamp , gamma aminobutyric acid , aminobutyric acid , antagonist , biophysics , biochemistry , pharmacology , neurotransmitter , receptor , biology
1 The action of 2,2,2‐trichloroethanol on γ‐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 μ m GABA or 0.1 μ m muscimol. Trichloroethanol, 1–25 m m , potentiated current activated by 1 μ m GABA in a concentration‐dependent manner with an EC 50 of 3.0 ± 1.4 m m and a maximal response ( E max ) of 576 ± 72% of control. 3 Trichloroethanol potentiated currents activated by GABA concentrations < 10 μ m , but did not increase the amplitude of currents activated by concentrations of GABA ≥ 10 μ 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, 5mM, potentiated GABA‐activated current in neurones in which ethanol, 10–500 m m , 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 ≥ 2.5 m m 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.