Ketamine (Ket) increased the amplitude of the tonic γ-aminobutyric acid (GABA) current. (A) Schematic diagram showing the experimental design. To mimic the tonic current generated in vivo, neurons were continuously perfused with a low concentration of GABA (0.3 μM), which generated a persistent inward current. The amplitude of the tonic current was quantified by applying the GABA receptor type A (GABA_A) receptor antagonist bicuculline (BIC, 20 μM) and measuring the change in holding current. Perfusion of ketamine, in the presence of GABA (0.3 μM), further increased the inward current as reflected by larger reduction in holding current when bicuculline was applied. (B) Representative traces demonstrating the dose-dependent enhancing effects of ketamine on tonic current. (C) Summarized data showing the dose-dependent effects of ketamine on the amplitude of the tonic current (n = 8 for each concentration). One-way repeated measures ANOVA, F(5,35) = 70.0, P < 0.0001; *P < 0.05, **P < 0.01, ***P < 0.001 versus 0 μM ketamine, Newman–Keuls post hoc test. (D) Quantified data showing that ketamine-induced increase in tonic current was decreased when GABA concentration was increased from 0.3 to 0.5 μM. Two-way ANOVA, effect of GABA concentration: F(1,49) = 35.1, P < 0.0001; effect of ketamine concentration: F(3,49) = 68.0, P < 0.0001; effect of interaction: F(3,49) = 0.7, P = 0.6; the numbers in the columns show the n number; no significance (N.S.), *P < 0.05, ***P < 0.001, Bonferroni post hoc test.