Fig. 3.
Isoflurane regulates γ-aminobutyric acid type-A (GABAA) receptor activity through a complex mechanism. (A) Traces of GABA-evoked current (IGABA) recorded in the same A549 cell depicts the complex effects of various concentrations of isoflurane (ISO; concentrations given in µm) on GABAA receptor activity evoked by low (0.5 µm), moderate (10 µm), and high (100 µm) concentrations of GABA. Isoflurane dose dependently enhanced IGABA, with lesser degree of enhancement on the current evoked by a higher concentration of GABA. When the isoflurane concentration was high, termination of isoflurane caused a rebound of IGABA. (B) Plots show the degree of dose-dependent enhancement by different concentrations of isoflurane (0.83–83.3 μm) of IGABA evoked by 0.5 μm GABA (IGABA0.5, circle) or 10 μm GABA (IGABA10, square). The largest amplitude of IGABA in the presence of isoflurane was normalized to the amplitude of IGABA recorded 20 ms before application of isoflurane. (C) Shown are characteristic traces of IGABA recorded from the same cell, illustrating that 250 μm isoflurane enhanced the current evoked by 0.5 μm GABA (C-1) but inhibited the current evoked by 100 μm GABA (C-2). (D) Shown are traces of IGABA (evoked by 10 μm GABA) recorded from the same cell, illustrating the effect of sevoflurane on IGABA. GABA was co-applied during perfusion of sevoflurane. Note that low concentration (1:1000) of sevoflurane enhanced IGABA (D-1) but high concentration (1:10) of sevoflurane decreased IGABA (D-2).